Infection with the human immunodeficiency virus (HIV) virus leads to clinical disease in humans but not in chimpanzees. Progression to disease is associated with activation of the immune system ...followed by loss of T helper cell function and a slow decline in CD4-positive lymphocytes. The presence of autoreactive and cytotoxic cells in humans but not chimpanzees suggests that mechanisms other than, or in addition to, direct virus-induced cell killing, are required for disease to develop. The observed changes are similar to those seen in chronic allogeneic disease. Here we show that a peptide from the carboxy terminus of gp120, predicted to have a structure similar to the major alpha-helices of major histocompatibility complex (MHC) class I and class II, acts as a cytolytic target when presented on syngeneic cells for alloactivated cytotoxic T effector cells. These data add further evidence to the hypothesis that HIV can act as an allostimulant due to its dual properties of CD4 binding and MHC mimicry. The ability to signal nonspecifically through the T cell receptor could explain the initially paradoxical responses of proliferation, anergy and apoptosis.
We present the GAMA Panchromatic Data Release (PDR) constituting over 230deg\(^2\) of imaging with photometry in 21 bands extending from the far-UV to the far-IR. These data complement our ...spectroscopic campaign of over 300k galaxies, and are compiled from observations with a variety of facilities including: GALEX, SDSS, VISTA, WISE, and Herschel, with the GAMA regions currently being surveyed by VST and scheduled for observations by ASKAP. These data are processed to a common astrometric solution, from which photometry is derived for 221,373 galaxies with r<19.8 mag. Online tools are provided to access and download data cutouts, or the full mosaics of the GAMA regions in each band. We focus, in particular, on the reduction and analysis of the VISTA VIKING data, and compare to earlier datasets (i.e., 2MASS and UKIDSS) before combining the data and examining its integrity. Having derived the 21-band photometric catalogue we proceed to fit the data using the energy balance code MAGPHYS. These measurements are then used to obtain the first fully empirical measurement of the 0.1-500\(\mu\)m energy output of the Universe. Exploring the Cosmic Spectral Energy Distribution (CSED) across three time-intervals (0.3-1.1Gyr, 1.1-1.8~Gyr and 1.8---2.4~Gyr), we find that the Universe is currently generating \((1.5 \pm 0.3) \times 10^{35}\) h\(_{70}\) W Mpc\(^{-3}\), down from \((2.5 \pm 0.2) \times 10^{35}\) h\(_{70}\) W Mpc\(^{-3}\) 2.3~Gyr ago. More importantly, we identify significant and smooth evolution in the integrated photon escape fraction at all wavelengths, with the UV escape fraction increasing from 27(18)% at z=0.18 in NUV(FUV) to 34(23)% at z=0.06. The GAMA PDR will allow for detailed studies of the energy production and outputs of individual systems, sub-populations, and representative galaxy samples at \(z<0.5\). The GAMA PDR can be found at: http://gama-psi.icrar.org/
Provider: - Institution: - Data provided by Europeana Collections- This policy brief is the result of an interdisciplinary research workshop with academics and practitioners, held at Bielefeld ...University in Germany on November 2014, in cooperation with COST Action IS1011 on Climate Change and Migration. The Bielefeld Consultation identified the need to raise awareness of the challenges of planned relocation as an adaptive strategy to climate change or as a consequence of climate policies. Acknowledging the risks and failures of planned relocation, the Consultation suggests principals and precautionary measures to ensure climate justice. And as a result of the Consultation, non-conclusive list of minimum standards for planned relocation are put forward for the consideration of policymakers and practitioners engaged in climate change adaptation and mitigation.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
The roles of protein kinase C and its substrates in development are poorly understood. Recently, we disrupted the mouse gene for a major cellular substrate for protein kinase C, the MARCKS protein ...(Proc. Natl. Acad. Sci. USA, 92, 944–948, 1995). The resulting phenotype consisted of universal perinatal lethality, agenesis of the corpus callosum and other forebrain commissures, and neuronal ectopia and other cortical and retinal lamination disturbances. These mice also had high frequencies of exencephaly (25% overall, 35% in females). In the present study, we have examined the normal expression of MARCKS and the various isozymes of protein kinase C at the time of cranial neural tube closure, in an attempt to correlate MARCKS expression in time and anatomical location with the exencephaly characteristic of MARCKS deficiency. Failure of neural tube closure occurred at various sites in the cranial neural tube, suggesting a cellular functional defect that was not limited to a specific location. Non-exencephalic MARCKS-deficient embryos appeared to be anatomically normal on embryonic day (E) 8.5–9.5. MARCKS and PKC α were expressed at the plasma membrane of the neuroepithelial cells comprising the future neural tube, as well as in the surface ectoderm and underlying mesenchyme. Endogenous protein kinase C species, comprising either or both α and δ, were capable of phosphorylating MARCKS in intact E8.5 embryos. Thus, MARCKS is expressed at the plasma membranes of the specific cell types involved in cranial neurulation; its deficiency presumably results in a still-to-be-elucidated functional defect in these cells that leads to exencephaly in a high proportion of cases.
A computer graphics molecular model of the C terminus of gp120 of HIV has been constructed using predicted secondary structure based on homologies with proteins for which X-ray crystallographic data ...have been published. The model shows sequences known to be important in CD4 binding in close proximity to regions with a high probability of forming alpha helical and beta strand motifs. The orientation adopted by these domains approximates to the known 3D structure of HLA-A2 alpha 2 chain without constraints based on HLA-A2 as a template being introduced. The model may therefore represent an energetically favourable conformation for a part of gp120 which mimics the binding domain for the T-cell receptor on MHC molecules. Recognition of gp120 as an alloepitope in high affinity association with CD4 would explain many of the sequelae of acquired immune deficiency on HIV infection.
A golden age for credit? Pfeuti, Elizabeth; Peters, Angus
Pensions expert,
09/2020
Magazine Article
The ability to move and transfer risk just stopped completely, accentuating the extreme nature of the market price vacuum," says Mr Peters. A gradual return in investor confidence saw companies ...return to debt issuance as part of a record-breaking fundraising effort. "Since the darkest days of March, there has been a steady recovery in the more liquid products that were hit the hardest or that do not have any real meaningful credit risk attached. Tegolin Harding, a director at Independent Trustee Services, points to the Term Asset-backed Securities Loan Facility, a Federal Reserve stimulus program, as one such example. Ms Harding stresses that schemes that have been able to pounce on discounted assets are typically those that have long ago tackled exposure to interest rate and inflation risks, and are well funded despite the March dip in both equity and bond markets.
