Considerations for Conducting Bring Your Own "Device" (BYOD) Clinical Studies.

Background: Digital health technologies are attracting attention as novel tools for data collection in clinical research. They present alternative methods compared to in-clinic data collection, which often yields snapshots of the participants' physiology, behavior, and function that may be prone to biases and artifacts, e.g.

Nuclear Factor κB and Adenosine Receptors: Biochemical and Behavioral Profiling.

Adenosine is produced primarily by the metabolism of ATP and mediates its physiological actions by interacting primarily with adenosine receptors (ARs) on the plasma membranes of different cell types in the body. Activation of these G protein-coupled receptors promotes activation of diverse cellular signaling pathways that define their tissue-specific functions. One of the major actions of adenosine is cytoprotection, mediated primarily via two ARs - A(1) (A(1)AR) and A(3) (A(3)AR).

Matrix-specific protein kinase A signaling regulates p21-activated kinase activation by flow in endothelial cells.

Rationale: Atherosclerosis is initiated by blood flow patterns that activate inflammatory pathways in endothelial cells. Activation of inflammatory signaling by fluid shear stress is highly dependent on the composition of the subendothelial extracellular matrix. The basement membrane proteins laminin and collagen found in normal vessels suppress flow-induced p21 activated kinase (PAK) and nuclear factor (NF)-kappaB activation.

Focal adhesion kinase modulates activation of NF-kappaB by flow in endothelial cells.

Atherogenesis involves activation of NF-kappaB in endothelial cells by fluid shear stress. Because this pathway involves integrins, we investigated the involvement of focal adhesion kinase (FAK). We found that FAK was not required for flow-stimulated translocation of the p65 NF-kappaB subunit to the nucleus but was essential for phosphorylation of p65 on serine 536 and induction of ICAM-1, an NF-kappaB-dependent gene.

The subendothelial extracellular matrix modulates JNK activation by flow.

Atherosclerosis begins as local inflammation of artery walls at sites of disturbed flow. JNK (c-Jun NH(2)-terminal kinase) is thought to be among the major regulators of flow-dependent inflammatory gene expression in endothelial cells in atherosclerosis. We now show that JNK activation by both onset of laminar flow and long-term oscillatory flow is matrix-specific, with enhanced activation on fibronectin compared to basement membrane protein or collagen.

Expression of striatal adenosine and dopamine receptors in mice deficient in the p50 subunit of NF-kappaB.

The striatal dopamine D2 receptor (D2R) and adenosine A2A receptor (A2AAR) exhibit mutually antagonistic effects through physical interactions and by differential modulation of post-receptor signaling pathways. The expression of the A2AAR and the D2R is differentially regulated by nuclear factor-kappaB (NF-kappaB). In this report, we determined the role of NF-kappaB in regulation of these receptors by comparing mice deficient in the NF-kappaB p50 subunit (p50 KO) with genetically intact B6129PF2/J (F2) mice.

Activation of the adenosine A1 receptor inhibits HIV-1 tat-induced apoptosis by reducing nuclear factor-kappaB activation and inducible nitric-oxide synthase.

Human immunodeficiency virus dementia (HIV-D) is a nonfocal central nervous system manifestation characterized by cognitive, behavioral, and motor abnormalities. The pathophysiology of neuronal damage in HIV-D includes a direct toxic effect of viral proteins on neuronal cells and an indirect effect caused by the release of inflammatory mediators and neurotoxins by activated macrophages/microglia and astrocytes, culminating into neuronal apoptosis. Previous studies have documented that the nucleoside adenosine mediates neuroprotection by activating adenosine A(1) receptor subtype (A(1)AR) linked to suppression of neuronal excitability.

Nitric oxide serves as an endogenous regulator of neuronal adenosine A1 receptor expression.

Nitric oxide (NO) radicals are produced during normal cellular function, after tissue injury, and in response to immune system activation during infection. The transformation of NO to peroxynitrite is essential for mediating some of its physiological and/or cytotoxic actions. As the expression of the adenosine A1 receptor (A1AR) is regulated by oxidative stress, we evaluated the role of NO in the regulation of A1AR expression, a G protein-coupled receptor involved in cytoprotection in the central nervous system.

Sleep mechanisms in health and disease.

Excess sleepiness, abnormal sleep patterns, non-restorative sleep, and fatigue are becoming increasingly pervasive in modern society. Identifying substances and mechanisms that modulate sleep and vigilance during health and disease is a critical prelude to eventual development of interventions to prevent or alleviate these disabling problems. A unified interdisciplinary approach that includes neurophysiology, neuroanatomy, neurochemistry, and molecular biology will promote elucidation of the complex biology of sleep.