Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis

Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3

Rethinking the British World

Copyright @ 2013 The North American Conference on British StudiesThis article rethinks the concept of the “British World” by paying close attention to the voices of those who attended the 1903 Allied Colonial Universities Conference. They identified not one, but three different kinds of British world space. Mapped, respectively, by ideas and emotions, by networks and exchange, and by the specific sites of empire, this article suggests that, in the light of criticisms the British World concept has faced, and in the context of recent scholarship on the social and material production of space, this tripartite approach might offer a useful framework for British and imperial historians interested in the history of the global

Governance and sustainability in Glasgow: connecting symbolic capital and housing consumption to regeneration

To transcend a legacy of slum-living, paternalistic provision and urban decline, Glasgow City Council has endeavoured to transform the city's fortunes by a plethora of mechanisms that have at their core the establishment of sustainable communities. Framed within a policy discourse which emphasises 'cultural and social' as well as 'physical and economic' renaissance, the crux of the Council's strategy has been to stem the migratory tide of affluent households and to empower public sector housing tenants. Drawing on Rose's 'ethopolitics' we argue these developments in Glasgow reflect the wider emergence of technologies of governance in UK housing policy that seek to realign citizens' identities with norms of active, entrepreneurial consumption

Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis

Background: Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. Aims: We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. Methods: We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. Results: HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. Conclusions: We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3

Not poles apart: Antarctic soil fungal communities show similarities to those of the distant Arctic

Antarctica's extreme environment and geographical isolation offers a useful platform for testing the relative roles of environmental selection and dispersal barriers influencing fungal communities. The former process should lead to convergence in community composition with other cold environments, such as those in the Arctic. Alternatively, dispersal limitations should minimise similarity between Antarctica and distant northern landmasses. Using high-throughput sequencing, we show that Antarctica shares significantly more fungi with the Arctic, and more fungi display a bipolar distribution, than would be expected in the absence of environmental filtering. In contrast to temperate and tropical regions, there is relatively little endemism, and a strongly bimodal distribution of range sizes. Increasing southerly latitude is associated with lower endemism and communities increasingly dominated by fungi with widespread ranges. These results suggest that micro-organisms with well-developed dispersal capabilities can inhabit opposite poles of the Earth, and dominate extreme environments over specialised local specie

A First Look at Galaxy Flyby Interactions: I. Characterizing the Frequency of Flybys in a Cosmological Context

Hierarchical structure formation theory is based on the notion that mergers drive galaxy evolution, so a considerable framework of semi-analytic models and N-body simulations has been constructed to calculate how mergers transform a growing galaxy. However, galaxy mergers are only one type of major dynamical interaction between halos -- another class of encounter, a close flyby, has been largely ignored. We use cosmological N-body simulations to reconstruct the entire dynamical interaction history of dark matter halos. We present a careful method of identifying and tracking a dark matter halo which resolves the typical classes of anomalies that occur in N-body data. This technique allows us to robustly follow halos and several hierarchical levels of subhalos as they grow, dissolve, merge, and flyby one another -- thereby constructing both a census of the dynamical interactions in a volume and an archive of the dynamical evolution of an individual halo. In addition to a census of mergers, our tool characterizes the frequency of close flyby interactions in the Universe. We find that the number of close flyby interactions is comparable to, or even surpasses, the number of mergers for halo masses \gtrsim 10^{11}\,\Msun at $z \lesssim 2$. Halo flybys occur so frequently to high mass halos that they are continually perturbed, unable to reach a dynamical equilibrium. In particular, we find that Milky Way type halos undergo a similar number of flybys as mergers irrespective of mass-ratio for $z\lesssim 2$. We also find tentative evidence that at high redshift, $z \gtrsim 14$, flybys are as frequent as mergers. Our results suggest that close halo flybys can play an important role in the evolution of the earliest dark matter halos and their galaxies, and can still influence galaxy evolution at the present epoch. [Abridged]Comment: Replaced to match version accepted to ApJ. Figure resolution degraded for arXiv limits, full resolution paper available at http://astro.phy.vanderbilt.edu/~sinham/research.htm

PCSK9, apolipoprotein E and lipoviral particles in chronic hepatitis C genotype 3: evidence for genotype-specific regulation of lipoprotein metabolism.

BACKGROUND & AIMS: Hepatitis C virus (HCV) associates with lipoproteins to form "lipoviral particles" (LVPs) that can facilitate viral entry into hepatocytes. Initial attachment occurs via heparan sulphate proteoglycans and low-density lipoprotein receptor (LDLR); CD81 then mediates a post-attachment event. Proprotein convertase subtilisin kexin type 9 (PCSK9) enhances the degradation of the LDLR and modulates liver CD81 levels. We measured LVP and PCSK9 in patients chronically infected with HCV genotype (G)3. PCSK9 concentrations were also measured in HCV-G1 to indirectly examine the role of LDLR in LVP clearance. METHODS: HCV RNA, LVP (d1.07g/ml) fractions, were quantified in patients with HCV-G3 (n=39) by real time RT-PCR and LVP ratios (LVPr; LVP/(LVP+non-LVP)) were calculated. Insulin resistance (IR) was assessed using the homeostasis model assessment of IR (HOMA-IR). Plasma PCSK9 concentrations were measured by ELISA in HCV-G3 and HCV-G1 (n=51). RESULTS: In HCV-G3 LVP load correlated inversely with HDL-C (r=-0.421; p=0.008), and apoE (r=-0.428; p=0.013). The LVPr varied more than 35-fold (median 0.286; range 0.027 to 0.969); PCSK9 was the strongest negative predictor of LVPr (R(2)=16.2%; p=0.012). HOMA-IR was not associated with LVP load or LVPr. PCSK9 concentrations were significantly lower in HCV-G3 compared to HCV-G1 (p<0.001). PCSK9 did not correlate with LDL-C in HCV-G3 or G1. CONCLUSIONS: The inverse correlation of LVP with apoE in HCV-G3, compared to the reverse in HCV-G1 suggests HCV genotype-specific differences in apoE mediated viral entry. Lower PCSK9 and LDL concentrations imply upregulated LDLR activity in HCV-G3

The Environments of Local Luminous Infrared Galaxies: Star Formation Rates increase with Density

This work studies the environments and star formation relationships of local luminous infrared galaxies (LIRG) in comparison to other types of local and distant (z~1) galaxies. The infrared (IR) galaxies are drawn from the IRAS sample. The density of the environment is quantified using 6dF and Point Source Catalogue redshift survey (PSCz) galaxies in a cylinder of 2h^-1 Mpc radius and 10h^-1 Mpc length. Our most important result shows the existence of a dramatic density difference between local LIRGs and local non-LIRG IR galaxies. LIRGs live in denser environments than non-LIRG IR galaxies implying that L_IR=10^11 h^-2 L_sun marks an important transition point among IR-selected local galaxies. We also find that there is a strong correlation between the densities around LIRGs and their L_IR luminosity, while the IR-activity of non-LIRG IR galaxies does not show any dependence on environment. This trend is independent of mass-bin selection. The SF-density trend in local LIRGs is similar to that found in some studies of blue cloud galaxies at z~1 which show a correlation between star formation and local density (the reversal of the relation seen for local galaxies). This, together with the rapid decline of the number count of LIRGs since z~1, could mean that local LIRGs are survivors of whatever process transformed blue cloud galaxies at z~1 to the present day or local LIRGs came into existence by similar process than high redshift LIRGs but at later stage.Comment: 13 pages with 6 figures. Discussion expanded and references added to match accepted MNRAS version, results unchange