Identification and simian immunodeficiency virus infection of CD1d-restricted macaque natural killer T cells

Natural killer T (NKT) cells express a highly conserved T-cell receptor (TCR) and recognize glycolipids in the context of CD1d molecules. We recently demonstrated that CD4+ NKT cells are highly susceptible to human immunodeficiency virus type 1 (HIV-1) infection and are selectively depleted in HIV-infected individuals. Here, we identified macaque NKT cells using CD1d tetramers and human Valpha24 antibodies. Similar to human NKT cells, alpha-galactosylceramide (alpha-GalCer)-pulsed dendritic cells activate and expand macaque NKT cells. Upon restimulation with alpha-GalCer-pulsed CD1d(+) cells, macaque NKT cells secreted high levels of cytokines, a characteristic of these T cells. Remarkably, the majority of resting and activated macaque NKT cells expressed CD8, and a smaller portion expressed CD4. Macaque NKT cells also expressed the HIV-1/simian immunodeficiency virus (SIV) coreceptor CCR5, and the CD4+ subset was susceptible to SIV infection. Identification of macaque NKT cells has major implications for delineating the role of these cells in nonhuman primate disease models of HIV as well as other pathological conditions, such as allograft rejection and autoimmunity.     

Nef-mediated downregulation of CD4 enhances human immunodeficiency virus type 1 replication in primary T lymphocytes

The accessory protein Nef plays a crucial role in primate lentivirus pathogenesis. Nef enhances human immunodeficiency virus type 1 (HIV-1) infectivity in culture and stimulates viral replication in primary T cells. In this study, we investigated the relationship between HIV-1 replication efficiency in CD4(+) T cells purified from human blood and two various known activities of Nef, CD4 downregulation and single-cycle infectivity enhancement. Using a battery of reporter viruses containing point mutations in nef, we observed a strong genetic correlation between CD4 downregulation by Nef during acute HIV-1 infection of activated T cells and HIV-1 replication efficiency in T cells. In contrast, HIV-1 replication ability was not significantly correlated with the ability of Nef to enhance single-cycle virion infectivity, as determined by using viruses produced in cells lacking CD4. These results demonstrate that CD4 downregulation by Nef plays a crucial role in HIV-1 replication in activated T cells and underscore the potential for the development of therapies targeting this conserved activity of Nef.     

Elimination of HIV-1-Infected Primary T Cell Reservoirs in an In Vitro Model of Latency

Establishment of long-lived cellular reservoirs of HIV-1 represents a major therapeutic challenge to virus eradication. In this study, we utilized a human primary cell model of HIV-1 latency to evaluate the requirements for efficient virus reactivation from, and the selective elimination of, latently infected human T cells. Ectopic expression of BCL2 supported the replication and spread of R5-tropic HIV-1 in activated CD4⁺ T cells. After IL-2 withdrawal, the HIV-1-infected T cells survived as resting cells for several months. Unexpectedly, these resting T cells continue to produce detectable levels of infectious virus, albeit at a lower frequency than cells maintained in IL-2. In the presence of HIV-1 inhibitors, reactivation of the resting T cells with γc-cytokines and allogeneic dendritic cells completely extinguished HIV-1 infectivity. We also evaluated the ability of the bacterial LukED cytotoxin to target and kill CCR5-expressing cells. After γc-cytokine stimulation, LukED treatment eliminated both HIV-1-infected resting cells and the non-infected CCR5⁺ cells. Importantly, complete clearance of in vitro HIV-1 reservoirs by LukED required a lower threshold of cytokine signals relative to HIV-1 inhibitors. Thus, the primary T cell-based HIV-1 latency model could facilitate the development of novel agents and therapeutic strategies that could effectively eradicate HIV-1.     

3-Pyridinylboronic Acid Ameliorates Rotenone-Induced Oxidative Stress Through Nrf2 Target Genes in Zebrafish Embryos

Neurochemical Research - Parkinson’s disease (PD) is one of the most common forms of neurodegenerative diseases and research on potential therapeutic agents for PD continues. Rotenone is a...     

Influence of membrane fouling reducers (MFRs) on filterability of disperse mixed liquor of jet loop bioreactors

The effects of membrane fouling reducers (MFRs) (the cationic polyelectrolyte (CPE) and FeCI₃) on membrane fouling were studied in a lab-scale jet loop submerged membrane bioreactor (JL-SMBR) system. The optimum dosages of MFRs (CPE dosage = 20 mg g⁻¹MLSS, FeCI₃ dosage = 14 mg g⁻¹MLSS) were continuously fed to JL-SMBR system. The soluble and bound EPS concentrations as well as MLSS concentration in the mixed liquor of JL-SMBR were not changed substantially by the addition of MFRs. However, significant differences were observed in particle size and relative hydrophobicity. Filtration tests were performed by using different membrane types (polycarbonate (PC) and nitrocellulose mixed ester (ME)) and various pore sizes (0.45-0.22-0.1 μm). The steady state fluxes (J_ss) of membranes increased at all membranes after MFRs addition to JL-SMBR. The filtration results showed that MFRs addition was an effective approach in terms of improvement in filtration performance for both membrane types.     

Alien marine fishes deplete algal biomass in the Eastern Mediterranean

One of the most degraded states of the Mediterranean rocky infralittoral ecosystem is a barren composed solely of bare rock and patches of crustose coralline algae. Barrens are typically created by the grazing action of large sea urchin populations. In 2008 we observed extensive areas almost devoid of erect algae, where sea urchins were rare, on the Mediterranean coast of Turkey. To determine the origin of those urchin-less 'barrens', we conducted a fish exclusion experiment. We found that, in the absence of fish grazing, a well-developed algal assemblage grew within three months. Underwater fish censuses and observations suggest that two alien herbivorous fish from the Red Sea (Siganus luridus and S. rivulatus) are responsible for the creation and maintenance of these benthic communities with extremely low biomass. The shift from well-developed native algal assemblages to 'barrens' implies a dramatic decline in biogenic habitat complexity, biodiversity and biomass. A targeted Siganus fishery could help restore the macroalgal beds of the rocky infralittoral on the Turkish coast.