In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.

Input: Consider Input: Context: Transport across the blood-brain barrier (BBB) is an important mediator of beta-amyloid (Aβ) accumulation in the brain and a contributing factor in the pathogenesis of Alzheimer's disease (AD). One of the receptors responsible for the transport of Aβ in the BBB is the low density lipoprotein receptor-related protein 1 (LRP1). LRP1 is susceptible to proteolytic shedding at the cell surface, which prevents endocytic transport of ligands. Previously, we reported a strong inverse correlation between LRP1 shedding in the brain and Aβ transit across the BBB. Several proteases contribute to the ectodomain shedding of LRP1 including the α-secretase, a desintegrin and metalloproteinase domain containing protein 10 (ADAM10).", 'The role of ADAM10 in the shedding of LRP1 and Aβ BBB clearance was assessed through pharmacological inhibition of ADAM10 in an in vitro model of the BBB and through the use of ADAM10 endothelial specific knock-out mice. In addition, an acute treatment paradigm with an ADAM10 inhibitor was also tested in an AD mouse model to assess the effect of ADAM10 inhibition on LRP1 shedding and Aβbrain accumulation.', 'In the current studies, inhibition of ADAM10 reduced LRP1 shedding in brain endothelial cultures and increased Aβ42 transit across an in vitro model of the BBB. Similarly, transgenic ADAM10 endothelial knockout mice displayed lower LRP1 shedding in the brain and significantly enhanced Aβ clearance across the BBB compared to wild-type animals. Acute treatment with the ADAM10-selective inhibitor GI254023X in an AD mouse model substantially reduced brain LRP1 shedding and increased Aβ40 levels in the plasma, indicating enhanced Aβ transit from the brain to the periphery. Furthermore, both soluble and insoluble Aβ40 and Aβ42 brain levels were decreased following GI254023X treatment, but these effects lacked statistical significance.\Question: Does inhibition of ADAM10 promote the clearance of Aβ across the BBB by reducing LRP1 ectodomain shedding?

Output: These studies demonstrate a role for ADAM10 in the ectodomain shedding of LRP1 in the brain and the clearance of Aβ across the BBB, which may provide a novel strategy for attenuating Aβ accumulation in the AD brain.


Input: Consider Input: Context: Thus far, live attenuated SIV has been the most successful method for vaccinating macaques against pathogenic SIV challenge; however, it is not clear what mechanisms are responsible for this protection. Adoptive transfer studies in mice have been integral to understanding live attenuated vaccine protection in models like Friend virus. Previous adoptive transfers in primates have failed as transferred cells are typically cleared within hours after transfer.', 'Here we describe adoptive transfer studies in Mauritian origin cynomolgus macaques (MCM), a non-human primate model with limited MHC diversity. Cells transferred between unrelated MHC-matched macaques persist for at least fourteen days but are rejected within 36 hours in MHC-mismatched macaques. Cells trafficked from the blood to peripheral lymphoid tissues within 12 hours of transfer.\Question: Do allogeneic lymphocytes persist and traffic in feral MHC-matched mauritian cynomolgus macaques?

Output: MHC-matched MCM provide the first viable primate model for adoptive transfer studies. Because macaques infected with SIV are the best model for HIV/AIDS pathogenesis, we can now directly study the correlates of protective immune responses to AIDS viruses. For example, plasma viral loads following pathogenic SIV challenge are reduced by several orders of magnitude in macaques previously immunized with attenuated SIV. Adoptive transfer of lymphocyte subpopulations from vaccinated donors into SIV-naïve animals may define the immune mechanisms responsible for protection and guide future vaccine development.


Input: Consider Input: Context: Although the significance of cell cycle checkpoints in overcoming low-dose hyper-radiosensitivity (HRS) has been proposed, the underlying mechanism of HRS in human hepatocellular cells remains unclear. Therefore, the aim of this study was to characterize HRS inhuman hepatocellular HepG2 cells and to explore the molecular mechanism(s) mediating this response.', 'HepG2 cells were exposed to various single doses of γ radiation (from 0\u2009Gy to 4\u2009Gy), and then were assayed at subsequent time-points. Survival curves were then generated using a linear-quadratic (LQ) equation and a modified induced repair model (MIRM). The percentage of cells in the G1, G2/M, and S phases of the cell cycle were also examined using propidium iodide (PI) staining and flow cytometry. Levels of total cell division cyclin 25C (Cdc25C) and phosphorylated Cdc25C were examined by Western blotting.', 'Low-dose γ radiation (<0.3\u2009Gy) induced HRS in HepG2 cells, while doses of 0.3, 0.5, and 2.0\u2009Gy γ radiation significantly arrested HepG2 cells in the G2/M phase. While total Cdc25C levels remained unchanged after irradiation, levels of phosphorylated Cdc25C markedly increased 6, 16, and 24\u2009h after treatment with 0.5 or 2.0\u2009Gy radiation, and they peaked after 16\u2009h. The latter observation is consistent with the G2/M arrest that was detected following irradiation.\Question: Is low-dose hyper-radiosensitivity in human hepatocellular HepG2 cells associated with Cdc25C-mediated G2/M cell cycle checkpoint control?


Output: These findings indicate that low-dose HRS in HepG2 cells may be associated with Cdc25C-mediated G2/M cell cycle checkpoint control.