Transcriptional response of primary hippocampal neurons following exposure to 3.0 GHz radiofrequency electromagnetic fields.

Exposure to radiofrequency (RF) electromagnetic fields (EMF) has been associated with the modulation of neuronal electrophysiology and synaptic plasticity. Given the potential of these changes to coincide with alterations in gene expression, this study investigated whether a transcriptional response would occur in neurons following exposure to RF-EMF, under both thermal and nonthermal conditions. Rat primary hippocampal neurons (PHNs) underwent either a single (one-time) or a multiple (3-times, once a day) exposures to RF-EMF (3.

Filament displacement image analytics tool for use in investigating dynamics of dense microtubule networks.

The fate and motion of cells is influenced by a variety of physical characteristics of their microenvironments. Traditionally, mechanobiology focuses on external mechanical phenomena such as cell movement and environmental sensing. However, cells are inherently dynamic, where internal waves and internal oscillations are a hallmark of living cells observed under a microscope.

Effect of nanosecond pulsed electric fields (nsPEFs) on coronavirus survival.

Previous work demonstrated inactivation of influenza virus by GHz frequency electromagnetic fields. Despite theoretical and experimental results, the underlying mechanism driving this inactivation remains unknown. One hypothesis is that the electromagnetic field is causing damage to the virion membrane (and therefore changing spike protein orientation) rendering the virus unable to attach and infect host cells.

Evaluation of inactivation of bovine coronavirus by low-level radiofrequency irradiation.

Inactivation of influenza A virus by radiofrequency (RF) energy exposure at levels near Institute of Electrical and Electronics Engineers (IEEE) safety thresholds has been reported. The authors hypothesized that this inactivation was through a structure-resonant energy transfer mechanism. If this hypothesis is confirmed, such a technology could be used to prevent transmission of virus in occupied public spaces where RF irradiation of surfaces could be performed at scale.

Analysis of global DNA methylation changes in human keratinocytes immediately following exposure to a 900 MHz radiofrequency field.

The increasing use of nonionizing radiofrequency electromagnetic fields (RF-EMFs) in a wide range of technologies necessitates studies to further understanding of biological effects from exposures to such forms of electromagnetic fields. While previous studies have described mechanisms for cellular changes occurring following exposure to low-intensity RF-EMFs, the role of molecular epigenetics has not been thoroughly investigated. Specifically unresolved is the effect of RF-EMFs on deoxyribonucleic acid (DNA) methylation, which is a powerful epigenetic process, used by cells to regulate gene expression.

Evaluation of Viral Inactivation on Dry Surface by High Peak Power Microwave (HPPM) Exposure.

Previous research has shown that virus infectivity can be dramatically reduced by radio frequency exposure in the gigahertz (GHz) frequency range. Given the worldwide SARS-CoV-2 pandemic, which has caused over 1 million deaths and has had a profound global economic impact, there is a need for a noninvasive technology that can reduce the transmission of virus among humans. RF is a potential wide area-of-effect viral decontamination technology that could be used in hospital rooms where patients are expelling virus, in grocery and convenience stores where local populations mix, and in first responder settings where rapid medical response spans many potentially infected locations within hours.

Changes in the excitability of primary hippocampal neurons following exposure to 3.0 GHz radiofrequency electromagnetic fields.

Exposures to radiofrequency electromagnetic fields (RF-EMFs, 100 kHz to 6 GHz) have been associated with both positive and negative effects on cognitive behavior. To elucidate the mechanism of RF-EMF interaction, a few studies have examined its impact on neuronal activity and synaptic plasticity. However, there is still a need for additional basic research that further our understanding of the underlying mechanisms of RF-EMFs on the neuronal system.

Terahertz spectroscopy of human skin tissue models with different melanin content.

Terahertz imaging has been proposed for burns and skin cancer identification. However, the role of melanocytes, melanosomes, melanin content and distribution in determining the terahertz optical properties of human skin has not been investigated. We use terahertz time domain spectroscopy to measure the optical properties of pigmented human skin tissue models from Asian, Black, and Caucasian donors.

Adult human dermal fibroblasts exposed to nanosecond electrical pulses exhibit genetic biomarkers of mechanical stress.

Background: Exposure of cells to very short (<1 µs) electric pulses in the megavolt/meter range have been shown to cause a multitude of effects, both physical and molecular in nature. Physically, nanosecond electrical pulses (nsEP) can cause disruption of the plasma membrane, cellular swelling, shrinking and blebbing. Molecularly, nsEP have been shown to activate signaling pathways, produce oxidative stress, stimulate hormone secretion and induce both apoptotic and necrotic death.

Qualitative Behavior of the Low-Frequency Vibrational Dynamics of Microtubules and the Surrounding Water.

The dynamics of the low-frequency vibrational modes of microtubules play a key role in many theoretical models regarding their biological function. We analyze these dynamics through large scale, classical molecular dynamics simulations of a microtubule composed of 42 tubulin heterodimers to provide insights into the qualitative nature of the vibrational energy absorption and dissipation mechanisms. The computed microtubule absorption spectra and vibrational density of states in the terahertz regime are presented, along with an analysis of the vibrational dephasing rates of the tubulin monomer center of mass dynamics, which are shown to be overdamped.

Evaluation of the Genetic Response of U937 and Jurkat Cells to 10-Nanosecond Electrical Pulses (nsEP).

Nanosecond electrical pulse (nsEP) exposure activates signaling pathways, produces oxidative stress, stimulates hormone secretion, causes cell swelling and induces apoptotic and necrotic death. The underlying biophysical connection(s) between these diverse cellular reactions and nsEP has yet to be elucidated. Using global genetic analysis, we evaluated how two commonly studied cell types, U937 and Jurkat, respond to nsEP exposure.

Using a portable terahertz spectrometer to measure the optical properties of in vivo human skin.

Terahertz (THz) time-domain spectroscopy systems permit the measurement of a tissue's hydration level. This feature makes THz spectrometers excellent tools for the noninvasive assessment of skin; however, current systems are large, heavy and not ideal for clinical settings. We previously demonstrated that a portable, compact THz spectrometer permitted measurement of porcine skin optical properties that were comparable to those collected with conventional systems.

Temporal gene expression kinetics for human keratinocytes exposed to hyperthermic stress.

The gene expression kinetics for human cells exposed to hyperthermic stress are not well characterized. In this study, we identified and characterized the genes that are differentially expressed in human epidermal keratinocyte (HEK) cells exposed to hyperthermic stress. In order to obtain temporal gene expression kinetics, we exposed HEK cells to a heat stress protocol (44 °C for 40 min) and used messenger RNA (mRNA) microarrays at 0 h, 4 h and 24 h post-exposure.

Oncolytic targeting of androgen-sensitive prostate tumor by the respiratory syncytial virus (RSV): consequences of deficient interferon-dependent antiviral defense.

Background: Oncolytic virotherapy for cancer treatment utilizes viruses for selective infection and death of cancer cells without any adverse effect on normal cells. We previously reported that the human respiratory syncytial virus (RSV) is a novel oncolytic virus against androgen-independent PC-3 human prostate cancer cells. The present study extends the result to androgen-dependent prostate cancer, and explores the underlying mechanism that triggers RSV-induced oncolysis of prostate cancer cells.

Functionality of unliganded VDR in breast cancer cells: repressive action on CYP24 basal transcription.

It is well-established that CYP24, an immediate target gene of VDR is upregulated by VDR ligands. This study is focused on the functional role of unliganded VDR by investigating the correlation between the expression of VDR protein and basal mRNA levels of CYP24 in breast cancer cell lines. Analyses of multiple breast cancer cell lines demonstrated an inverse correlation between VDR protein expression and CYP24 mRNA expression levels; while in the presence of ligand, VDR protein level was positively correlated with CYP24 expression.

Loss of androgen receptor in aging and oxidative stress through Myb protooncoprotein-regulated reciprocal chromatin dynamics of p53 and poly(ADP-ribose) polymerase PARP-1.

Poly(ADP-ribosyl)ation of transcription factors and coregulators, mediated by the poly(ADP-ribose) polymerase PARP-1, has been emerging as an important epigenetic mechanism that controls transcriptional dynamics in response to diverse intra- and extracellular signals. PARP-1 activity is also implicated in the regulation of mammalian lifespan. Herein we show that transcriptional down-regulation of androgen receptor (AR) in the aging rat liver and in oxidatively stressed hepatoma cells involves exchange of a PARP-1-associated, p/CAF-containing coactivator assembly for a p53-interacting, Groucho/TLE1-, and mSin3A-included corepressor complex at an age- and oxidant-responsive DNA element (age-dependent factor (ADF) element) in the AR promoter.

The xenobiotic-sensing nuclear receptors pregnane X receptor, constitutive androstane receptor, and orphan nuclear receptor hepatocyte nuclear factor 4alpha in the regulation of human steroid-/bile acid-sulfotransferase.

The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are the primary transcription factors coordinating induced expression of the enzymes and proteins directing oxidative, conjugative, and transport phases of endobiotic and xenobiotic metabolism, whereas hepatocyte nuclear factor 4alpha (HNF4alpha), a regulator of hepatic lipid homeostasis, can modify the PXR/CAR response. Steroid- and bile acid-sulfotransferase (SULT2A1) promotes phase II metabolism through its sulfonating action on certain endobiotics, including steroids and bile acids, and on diverse xenobiotics, including therapeutic drugs. This study describes characterization of a PXR- and CAR-inducible composite element in the human SULT2A1 promoter and its synergistic interaction with HNF4alpha.

Xenobiotic- and vitamin D-responsive induction of the steroid/bile acid-sulfotransferase Sult2A1 in young and old mice: the role of a gene enhancer in the liver chromatin.

The xenobiotic-activated nuclear receptors PXR (pregnane X receptor) and CAR (constitutive androstane receptor) and the vitamin D(3)-activated nuclear receptor VDR regulate steroid and xenobiotic metabolism by inducing the phase I cytochrome P450 monooxygenases, phase II conjugating transferases, and the phase III transporters, which mediate the efflux of water-soluble lipid metabolites from cells. Metabolic stress due to the deviant expression of steroid- and xenobiotic-metabolizing enzymes is known to have severe health consequences including accelerated aging, and increased expression of these enzymes is associated with extended longevity [Gachon, F, Olela, FF, Schaad, O, Descombes, P and Schibler, U, 2006. The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification.

Vitamin D receptor regulation of the steroid/bile acid sulfotransferase SULT2A1.

SULT2A1 is a sulfo-conjugating phase II enzyme expressed at very high levels in the liver and intestine, the two major first-pass metabolic tissues, and in the steroidogenic adrenal tissue. SULT2A1 acts preferentially on the hydroxysteroids dehydroepiandrosterone, testosterone/dihydrotestosterone, and pregnenolone and on cholesterol-derived amphipathic sterol bile acids. Several therapeutic drugs and other xenobiotics, which include xenoestrogens, are also sulfonated by this cytosolic steroid/bile acid sulfotransferase.

An essential role of the CAAT/enhancer binding protein-alpha in the vitamin D-induced expression of the human steroid/bile acid-sulfotransferase (SULT2A1).

The vitamin D receptor (VDR) regulates steroid and drug metabolism by inducing the genes encoding phase I and phase II enzymes. SULT2A1 is a liver- and intestine-expressed sulfo-conjugating enzyme that converts the alcohol-OH of neutral steroids, bile acids, and drugs to water-soluble sulfated metabolites. 1alpha,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] induces SULT2A1 gene transcription after the recruitment of VDR to the vitamin D-responsive chromatin region of SULT2A1.

Gene regulation for the senescence marker protein DHEA-sulfotransferase by the xenobiotic-activated nuclear pregnane X receptor (PXR).

Dehydroepiandrosterone (DHEA)-sulfotransferase (SULT2A1) is a phase II metabolizing/detoxifying enzyme with substrate preference for physiological hydroxysteroids, diverse drugs and other xenobiotics. The first-pass tissues (liver and intestine) express SULT2A1 at high levels. In senescent male rodents, Sult2A1 gene transcription in the liver is markedly enhanced and calorie restriction retards this increase.

Dehydroepiandrosterone sulfotransferase is a target for transcriptional induction by the vitamin D receptor.

Dehydroepiandrosterone sulfotransferase (SULT2A1) is a cytosolic enzyme that mediates sulfo-conjugation of endogenous hydroxysteroids (dehydroepiandrosterone, testosterone, bile acids), and diverse xenobiotic compounds. Upon sulfonation, SULT2A1 substrates become polar and water-soluble and thus suitable for rapid excretion. SULT2A1 is abundantly expressed in the liver and intestine.