Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells

<p>Abstract</p> <p>Background</p> <p>The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell route.</p> <p>Results</p> <p>Here we analysed viral entry in wild type BeWo (CCR5⁺, CXCR4⁺) and BeWo-CD4⁺(CD4⁺, CCR5⁺, CXCR4⁺) cells. We report that HIV-1 internalisation is not restricted in either cell line. Levels of internalised p24 antigen between VSV-G HIV-1 pseudotypes and R5 or X4 virions were comparable. We next analysed the fate of internalised virions; X4 and R5 HIV-1 virions were less stable over time in BeWo cells than VSV-G HIV-1 pseudotypes. We then investigated the role of the proteasome in restricting cell-free HIV-1 infection in BeWo cells using proteasome inhibitors. We observed an increase in the levels of VSV-G pseudotyped HIV-1 infection in proteasome-inhibitor treated cells, but the infection by R5-Env or X4-Env pseudotyped virions remains restricted.</p> <p>Conclusion</p> <p>Collectively these results suggest that cell-free HIV-1 infection encounters a surface block leading to a non-productive entry route, which either actively targets incoming virions for non-proteasomal degradation, and impedes their release into the cytoplasm, or causes the inactivation of mechanisms essential for viral replication.</p

Chemical ozone loss in the Arctic winter 1991–1992

Chemical ozone loss in winter 1991–1992 is recalculated based on observations of the HALOE satellite instrument, Version 19, ER-2 aircraft measurements and balloon data. HALOE satellite observations are shown to be reliable in the lower stratosphere below 400 K, at altitudes where the measurements are most likely disturbed by the enhanced sulfate aerosol loading, as a result of the Mt.~Pinatubo eruption in June 1991. Significant chemical ozone loss (13–17 DU) is observed below 380 K from Kiruna balloon observations and HALOE satellite data between December 1991 and March 1992. For the two winters after the Mt. Pinatubo eruption, HALOE satellite observations show a stronger extent of chemical ozone loss towards lower altitudes compared to other Arctic winters between 1991 and 2003. In spite of already occurring deactivation of chlorine in March 1992, MIPAS-B and LPMA balloon observations indicate that chlorine was still activated at lower altitudes, consistent with observed chemical ozone loss occurring between February and March and April. Large chemical ozone loss of more than 70 DU in the Arctic winter 1991–1992 as calculated in earlier studies is corroborated here

Relation of BMI to a dual-energy X-ray absorptiometry measure of fatness

Dual-energy X-ray absorptiometry (DXA) is a valid technique for measuring the fat, bone and lean (muscle, organs and water) masses of the body. We evaluated relationships of BMI (kg/m2) with independent measurements of fat and lean masses using DXA in 226 adult volunteers. The evaluation was an application of a general approach to compositional data which has not previously been used for describing body composition. Using traditional regression analyses, when lean mass was held constant, BMI varied with fat mass (men r 0·75, P < 0·05 ; women r 0·85, P < 0·05); when fat mass was held constant, BMI varied with lean mass (men r 0·63, P < 0·05; women r 0·47, P < 0·05). In contrast, a regression model for compositional data revealed that BMI was: (a) strongly associated with log fat mass in both sexes (b1 4·86, P < 0·001 for all women and b1 5·96, P < 0·001 for all men); (b) not associated with bone mass, except in older men; (c) related to lean mass in women but not in men (b3 −4·04, P < 0·001 for all women and b1 −2·59, P < 0·15 for all men). Women with higher BMI tended to have more fat mass and more lean mass than women with lower BMI. Men with higher BMI had more fat mass but similar lean mass to men with lower BMI. Investigators need to be alert to the inaccuracy of BMI to assign a fatness risk factor to individuals, especially among wome

Influence of soil moisture on the movement of bromacil in soil

In previous research, bromacil gave good performance when it was applied in early fall with fairly dry soil conditions and before the fall germinating weeds had started growth. On the other hand, if bromacil was applied in late November, December, or January on nearly saturated soil with weeds that had grown for one or two months, weed control was quite noticeably reduced. Field and greenhouse studies were conducted at Corvallis, Oregon, to determine the influence of soil moisture and time of herbicide application on bromacil movement and performance. In one field trial, two or six acre-inches of water were applied by sprinkler irrigation at intervals following herbicide treatment. Intervals used were one day, two, four, or eight weeks following herbicide application on dry soil. Field bioassay with rape, wheat, oats, annual bluegrass, sugar beets, and winter field peas indicated that the performance of bromacil applied to dry soil was not affected by differences in irrigation levels or by the time interval between application and irrigation. Bioassay of core segments taken from the top six inches of soil showed no difference due to treatment and indicated that bromacil was not leached below three inches regardless of irrigation treatment. Of the bromacil found in the top three inches, approximately half of it was in the 0-1 inch segment. Difficulty in duplicating fall conditions appeared to have a definite effect on results of field studies. Extensive loss of soil moisture due to evaporation was probably the main factor causing deviation from the desired conditions. Another field trial included 0-, 1.5-, 3-, and 6-inch sprinkler irrigation rates on an annual bluegrass stand which had been treated with either pre- or post-emergence applications of bromacil. Irrigations were applied immediately after the post-emergence treatment. Both pre- and post-emergence applications of bromacil gave good control of annual bluegrass regardless of subsequent post-emergence irrigation. However, total precipitation during the first month was only 0.25 inches and where there was no irrigation, bromacil did not give adequate control. Greenhouse leaching studies with soil columns did not give satisfactory results. Consistent patterns of leaching throughout replications could not be accomplished. When bromacil movement was determined by the use of soil columns and subirrigation with 1.5 inches of water, there was no difference in movement whether it was applied to water-saturated or dry soil. A preliminary experiment with a shorter subirrigation period, however, resulted in less movement of the bromacil applied to dry soil. Bromacil movement in soil by subirrigation is not the same as leaching downward. Water moving through soil from subirrigation occurs through all except the very large pores; whereas in downward leaching, water primarily moves by gravity through the large pores once the small pores are filled

The Ionized Stellar Wind in Vela X-1 During Eclipse

We present a first analysis of a high resolution X-ray spectrum of the ionized stellar wind of Vela X-1 during eclipse. The data were obtained with the High Energy Transmission Grating Spectrometer onboard the Chandra X-ray Observatory. The spectrum is resolved into emission lines with fluxes between 0.02 and 1.04x10^4 ph/cm^2/s. We identify lines from a variety of charge states, including fluorescence lines from cold material, a warm photoionized wind. We can exclude signatures from collisionally ionized plasmas. For the first time we identify fluorescence lines from L-shell ions from lower Z elements. We also detect radiative recombination continua from a kT = 10 eV (1.2 x 10^5 K) photoionized optically thin gas. The fluorescence line fluxes infer the existence of optically thick and clumped matter within or outside the warm photoionized plasma.Comment: 4 pages, 2 figures, accepted by ApJ letter

Biological Markers of Auditory Gap Detection in Young, Middle-Aged, and Older Adults

The capability of processing rapid fluctuations in the temporal envelope of sound declines with age and this contributes to older adults' difficulties in understanding speech. Although, changes in central auditory processing during aging have been proposed as cause for communication deficits, an open question remains which stage of processing is mostly affected by age related changes. We investigated auditory temporal resolution in young, middle-aged, and older listeners with neuromagnetic evoked responses to gap stimuli with different leading marker and gap durations. Signal components specific for processing the physical details of sound stimuli as well as the auditory objects as a whole were derived from the evoked activity and served as biological markers for temporal processing at different cortical levels. Early oscillatory 40-Hz responses were elicited by the onsets of leading and lagging markers and indicated central registration of the gap with similar amplitude in all three age groups. High-gamma responses were predominantly related to the duration of no-gap stimuli or to the duration of gaps when present, and decreased in amplitude and phase locking with increasing age. Correspondingly, low-frequency activity around 200 ms and later was reduced in middle aged and older participants. High-gamma band, and long-latency low-frequency responses were interpreted as reflecting higher order processes related to the grouping of sound items into auditory objects and updating of memory for these objects. The observed effects indicate that age-related changes in auditory acuity have more to do with higher-order brain functions than previously thought