3,833 research outputs found
HIVā1, Drug Addiction, and Autophagy
Despite the dramatic success of combined antiretroviral therapies (cART) in controlling peripheral virus replication, the prevalence of HIVā1āassociated neurocognitive disorders (HAND) is on a rise as infected individuals continue to live longer. Almost half of the infected individuals on ART develop HAND, out of which at least 30% suffer from a comorbid condition of substance abuse. Involvement of autophagy has been implicated not only in HIVā1 infection of the CNS but also in CNS cells exposed to drugs such as amphetamine, opiates, and cocaine, contributing in turn, to cellular dysfunction. HIVā1 is known to interfere with the autophagy pathway, resulting in turn to upregulation of HIVā1 replication. Specifically, different HIVā1 proteins such as TAT, gp120, and Nef have been shown to act on various stages of autophagy such as initiation and maturation and to affect overall autophagy levels. Whether or not abused drugs and HIVā1 can cooperate to dysregulate autophagy, however, remains unclear. This chapter is focused on identifying the molecular mechanism(s) underlying HIVā1 (proteins) and cocaine, opiate, methamphetamineāmediated impairment of autophagy. Such effects could underlie the synergistic effects of HIVā1 and abused drugs in exacerbating symptoms of HAND
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A Targeted Quantitative Proteomic Method Revealed a Substantial Reprogramming of Kinome during Melanoma Metastasis.
Kinases are involved in numerous critical cell signaling processes, and dysregulation in kinase signaling is implicated in many types of human cancers. In this study, we applied a parallel-reaction monitoring (PRM)-based targeted proteomic method to assess kinome reprogramming during melanoma metastasis in three pairs of matched primary/metastatic human melanoma cell lines. Around 300 kinases were detected in each pair of cell lines, and the results showed that Janus kinase 3 (JAK3) was with reduced expression in the metastatic lines of all three pairs of melanoma cells. Interrogation of The Cancer Genome Atlas (TCGA) data showed that reduced expression of JAK3 is correlated with poorer prognosis in melanoma patients. Additionally, metastatic human melanoma cells/tissues exhibited diminished levels of JAK3 mRNA relative to primary melanoma cells/tissues. Moreover, JAK3 suppresses the migration and invasion of cultured melanoma cells by modulating the activities of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). In summary, our targeted kinome profiling method provided by far the most comprehensive dataset for kinome reprogramming associated with melanoma progression, which builds a solid foundation for examining the functions of other kinases in melanoma metastasis. Moreover, our results reveal a role of JAK3 as a potential suppressor for melanoma metastasis
High visibility on-chip quantum interference of single surface plasmons
Quantum photonic integrated circuits (QPICs) based on dielectric waveguides
have been widely used in linear optical quantum computation. Recently, surface
plasmons have been introduced to this application because they can confine and
manipulate light beyond the diffraction limit. In this study, the on-chip
quantum interference of two single surface plasmons was achieved using
dielectric-loaded surface-plasmon-polariton waveguides. The high visibility
(greater than 90%) proves the bosonic nature of single plasmons and emphasizes
the feasibility of achieving basic quantum logic gates for linear optical
quantum computation. The effect of intrinsic losses in plasmonic waveguides
with regard to quantum information processing is also discussed. Although the
influence of this effect was negligible in the current experiment, our studies
reveal that such losses can dramatically reduce quantum interference visibility
in certain cases; thus, quantum coherence must be carefully considered when
designing QPIC devices.Comment: 6 pages, 4 figure
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