Crosstalk between HIV and hepatitis C virus during co-infection

An estimated one-third of individuals positive for HIV are also infected with hepatitis C virus (HCV). Chronic infection with HCV can lead to serious liver disease including cirrhosis and hepatocellular carcinoma. Liver-related disease is among the leading causes of death in patients with HIV, and individuals with HIV and HCV co-infection are found to progress more rapidly to serious liver disease than mono-infected individuals. The mechanism by which HIV affects HCV infection in the absence of immunosuppression by HIV is currently unknown. In a recent article published in BMC Immunology, Qu et al. demonstrated that HIV tat is capable of inducing IP-10 expression. Further, they were able to show that HIV tat, when added to cells, was able to enhance the replication of HCV. Importantly, the increase in HCV replication by tat was found to be dependent on IP-10. This work has important implications for understanding the effect HIV has on the outcome of HCV infection in co-infected individuals. The findings of Qu et al. may inform the design of intervention and treatment strategies for co-infected individuals

Cause-Specific Excess Mortality in Siblings of Patients Co-Infected with HIV and Hepatitis C Virus

BACKGROUND: Co-infection with hepatitis C in HIV-infected individuals is associated with 3- to 4-fold higher mortality among these patients' siblings, compared with siblings of mono-infected HIV-patients or population controls. This indicates that risk factors shared by family members partially account for the excess mortality of HIV/HCV-co-infected patients. We aimed to explore the causes of death contributing to the excess sibling mortality. METHODOLOGY AND PRINCIPAL FINDINGS: We retrieved causes of death from the Danish National Registry of Deaths and estimated cause-specific excess mortality rates (EMR) for siblings of HIV/HCV-co-infected individuals (n = 436) and siblings of HIV mono-infected individuals (n = 1837) compared with siblings of population controls (n = 281,221). Siblings of HIV/HCV-co-infected individuals had an all-cause EMR of 3.03 (95% CI, 1.56-4.50) per 1,000 person-years, compared with siblings of matched population controls. Substance abuse-related deaths contributed most to the elevated mortality among siblings [EMR = 2.25 (1.09-3.40)] followed by unnatural deaths [EMR = 0.67 (-0.05-1.39)]. No siblings of HIV/HCV co-infected patients had a liver-related diagnosis as underlying cause of death. Siblings of HIV-mono-infected individuals had an all-cause EMR of 0.60 (0.16-1.05) compared with siblings of controls. This modest excess mortality was due to deaths from an unknown cause [EMR = 0.28 (0.07-0.48)], deaths from substance abuse [EMR = 0.19 (-0.04-0.43)], and unnatural deaths [EMR = 0.18 (-0.06-0.42)]. CONCLUSIONS: HCV co-infection among HIV-infected patients was a strong marker for family-related mortality due to substance abuse and other unnatural causes. To reduce morbidity and mortality in HIV/HCV-co-infected patients, the advances in antiviral treatment of HCV should be accompanied by continued focus on interventions targeted at substance abuse-related risk factors

Within-Host Dynamics of the Hepatitis C Virus Quasispecies Population in HIV-1/HCV Coinfected Patients

HIV/HCV coinfected individuals under highly active antiretroviral therapy (HAART) represent an interesting model for the investigation of the role played by the immune system in driving the evolution of the HCV quasispecies. We prospectively studied the intra-host evolution of the HCV heterogeneity in 8 coinfected subjects, selected from a cohort of 32 patients initiating HAART: 5 immunological responders (group A) and 3 immunological non-responders (group B), and in two HCV singly infected controls not assuming drugs (group C). For all these subjects at least two serial samples obtained at the first observation (before HAART) and more than 1 year later, underwent clonal sequence analysis of partial E1/E2 sequences, encompassing the whole HVR1. Evolutionary rates, dated phylogenies and population dynamics were co-estimated by using a Bayesian Markov Chain Monte Carlo approach, and site specific selection pressures were estimated by maximum likelihood-based methods. The intra-host evolutionary rates of HCV quasispecies was 10 times higher in subjects treated with HAART than in controls without immunodeficiency (1.9 and 2.3×10−3 sub/site/month in group A and B and 0.29×10−3 sub/site/month in group C individuals). The within-host Bayesian Skyline plot analysis showed an exponential growth of the quasispecies populations in immunological responders, coinciding with a peak in CD4 cell counts. On the contrary, quasispecies population remained constant in group B and in group C controls. A significant positive selection pressure was detected in a half of the patients under HAART and in none of the group C controls. Several sites under significant positive selection were described, mainly included in the HVR1. Our data indicate that different forces, in addition to the selection pressure, drive an exceptionally fast evolution of HCV during HAART immune restoration. We hypothesize that an important role is played by the enlargement of the viral replicative space

ATP release during cell swelling activates a Ca2+-dependent Cl - Current by autocrine mechanism in mouse hippocampal microglia

Microglia cells, resident immune cells of the brain, survey brain parenchyma by dynamically extending and retracting their processes. Cl- channels, activated in the cellular response to stretch/swelling, take part in several functions deeply connected with microglia physiology, including cell shape changes, proliferation, differentiation and migration. However, the molecular identity and functional properties of these Cl- channels are largely unknown. We investigated the properties of swelling-activated currents in microglial from acute hippocampal slices of Cx3cr1+/GFP mice by whole-cell patch-clamp and imaging techniques. The exposure of cells to a mild hypotonic medium, caused an outward rectifying current, developing in 5-10 minutes and reverting upon stimulus washout. This current, required for microglia ability to extend processes towards a damage signal, was carried mainly by Cl- ions and dependent on intracellular Ca2+. Moreover, it involved swelling-induced ATP release. We identified a purine-dependent mechanism, likely constituting an amplification pathway of current activation: under hypotonic conditions, ATP release triggered the Ca2+-dependent activation of anionic channels by autocrine purine receptors stimulation. Our study on native microglia describes for the first time the functional properties of stretch/swelling-activated currents, representing a key element in microglia ability to monitor the brain parenchyma

Identification services for online social networks (OSNs) extended abstract

On-line Social Networks (OSNs) have dramatically changed how users connect, communicate, share content, and exchange goods and services. However, despite all the benefits and the flexibility that OSNs provide, their users become more reliant on online identities with often no means to know who really is behind an online profile. Indeed, to facilitate their adoption and encourage people to join, identities in OSNs are very loose, in that not much more than an email address is required to create an account and related profile. Therefore, the problem of fake accounts and identity related attacks in OSNs has attracted considerable interest from the research community, and resulted in several proposals that mainly aim at detecting malicious nodes that follow identified and formalized attack trends. Without denying the importance of formalizing Sybil attacks and suggesting solutions for their detection, in this extended abstract we also consider the issue of identity validation from a user perspective, by briefly discussing the research proposals aiming at empowering users with tools helping them to identify the validity of the online accounts they interact with

Zn1-xGdxS (x=0.1, 0.2 and 0.3) nanoparticles for magnetic resonance imaging and optical fluorescence imaging

This work proposes chemically synthesized Gd doped ZnS nanoparticles based system for potential use as contrast enhancing agent for both optical fluorescence imaging and magnetic resonance imaging. Two different Gd doped ZnS nanoparticle systems were synthesized. These systems were (i) graphene oxide-Zn1-xGdxS (x = 0.1, 0.2 and 0.3) nanoparticle composites and (ii) chitosan coated Zn1-xGdxS (x = 0.1, 0.2 and 0.3) nanoparticles. Gd formed solid solution with ZnS in all the six as-synthesized samples. Gd doped ZnS nanoparticles in both cases exhibited both longitudinal and transverse relaxivity values. A clear dependence the relaxivity values on the composition of the nanoparticles and the nanoparticle environment (presence and absence of graphene oxide) was observed. Between the two cases, values of the longitudinal and transverse relaxivity were higher for the graphene oxide-Zn1-xGdxS composites. It is also shown that Gd doped ZnS nanoparticle can be used for fluorescence imaging also. Gd doped ZnS nanoparticle exhibited biocompatibility towards the MCF-7 cell line

Effect of core-shell nanoparticle geometry on the enhancement of the proton relaxivity value in a nuclear magnetic resonance experiment

This work illustrates the effect of core-shell nanoparticle geometry on the enhancement of the proton relaxivity value in a nuclear magnetic resonance experiment. Chemically synthesized CoFe2O4-MnFe2O4 core-shell nanoparticles were chosen as a candidate material. A two step methodology was used to synthesize the core-shell nanoparticles. In the first step, CoFe2O4 seed nanoparticles were synthesized and in the second step a MnFe2O4 phase was grown over seed CoFe2O4 nanoparticles to form the core-shell geometry. Characterization of the as-synthesized nanoparticles by diffraction methods, electron microscopy and X-ray photoelectron spectroscopy confirmed the formation of uniform core-shell nanoparticles. Magnetic measurement revealed the superparamagnetic nature of the as-synthesized core-shell nanoparticles. The transverse proton relaxivity values obtained by the nuclear magnetic resonance experiment conducted at room temperature using a field of 9.4 T in the presence of single phase CoFe2O4, MnFe2O4 and CoFe2O4-MnFe2O4 core-shell nanoparticles were 60.9 mM(-1) s(-1), 83.2 mM(-1) s(-1) and 194.8 mM(-1) s(-1) respectively. This result clearly illustrated that a greater magnetic inhomogeneity induced in the medium surrounding the core-shell nanoparticles containing two different magnetic phases yields the highest value for the transverse proton relaxivity

Graphene oxide-Fe3O4 nanoparticle composite with high transverse proton relaxivity value for magnetic resonance imaging

The potential of graphene oxide-Fe3O4 nanoparticle (GO-Fe3O4) composite as an image contrast enhancing material in magnetic resonance imaging has been investigated. Proton relaxivity values were obtained in three different homogeneous dispersions of GO-Fe3O4 composites synthesized by precipitating Fe3O4 nanoparticles in three different reaction mixtures containing 0.01 g, 0.1 g, and 0.2 g of graphene oxide. A noticeable difference in proton relaxivity values was observed between the three cases. A comprehensive structural and magnetic characterization revealed discrete differences in the extent of reduction of the graphene oxide and spacing between the graphene oxide sheets in the three composites. The GO-Fe3O4 composite framework that contained graphene oxide with least extent of reduction of the carboxyl groups and largest spacing between the graphene oxide sheets provided the optimum structure for yielding a very high transverse proton relaxivity value. It was found that the GO-Fe3O4 composites possessed good biocompatibility with normal cell lines, whereas they exhibited considerable toxicity towards breast cancer cells. (C) 2015 AIP Publishing LLC

A chemo-enzymatic route to diastereoisomers of 2-methyl-1-phenyl-1,3-butanediol: the dual role of microorganisms

Diastereoisomers (1S,2R,3S)-, (1R,2R,3S)-, (1R,2S,3S)- and (1S,2S,3S)-2-methyl-1-phenyl-1,3-butanediols were prepared by simple and convenient strategies using two different chemo-enzymatic approaches for the reduction of racemic 2-methyl-1-phenyl-1,3-butanedione,both involving in situ racemization. The first method comprised a one-pot microbial reduction coupled with a chemical reduction, while in the second method, stepwise chemo-enzymatic reductions were performed