Release of Soluble Insulin Receptor From Neurons by Cerebrospinal Fluid From Patients With Neurocognitive Dysfunction and HIV Infection

Previously, we found that high levels of soluble insulin receptor (sIR) in the cerebrospinal fluid (CSF) of an HIV-infected women cohort were associated with the presence and severity of HIV-associated neurocognitive disorders (HAND). In this study we investigated if CSF from this population, HIV-1 Tat, and selected cytokines induces sIR secretion from human neuronal cells. Twenty-three (23) HIV-seropositive women stratified by cognitive status and five HIV- seronegative women were evaluated. Soluble IR levels were measured in the extracellular medium of neuronal cells (SH-SY5Y) that were exposed (for 24 h) to the CSF of patients. The levels of sIR, HIV-1 Tat, and cytokine levels (IL-2, IL4, IL-6, IFNγ, TNFα, and IL-10) were quantified in the CSF of participants by ELISA and flow cytometry. Neuronal secretion of sIR was measured after exposure (24 h) to HIV-1 Tat (0.5–250 nM), or specific cytokines. The effects of TNFα and HIV-1 Tat on sIR secretion were also evaluated in the presence of R7050 (TNFα antagonist; 10 nM). Neurons exposed to the CSF of HIV-infected women had higher sIR levels according to the severity of neurocognitive impairment of the participant. Increased CSF sIR levels were associated with the presence and severity of HAND and were positively correlated with CSF HIV-1 Tat levels in HIV-infected women with cognitive impairment. CSF levels of IL-2, IFNγ, and TNFα were significantly increased with HAND. However, only TNFα (5 pg/mL) and HIV-1 Tat (100 nM) induced a significant increase in neuronal sIR secretion after 24 h exposure, an effect that was antagonized when each were combined with R7050. Our data suggests that TNFα and HIV-1 Tat from the CSF of HIV-infected women may regulate the secretion of sIR from neuronal cells and that the effect of HIV-1 Tat on sIR secretion may depend on TNFα receptor activation

Report of the Topical Group on Physics Beyond the Standard Model at Energy Frontier for Snowmass 2021

This is the Snowmass2021 Energy Frontier (EF) Beyond the Standard Model (BSM) report. It combines the EF topical group reports of EF08 (Model-specific explorations), EF09 (More general explorations), and EF10 (Dark Matter at Colliders). The report includes a general introduction to BSM motivations and the comparative prospects for proposed future experiments for a broad range of potential BSM models and signatures, including compositeness, SUSY, leptoquarks, more general new bosons and fermions, long-lived particles, dark matter, charged-lepton flavor violation, and anomaly detection

Report of the Topical Group on Physics Beyond the Standard Model at Energy Frontier for Snowmass 2021

International audienceThis is the Snowmass2021 Energy Frontier (EF) Beyond the Standard Model (BSM) report. It combines the EF topical group reports of EF08 (Model-specific explorations), EF09 (More general explorations), and EF10 (Dark Matter at Colliders). The report includes a general introduction to BSM motivations and the comparative prospects for proposed future experiments for a broad range of potential BSM models and signatures, including compositeness, SUSY, leptoquarks, more general new bosons and fermions, long-lived particles, dark matter, charged-lepton flavor violation, and anomaly detection

Report of the Topical Group on Physics Beyond the Standard Model at Energy Frontier for Snowmass 2021

International audienceThis is the Snowmass2021 Energy Frontier (EF) Beyond the Standard Model (BSM) report. It combines the EF topical group reports of EF08 (Model-specific explorations), EF09 (More general explorations), and EF10 (Dark Matter at Colliders). The report includes a general introduction to BSM motivations and the comparative prospects for proposed future experiments for a broad range of potential BSM models and signatures, including compositeness, SUSY, leptoquarks, more general new bosons and fermions, long-lived particles, dark matter, charged-lepton flavor violation, and anomaly detection

Report of the topical group on physics beyond the standard model at energy frontier for snowmass 2021

This is the Snowmass2021 Energy Frontier (EF) Beyond the Standard Model (BSM) report. It combines the EF topical group reports of EF08 (Model-specific explorations), EF09 (More general explorations), and EF10 (Dark Matter at Colliders). The report includes a general introduction to BSM motivations and the comparative prospects for proposed future experiments for a broad range of potential BSM models and signatures, including compositeness, SUSY, leptoquarks, more general new bosons and fermions, long-lived particles, dark matter, charged-lepton flavor violation, and anomaly detection