Current models of autoimmunity suggest that delayed clearance of apoptotic cells leads to the presentation of apoptotic antigens in the context of inflammatory signals, with resultant autoimmunity. ...These models implicitly assume that, in contrast to early apoptotic cells (that retain membrane integrity), late apoptotic cells (with compromised membranes) act like necrotic cells (which also lack intact membranes), possibly because of the release of proinflammatory intracellular contents. We showed previously that early apoptotic and necrotic cells induce distinct mitogen-activated protein kinase modules in macrophages with which they interact. Exposure to apoptotic cells led to nearly complete inhibition of both basal and macrophage colony-stimulating factor-induced ERK1/2 by macrophages. In contrast, necrotic cells induced ERK1/2. We show here that apoptotic cells also strongly induced both c-Jun N-terminal kinase and p38, whereas necrotic cells had no detectable effect on c-Jun N-terminal kinase and p38. We also compared the signaling events induced in macrophages by exposure to early apoptotic cells, late apoptotic cells, and necrotic cells. The signaling events induced by late apoptotic cells were identical to and just as potent as those induced by early apoptotic cells. Thus, apoptotic cells are functionally equivalent throughout the cell death process, irrespective of membrane integrity. Moreover, the effects of both early and late apoptotic cells on signaling were dominant over those of necrotic cells. These data show that apoptotic cells do not become proinflammatory upon the loss of membrane integrity and are inconsistent with the notion that delayed clearance alone can lead to autoimmunity.
The gravitationally lensed star WHL0137-LS, nicknamed Earendel, was
identified with a photometric redshift $z_{phot} = 6.2 \pm 0.1$ based on images
taken with the Hubble Space Telescope. Here we ...present James Webb Space
Telescope (JWST) Near Infrared Camera (NIRCam) images of Earendel in 8 filters
spanning 0.8--5.0$\mu$m. In these higher resolution images, Earendel remains a
single unresolved point source on the lensing critical curve, increasing the
lower limit on the lensing magnification to $\mu > 4000$ and restricting the
source plane radius further to $r < 0.02$ pc, or $\sim 4000$ AU. These new
observations strengthen the conclusion that Earendel is best explained by an
individual star or multiple star system, and support the previous photometric
redshift estimate. Fitting grids of stellar spectra to our photometry yields a
stellar temperature of $T_{\mathrm{eff}} \simeq 13000$--16000 K assuming the
light is dominated by a single star. The delensed bolometric luminosity in this
case ranges from $\log(L) = 5.8$--6.6 $L_{\odot}$, which is in the range where
one expects luminous blue variable stars. Follow-up observations, including
JWST NIRSpec scheduled for late 2022, are needed to further unravel the nature
of this object, which presents a unique opportunity to study massive stars in
the first billion years of the universe.
Winter cover cropping on agricultural fields may improve rainfall infiltration and enhance soil water storage in areas such as California's Sacramento Valley, where the majority of precipitation ...occurs in the winter over a relatively short period of time in a series of heavy rainfall events. Enhanced soil water storage within the root zone on cover-cropped fields may benefit a grower by reducing the demand for surface water deliveries to meet the irrigation needs of subsequent crops. A study was conducted in the winters of 1998-1999 and 1999-2000 to determine a field's ability to conserve water for subsequent crops and to evaluate the effects of soil physical conditions on the water balance for three 4-year rotation farming systems within the Sustainable Agriculture Farming Systems (SAFS) Project at the University of California, Davis. Rainfall, runoff, and soil water content data was collected on two treatments using a winter cover crop and one treatment maintained fallow during the winter. Runoff and soil water content measurements were significantly affected by farming systems. Cumulative event runoff from 10.67 m 2 infiltration test areas was consistently higher on the fallow treatment than on the cover-cropped treatments. Winter 1999-2000 field water content measurements from 0-1.05 m depth were significantly higher in the cover-cropped systems than in the fallow treatment after field capacity had been reached. A hydrologic model was developed using the measured data and lysimeter data for evaporation and evapotranspiration to track daily water budget components (i.e., runoff, infiltration, evaporation, evapotranspiration, and soil water storage) and to assess changes in surface hydraulic conductivity. Model simulations showed that optimized hydraulic conductivity decreased for all treatments with successive runoff, but was less pronounced in cover-cropped plots. The study indicated that cover cropping can improve soil water storage for subsequent crops if the cover crop is destroyed before the additional soil water is lost as evapotranspiration.
The gravitationally lensed star WHL0137-LS, nicknamed Earendel, was identified with a photometric redshift \(z_{phot} = 6.2 \pm 0.1\) based on images taken with the Hubble Space Telescope. Here we ...present James Webb Space Telescope (JWST) Near Infrared Camera (NIRCam) images of Earendel in 8 filters spanning 0.8--5.0\(\mu\)m. In these higher resolution images, Earendel remains a single unresolved point source on the lensing critical curve, increasing the lower limit on the lensing magnification to \(\mu > 4000\) and restricting the source plane radius further to \(r < 0.02\) pc, or \(\sim 4000\) AU. These new observations strengthen the conclusion that Earendel is best explained by an individual star or multiple star system, and support the previous photometric redshift estimate. Fitting grids of stellar spectra to our photometry yields a stellar temperature of \(T_{\mathrm{eff}} \simeq 13000\)--16000 K assuming the light is dominated by a single star. The delensed bolometric luminosity in this case ranges from \(\log(L) = 5.8\)--6.6 \(L_{\odot}\), which is in the range where one expects luminous blue variable stars. Follow-up observations, including JWST NIRSpec scheduled for late 2022, are needed to further unravel the nature of this object, which presents a unique opportunity to study massive stars in the first billion years of the universe.
Traditional hybridoma and B cell cloning antibody discovery platforms have inherent limits in immune repertoire sampling depth. One consequence is that monoclonal antibody (mAb) leads often lack the ...necessary affinity for therapeutic applications, thus requiring labor-intensive and time-consuming affinity in vitro engineering optimization steps. Here, we show that high-affinity variants of mouse-derived mAbs can be rapidly obtained by testing of somatic sequence variants obtained by deep sequencing of antibody variable regions in immune repertories from immunized mice, even with a relatively sparse sampling of sequence variants from large sequence datasets. Affinity improvements can be achieved for mAbs with a wide range of affinities. The optimized antibody variants derived from immune repertoire mining have no detectable in vitro off-target binding and have in vivo clearance comparable to the parental mAbs, essential properties in therapeutic antibody leads. As generation of antibody variants in vitro is replaced by mining of variants generated in vivo, the procedure can be applied to rapidly identify affinity-optimized mAb variants.
Stored serum specimens from 723 patients with acute hepatitis B and 228 patients with chronic hepatitis B seen between 1977 and 1985 in the Hepatitis Clinic of the Los Angeles County-University of ...Southern California Medical Center, Los Angeles, CA, were tested for antibody to human immunodeficiency virus (anti-HIV). Risk factors were ordered hierarchically; cases with multiple risk factors were tabulated only in the risk group listed first on the clinic records. Anti-HIV was first detected in 1979, and by 1983 was found in about half of all homosexual men with chronic hepatitis B. The prevalence was significantly lower in patients with acute hepatitis B than in patients with chronic hepatitis B, and in nonhomosexual subjects compared with homosexual subjects. By 1985, 30 per cent of intravenous drug users with chronic hepatitis B were anti-HIV-positive. The highest annual seroconversion rate for anti-HIV, 21 per cent, was found in homosexual men in 1983. A significant association existed between anti-HIV positivity and hepatitis delta virus infection in homosexual men but not in drug abusers. This study provides data on the natural history of the human immunodeficiency virus epidemic in Los Angeles. Further study on the interaction of these different viruses is warranted.
This procedure describes the CDFA method for multipesticide residue analysis of fresh fruits and vegetables. An aliquot of chopped sample is blended with acetonitrile. The resulting aqueous ...acetonitrile extract is filtered and cleaned up via reverse phase solid phase extraction apparatus. The pH of the filtrate is adjusted to neutral using phosphate buffer and the acetonitrile layer is separated from the aqueous layer by a "salting out" process. An aliquot of the acetonitrile layer is concentrated with a K-D evaporator by forming an azeotrope with n-hexane. The prepared sample is assayed for pesticide residues using GLC and HPLC. The performance of this method was evaluated by fortifying 6 representative fruits and vegetables with 7 chlorinated hydrocarbons, 7 organophosphate and 7 N-methylcarbamate pesticides at 0.1-0.2 ppm. No matrix interference was observed and the recovery of residues varied among different samples as well as different pesticides. Chlorothalonil results varied widely with irreproducible recoveries. In general, the method appears to be fast, rugged, and able to detect routinely at the 0.01 ppm level
K+ transport in mitoplasts Chang, H S; Diwan, J J
Biochimica et biophysica acta,
08/1982, Letnik:
681, Številka:
2
Journal Article
Recenzirano
K+ transport into mitoplasts, prepared by digitonin disruption and removal of the outer membranes from rat liver mitochondria, has been studied. Unidirectional K+ influx has been measured by means of ...42K, in the presence of the respiratory substrate succinate. K+ influx is inhibited by CN-, antimycin A and dicyclohexylcarbodiimide, but is insensitive to oligomycin. A linear dependence of the reciprocal of the K+ -influx rate on the reciprocal of the external K+ concentration is observed. Under the conditions studied, the apparent Km for K+ of the transport mechanism is approx. 6 mM, while the Vmax of K+ influx is approx. 5 mu mol K+/g protein per min. The rate of K+ influx increases with increasing external pH over the range from 6.8 to 8.0. The observed kinetics, pH dependence and inhibitor sensitivity are essentially similar to previously reported characteristics of K+ transport into intact rat liver mitochondria. It is concluded that the outer mitochondrial membrane does not not have a role in controlling K+ flux into rat liver mitochondria.
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