Nanosecond Pulsed Electric Field Modulates Electron Transport and Mitochondrial Structure and Function

Pulsed power treatment has been used to induce regulated cell death (RCD) in cells or ablate tumors in animals. A subset of pulsed power as electroporation with high voltage and pulse duration of milliseconds is used for biomedical treatment to induce pores in the plasma membrane of cells. Nanosecond Pulsed Electric Fields (nsPEFs)– an extension of electroporation, uses waveforms with pulse durations on the order of 10-900 nanoseconds. nsPEF treatment has demonstrated intracellular effects for potential biomedical applications. In this work, nsPEF treatment is used to demonstrate changes that affect viability, plasma membrane permeability ROS (Reactive Oxygen Species) in the cytosol and mitochondria, and Electron Transport Chain (ETC) in cell cultures. The preferential effectiveness of nsPEF on cultured cancerous versus non-cancerous breast epithelial cells is shown. The nsPEF treatment compromised the integrity of the plasma membrane and outer mitochondrial membrane (OMM), without affecting the integrity of the inner mitochondrial membrane (IMM). Also, nsPEF - changes in redox proteins such as NADH dehydrogenase both in the plasma membrane and in Complex I. A reduced cellular oxygen consumption after nsPEFs treatment indicates an alteration of the ETC at Complex I in intact and permeabilized cells as well as in isolated hepatocyte mitochondria This evidence suggests a new paradigm for considering nsPEF effects on cell function. The combination of nsPEF and rotenone synergistically enhanced ROS production in intact cells suggesting that nsPEF and rotenone act at different Complex I sites. These studies establish how nsPEF impacts several intracellular mechanisms that disrupt mitochondrial function directly on Complex I and IV and indirectly by Ca2+- and ROS-mediated mechanisms that cooperate to collapse the mitochondrial membrane potential and cause cell death. Together, these observations provide new evidence for mechanisms triggered by nsPEF treatment for inducing cancer cell death and changing cellular metabolism in ways useful for treating cancer and other diseases in clinical settings

COVID-19 and Biocybersecurity\u27s Increasing Role on Defending Forward

The evolving nature of warfare has been changing with cybersecurity and the use of advanced biotechnology in each aspect of the society is expanding and overlapping with the cyberworld. This intersection, which has been described as “biocybersecurity” (BCS), can become a major front of the 21st-century conflicts. There are three lines of BCS which make it a critical component of overall cybersecurity: (1) cyber operations within the area of BCS have life threatening consequences to a greater extent than other cyber operations, (2) the breach in health-related personal data is a significant tool for fatal attacks, and (3) health-related misinformation campaigns as a component of BCS can cause significant damage compared to other misinformation campaigns. Based on the observation that rather than initiating the necessary cooperation COVID-19 helped exacerbate the existing conflicts, the authors suggest that BCS needs to be considered as an essential component of the cyber doctrine, within the Defending Forward framework. The findings are expected to help future cyber policy developments

The production of OH in a nanosecond pulsed helium plasma jet impinging on water, saline, or pigskin

Applications of plasma-induced biological effects via reactive oxygen and nitrogen species (RONS) make the non-thermal atmospheric-pressure plasma jets an appealing tool in biomedical fields. The presence of biological materials, especially as part of the electrode circuit, may change the plasma properties and impact on the production of RONS at the plasma-biomaterial interface. Effects of biomaterials on the production of hydroxyl radicals (OH) in a nanosecond pulsed, atmospheric-pressure plasma jet were investigated using a needle-to-plate electrode configuration with water, phosphate-buffered saline (PBS), or pigskin covering the ground plate. Driven by 200 ns, 7 kV pulses at 1 kHz, a helium plasma jet was generated between the hollow needle electrode and the biomaterial. Temporally resolved UV-visible imaging showed that the use of pigskin slowed down the streamer head propagation, whereas a more pronounced surface ionization wave was developed on the surface when water was used. The highest OH(A-X) emission above the biomaterial surface was observed using the PBS-covered electrode plate comparing to water or pigskin. Spatiotemporally resolved laser-induced fluorescence (LIF) showed that more OH was produced in the region near the needle electrode for both water and PBS, and the use of pigskin resulted in least OH production overall. In addition, measurements of H2O2 production in the liquid were used to determine the OH concentration in the vicinity of the biomaterial and agreed well with the relative OH-LIF measurements obtained at the gas-liquid interface for water and PBS

Cyclophilin D Is a Sensor of Nano-Pulse Stimulation

Nano-Pulse Stimulation (NPS), a pulsed power-derived technology, stimulates structural and functional changes in plasma membranes and cellular organelles. NPS induces a Ca2+ influx and opening of the mitochondrial permeability transition pore (mPTP) that dissipates the mitochondrial membrane potential (ΔΨm) and, when sustained, induces regulated cell death. Here we show that in rat cardiomyoblasts (H9C2) cyclophilin D (CypD) is a mitochondrial sensor for NPS as defined by observations that loss of ΔΨm is Ca2+ and mitochondrial reactive oxygen species (mROS) dependent and cyclosporin A (CsA)-sensitive, which are diagnostic qualities for effects on CypD and the mPTP. Mechanistically, NPS stimulates increases in intracellular Ca2+ which enhances mROS in a dose dependent manner. The regulatory role of CypD on mPTP activation, is effectively inhibited at low Ca2+ concentrations and/or by CsA. Although NPS-induced dissipation of ΔΨm is largely Ca2+-dependent, the degree of Ca2+ sensitivities vary among cell types. Nevertheless, knockdown of the proapoptotic protein, APAF-1, and overexpression of the antiapoptotic protein, Bcl-xl, in human Jurkat T lymphocytes (E6.1) did not affect NPS-induced dissipation of ΔΨm or cell death. Taken together, these results indicate NPS induces activation of the mPTP through Ca2+-dependent, mROS-dependent, CsA-sensitive dissipation of the ΔΨm that is independent of caspase activation and insensitive to protection by Bcl-xl.https://digitalcommons.odu.edu/gradposters2021_gradschool/1001/thumbnail.jp

ICT Security Tools and Techniques Among Higher Education Institutions: A Critical Review

Higher education institutions (HEIs) are increasingly relying on digital technologies for classroom and organizational management, but this puts them at higher risk for information and communication (ICT security attacks. Recent studies show that HEIs have experienced more security breaches in ICT security composed of both cybersecurity an information security. A literature review was conducted to identify common ICT security practices in HEIs over the last decade. 11 journal articles were profiled and analyzed, revealing threats to HEIs’ security and protective measures in terms of organizational security, technological security, physical security, and standards and frameworks. Security tools and techniques were grouped into categories with specific ways to protect ICT security. HEIs also implement general security standards and guidelines, such as the ISO 27000-series and Center for Internet Security (CIS) controls, in their framework. Through synthesis and analysis of ICT security tools and techniques among HEIs, this critical review hopes to provide research directions on IT governance that academic and technical administrators can further explore to secure their information resources

Matters of Biocybersecurity with Consideration to Propaganda Outlets and Biological Agents

The modern era holds vast modalities in human data utilization. Within Biocybersecurity (BCS), categories of biological information, especially medical information transmitted online, can be viewed as pathways to destabilize organizations. Therefore, analysis of how the public, along with medical providers, process such data, and the methods by which false information, particularly propaganda, can be used to upset the flow of verified information to populations of medical professionals, is important for maintenance of public health. Herein, we discuss some interplay of BCS within the scope of propaganda and considerations for navigating the field