Susceptible and Protective HLA Class 1 Alleles against Dengue Fever and Dengue Hemorrhagic Fever Patients in a Malaysian Population

BACKGROUND: The human leukocyte antigen alleles have been implicated as probable genetic markers in predicting the susceptibility and/or protection to severe manifestations of dengue virus (DENV) infection. In this present study, we aimed to investigate for the first time, the genotype variants of HLA Class 1(-A and -B) of DENV infected patients against healthy individuals in Malaysia. METHODOLOGY/PRINCIPAL FINDINGS: This study was carried out with 92 dengue disease patients and 95 healthy controls from three different ethnic groups (Malay, Chinese and Indian) in Malaysia. All patients with clinical and laboratory confirmation of DENV infection were typed for the HLA-A and B loci, using polymerase chain reaction-sequence specific primer techniques. In our total population, a significant increase for HLA-B*53 (P = 0.042, Pc = 1.008) allele and a significant decrease for A*03 (P = 0.015, Pc = 0.18, OR = 5.23, 95% CI = 1.19-23.02) and B*18 (P = 0.017, Pc = 0.408) alleles were noted in DHF patients as compared to healthy donors. We also observed that in the Malay DHF patients, allele B*13 (P = 0.049, Pc = 1.176, OR = 0.18, 95% CI = 0.03-0.90) was present at a significantly higher frequency in this population while allele HLA-B*18 (P = 0.024, Pc = 0.576) was seen to be negatively associated with DHF. CONCLUSIONS/SIGNIFICANCE: These are the first findings on genetic polymorphisms in our population and we conclude that: (1) In our total population, HLA-B*53 probably involve in disease susceptibility, while the HLA-A*03 and HLA-B*18 may confer protection from progression to severe disease; (2) In the Malay population, HLA-B*13 and B*18 are probably associated in disease susceptibility and protection, respectively. These results could furnish as a valuable predictive tool to identify ethnically different individuals at risk and/or protection from severe forms of DENV infection and would provide valuable informations for the design of future dengue vaccine

Instabilities and the roton spectrum of a quasi-1D Bose-Einstein condensed gas with dipole-dipole interactions

We point out the possibility of having a roton-type excitation spectrum in a quasi-1D Bose-Einstein condensate with dipole-dipole interactions. Normally such a system is quite unstable due to the attractive portion of the dipolar interaction. However, by reversing the sign of the dipolar interaction using either a rotating magnetic field or a laser with circular polarization, a stable cigar-shaped configuration can be achieved whose spectrum contains a `roton' minimum analogous to that found in helium II. Dipolar gases also offer the exciting prospect to tune the depth of this `roton' minimum by directly controlling the interparticle interaction strength. When the minimum touches the zero-energy axis the system is once again unstable, possibly to the formation of a density wave.Comment: 7 pages, 6 figures. Special Issue: "Ultracold Polar Molecules: Formation and Collisions

Aedes aegypti Saliva Alters Leukocyte Recruitment and Cytokine Signaling by Antigen-Presenting Cells during West Nile Virus Infection

West Nile virus (WNV) is transmitted during mosquito bloodfeeding. Consequently, the first vertebrate cells to contact WNV are cells in the skin, followed by those in the draining lymph node. Macrophages and dendritic cells are critical early responders in host defense against WNV infection, not just because of their role in orchestrating the immune response, but also because of their importance as sites of early peripheral viral replication. Antigen-presenting cell (APC) signals have a profound effect on host antiviral responses and disease severity. During transmission, WNV is intimately associated with mosquito saliva. Due to the ability of mosquito saliva to affect inflammation and immune responses, and the importance of understanding early events in WNV infection, we investigated whether mosquito saliva alters APC signaling during arbovirus infection, and if alterations in cell recruitment occur when WNV infection is initiated with mosquito saliva. Accordingly, experiments were performed with cultured dendritic cells and macrophages, flow cytometry was used to characterize infiltrating cell types in the skin and lymph nodes during early infection, and real-time RT-PCR was employed to evaluate virus and cytokine levels. Our in vitro results suggest that mosquito saliva significantly decreases the expression of interferon-β and inducible nitric oxide synthase in macrophages (by as much as 50 and 70%, respectively), whilst transiently enhancing interleukin-10 (IL-10) expression. In vivo results indicate that the predominate effect of mosquito feeding is to significantly reduce the recruitment of T cells, leading the inoculation site of mice exposed to WNV alone to have up to 2.8 fold more t cells as mice infected in the presence of mosquito saliva. These shifts in cell population are associated with significantly elevated IL-10 and WNV (up to 4.0 and 10 fold, respectively) in the skin and draining lymph nodes. These results suggest that mosquito saliva dysregulates APC antiviral signaling, and reveal a possible mechanism for the observed enhancement of WNV disease mediated by mosquito saliva via a reduction of T lymphocyte and antiviral activity at the inoculation site, an elevated abundance of susceptible cell types, and a concomitant increase in immunoregulatory activity of IL-10

Effect of quantum group invariance on trapped Fermi gases

We study the properties of a thermodynamic system having the symmetry of a quantum group and interacting with a harmonic potential. We calculate the dependence of the chemical potential, heat capacity and spatial distribution of the gas on the quantum group parameter $q$ and the number of spatial dimensions $D$. In addition, we consider a fourth-order interaction in the quantum group fields $\Psi$, and calculate the ground state energy up to first order.Comment: LaTeX file, 20 pages, four figures, uses epsf.sty, packaged as a single tar.gz uuencoded fil

Momentum flux density, kinetic energy density and their fluctuations for one-dimensional confined gases of non-interacting fermions

We present a Green's function method for the evaluation of the particle density profile and of the higher moments of the one-body density matrix in a mesoscopic system of N Fermi particles moving independently in a linear potential. The usefulness of the method is illustrated by applications to a Fermi gas confined in a harmonic potential well, for which we evaluate the momentum flux and kinetic energy densities as well as their quantal mean-square fluctuations. We also study some properties of the kinetic energy functional E_{kin}[n(x)] in the same system. Whereas a local approximation to the kinetic energy density yields a multi-valued function, an exact single-valued relationship between the density derivative of E_{kin}[n(x)] and the particle density n(x) is demonstrated and evaluated for various values of the number of particles in the system.Comment: 10 pages, 5 figure

Prospective Study of Chikungunya Virus Acute Infection in the Island of La Réunion during the 2005–2006 Outbreak

BACKGROUND:Chikungunya virus (CHIKV) is a recently re-emerged arthropod borne virus responsible for a massive outbreak in the Indian Ocean and India, and extended to Southeast Asia as well as Italy. CHIKV has adapted to Aedes albopictus, an anthropophilic mosquito species widely distributed in Asia, Europe, Africa and America. Our objective was to determine the clinical and biological features of patients at the acute phase of CHIKV infection. METHODS AND FINDINGS:A prospective study enrolled 274 consecutive patients with febrile arthralgia recorded at the Emergency Department of the Groupe Hospitalier Sud-Réunion between March and May 2006. Three groups were defined: one group of 180 viremic patients (positive CHIKV RT-PCR), one group of 34 patients with acute post-viremic infection (negative CHIKV RT-PCR, positive anti-CHIKV IgM and negative IgG), and one group of 46 uninfected patients (negative CHIKV RT-PCR, anti-CHIKV IgM and IgG). Bivariate analyses of clinical and biological features between groups were performed. Patients with CHIKV viremia presented typically with asymmetrical bilateral polyarthralgia (96.5%) affecting the lower (98%) and small joints (74.8%), as well as asthenia (88.6%), headache (70%), digestive trouble (63.3%), myalgia (59%), exanthems (47.8%), conjunctival hyperhemia (23%) and adenopathy (8.9%). Vertigo, cutaneous dysesthesia, pharyngitis and haemorrhages were seldom observed. So far unreported symptoms such as chondrocostal arthralgia (20%), entesopathies (1.6%), talalgia (14%) were also noted. Prurit was less frequent during the viremic than post-viremic phase (13.9% vs. 41.2%; p<0.001), whereas lymphopenia was more frequent (87.6% vs. 39.4%; p<0.001). Others biological abnormalities included leukopenia (38.3%), thrombocytopenia (37.3%), increased ASAT and ALAT blood levels (31.6 and 7.3%, respectively) and hypocalcemia (38.7%). Lymphopenia <1,000/mm(3) was very closely associated with viremic patients (Yule coefficient 0.82, positive predictive value 92.3%). Age under 65 was associated with a benign course, as no patients younger than 65 had to be hospitalized (Yule coefficient 0.78). CONCLUSIONS:The diagnosis of CHIKV infection in acute phase is based on commonly accepted clinical criteria (fever and arthralgia), however clinical and biological diffrences exist in acute phase depending on whether or not the patient is within the viremic phase of the infection

Prolonged Drying Trend Coincident with the Demise of Norse Settlement in Southern Greenland

Declining temperature has been thought to explain the abandonment of Norse settlements, southern Greenland, in the early 15th century, although limited paleoclimate evidence is available from the inner settlement region itself. Here, we reconstruct the temperature and hydroclimate history from lake sediments at a site adjacent to a former Norse farm. We find no substantial temperature changes during the settlement period but rather that the region experienced a persistent drying trend, which peaked in the 16th century. Drier climate would have notably reduced grass production, which was essential for livestock overwintering, and this drying trend is concurrent with a Norse diet shift. We conclude that increasingly dry conditions played a more important role in undermining the viability of the Eastern Settlement than minor temperature changes

Interaction of E2 Glycoprotein with Heparan Sulfate Is Crucial for Cellular Infection of Sindbis Virus

Cell culture-adapted strains of Sindbis virus (SINV) initially attach to cells by the ability to interact with heparan sulfate (HS) through selective mutation for positively charged amino acid (aa) scattered in E2 glycoprotein (W. B. Klimstra, K. D. Ryman, and R. E. Johnston, J. Virol. 72: 7357–7366, 1998). Here we have further confirmed that interaction of E2 protein with HS is crucial for cellular infection of SINV based on the reverse genetic system of XJ-160 virus, a Sindbis-like virus (SINLV). Both SINV YN87448 and SINLV XJ-160 displayed similar infectivity on BHK-21, Vero, or C6/36 cells, but XJ-160 failed to infect mouse embryonic fibroblast (MEF) cells. The molecular mechanisms underlying the selective infectivity of XJ-160 were approached by substituting the E1, E2, or both genes of XJ-160 with that of YN87448, and the chimeric virus was denominated as XJ-160/E1, XJ-160/E2, or XJ-160/E1E2, respectively. In contrast to the parental XJ-160, all chimeric viruses became infectious to wild-type MEF cells (MEF-wt). While MEF-Ext−/− cells, producing shortened HS chains, were resistant not only to XJ-160, but also to YN87448 as well as the chimeric viruses, indicating that the inability of XJ-160 to infect MEF-wt cells likely due to its incompetent discrimination of cellular HS. Treatment with heparin or HS-degrading enzyme resulted in a substantial decrease in plaque formation by YN87448, XJ-160/E2, and XJ-160/E1E2, but had marginal effect on XJ-160 and XJ-160/E1, suggesting that E2 glycoprotein from YN87448 plays a more important role than does E1 in mediating cellular HS-related cell infection. In addition, the peptide containing 145–150 aa from E2 gene of YN87448 specifically bound to heparin, while the corresponding peptide from the E2 gene of XJ-160 essentially showed no binding to heparin. As a new dataset, these results clearly confirm an essential role of E2 glycoprotein, especially the domain of 145–150 aa, in SINV cellular infection through the interaction with HS

The Sloan Digital Sky Survey Reverberation Mapping Project: No Evidence for Evolution in the M-sigma Relation to z~1

We present host stellar velocity dispersion measurements for a sample of 88 broad-line quasars at 0.10.6) from the Sloan Digital Sky Survey Reverberation Mapping (SDSS-RM) project. High signal-to-noise ratio coadded spectra (average S/N~30 per 69 km/s pixel) from SDSS-RM allowed decomposition of the host and quasar spectra, and measurement of the host stellar velocity dispersions and black hole (BH) masses using the single-epoch (SE) virial method. The large sample size and dynamic range in luminosity (L5100=10^(43.2-44.7) erg/s) lead to the first clear detection of a correlation between SE virial BH mass and host stellar velocity dispersion far beyond the local universe. However, the observed correlation is significantly flatter than the local relation, suggesting that there are selection biases in high-z luminosity-threshold quasar samples for such studies. Our uniform sample and analysis enable an investigation of the redshift evolution of the M-sigma relation free of caveats by comparing different samples/analyses at disjoint redshifts. We do not observe evolution of the M-sigma relation in our sample, up to z~1, but there is an indication that the relation flattens towards higher redshifts. Coupled with the increasing threshold luminosity with redshift in our sample, this again suggests certain selection biases are at work, and simple simulations demonstrate that a constant M-sigma relation is favored to z~1. Our results highlight the scientific potential of deep coadded spectroscopy from quasar monitoring programs, and offer a new path to probe the co-evolution of BHs and galaxies at earlier times.Comment: replaced with the accepted version (minor changes and updated references); ApJ in press; changed title to highlight the main resul