ABSTRACT Cardiovascular disease, especially heart failure (HF) is the leading cause of death in patients with diabetes. Individuals with diabetes are prone to a special type of cardiomyopathy called diabetic cardiomyopathy (DCM), which cannot be explained by heart diseases such as hypertension or coronary artery disease, and can contribute to HF. Unfortunately, the current treatment strategy for diabetes-related cardiovascular complications is mainly to control blood glucose levels; nonetheless, the improvement of cardiac structure and function is not ideal. The transient receptor potential cation channel subfamily V member 1 (TRPV1), a nonselective cation channel, has been shown to be universally expressed in the cardiovascular system. Increasing evidence has shown that the activation of TRPV1 channel has a potential protective influence on the cardiovascular system. Numerous studies show that activating TRPV1 channels can improve the occurrence and progression of diabetes-related complications, including cardiomyopathy; however, the specific mechanisms and effects are unclear. In this review, we summarize that TRPV1 channel activation plays a protective role in the heart of diabetic models from oxidation/nitrification stress, mitochondrial function, endothelial function, inflammation, and cardiac energy metabolism to inhibit the occurrence and progression of DCM. Therefore, TRPV1 may become a latent target for the prevention and treatment of diabetes-induced cardiovascular complications.

ABSTRACT Sex hormones and the reproductive cycle (estrus in rodents and menstrual in humans) have a known impact on arterial function. In spite of this, sex hormones and the estrus/menstrual cycle are often neglected experimental factors in vascular basic preclinical scientific research. Recent research by our own laboratory indicates that cyclical changes in serum concentrations of sex -hormones across the rat estrus cycle, primarily estradiol, have significant consequences for the subcellular trafficking and function of KV7. Vascular potassium channels, including KV7, are essential components of vascular reactivity. Our study represents a small part of a growing field of literature aimed at determining the role of sex hormones in regulating arterial ion channel function. This review covers key findings describing the current understanding of sex hormone regulation of vascular potassium channels, with a focus on KV7 channels. Further, we highlight areas of research where the estrus cycle should be considered in future studies to determine the consequences of physiological oscillations in concentrations of sex hormones on vascular potassium channel function.

From 1917 to 1962, the United States Navy was America’s main contributor to the use of lighter-than-air vehicles, from small observational kite-balloons to the massive infamous rigid airships like the ill-fated Shenandoah, Akron, and Macon. Most aviation histories cover the Navy’s rigid airships but ignore the post-rigid era, a period that began after the demise of the Hindenburg. This study serves to examine the Navy’s airship program in the subsequent two time periods: World War II and the post-war era. This study is based upon both qualitative and quantitative sources, most of which come from written accounts and statistics recorded during the subject’s time frame, making the study mostly reliant upon primary sources. Through the examination and analysis of these sources, this study shows that Navy blimps were a valuable contribution to merchant convoy defense during the Battle of the Atlantic, and that blimps’ performance and strengths enabled them to be valuable aircraft to the Navy even in the jet age.

ABSTRACT The ankyrin proteins (Ankyrin-R, Ankyrin-B, and Ankyrin-G) are a family of scaffolding, or membrane adaptor proteins necessary for the regulation and targeting of several types of ion channels and membrane transporters throughout the body. These include voltage-gated sodium, potassium, and calcium channels in the nervous system, heart, lungs, and muscle. At these sites, ankyrins recruit ion channels, and other membrane proteins, to specific subcellular domains, which are then stabilized through ankyrin’s interaction with the submembranous spectrin-based cytoskeleton. Several recent studies have expanded our understanding of both ankyrin expression and their ion channel binding partners. This review provides an updated overview of ankyrin proteins and their known channel and transporter interactions. We further discuss several potential avenues of future research that would expand our understanding of these important organizational proteins.

Background and Introduction: HIV is one of the most problematic pandemics to date, currently infecting upwards of 38 million people worldwide (“The Global HIV/AIDS Epidemic,” 2020). Although infection and mortality rates have generally decreased, current prophylactic (preventive) measures against HIV-1 acquisition have shown major weaknesses that could be remedied with a vaccine (Pitisuttuthum & Marovich, 2020). Manufacturing an effective, prophylactic HIV-1 vaccine, however, is not without challenges - namely design/selection of vaccine-delivered immunogens (antigens) and elicitation of proper immune responses to HIV-1 antigens (Ng’uni et al., 2020). Fortunately, despite past, unsuccessful research, studies within the past 10-15 years have begun to elucidate immune correlates of protection against HIV-1 acquisition, specifically IgG1/IgG3 antibody (Ab) production, as well as non-neutralizing, Fc-Mediated effector functions (Rerks-Ngarm et al., 2009). Excitingly, studies released in the last 3 years, which use Adenovirus serotype-26 (Ad26) vector (Custers et al., 2020) show promising signs that an effective HIV-1 vaccine could become a reality (Baden et al., 2020; Barouch et al., 2018). Thus, for this presentation, I hope to show that Johnson & Johnson’s two new Ad26-based vaccines (combined with booster vaccines) sufficiently elicit key immune correlates of protection to warrant an Ad26 vector-based regimen’s testing past Phase 1/2a clinical trials. Results and Conclusions: Recent studies that demonstrate the abilities of an Ad26-based vaccine regimen to elicit key immune correlates of protection (while remaining generally safe) are the APPROACH and TRAVERSE studies. From the APPROACH study, it’s demonstrated that a regimen consisting of two Ad26 priming injections, followed by two Ad26 boosting injections and two subunit boosting injections (Ad26/Ad26 + HD gp140), elicits more IgG1/IgG3 Abs and ADCP (antibody-dependent cellular phagocytosis) when compared to six alternative candidate regimens. Additionally, when this Ad26/Ad26 + HD gp140 regimen was administered to rhesus macaques, a 94% reduction in disease acquisition was observed (Barouch et al., 2018). Building off of the APPROACH study, the TRAVERSE study demonstrates the effects on immunogenicity when the Ad26 vector’s valency is increased. Increase in valency resulted in increased IgG1/IgG3 Ab production, as well as increased phagocytosis.. Promisingly, the breadth of HIV-1 antigens recognized by IgG1/IgG3 Abs also increased when vaccine valency increased as well (Baden et al., 2020). From the results of these two studies then, and the researchers’ conclusions from them, it seems appropriate to advance these two new Ad26-based regimens into further clinical trials (Phase 2 and 3).

ABSTRACT N-methyl-D-aspartate receptors (NMDARs) are excitatory ionotropic glutamate receptors expressed throughout the CNS, including in the spinal dorsal horn. The GluN2 subtypes of NMDAR subunit, which include GluN2A, GluN2B, and GluN2D in the dorsal horn, confer NMDARs with structural and functional variability, enabling heterogeneity in synaptic transmission and plasticity. Despite essential roles for NMDARs in physiological and pathological pain processing, the distribution and function of these specific GluN2 isoforms across dorsal horn laminae remain poorly understood. Surprisingly, there is a complete lack of knowledge of GluN2 expression in female rodents. We, therefore, investigated the relative expression of specific GluN2 variants in the dorsal horn of lumbar (L4/L5) spinal cord from both male and female rats. In order to detect synaptic GluN2 isoforms, we used pepsin antigen-retrieval to unmask these highly cross-linked protein complexes. We found that GluN2B and GluN2D are preferentially localized to the pain-processing superficial regions of the dorsal horn in males, while only GluN2B is predominantly localized to the superficial dorsal horn of female rats. The GluN2A subunit is diffusely localized to neuropil throughout the dorsal horn of both males and females, while GluN2B and GluN2D immunolabelling are found both in the neuropil and on the soma of dorsal horn neurons. Finally, we identified an unexpected enhanced expression of GluN2B in the medial division of the superficial dorsal horn, but in males only. These sex-specific localization patterns of GluN2-NMDAR subunits across dorsal horn laminae have significant implications for the understanding of divergent spinal mechanisms of pain processing.

The intertwinement of mother-daughter psyches throughout the early developmental process bonds maternal and filial parties up unto differentiation, at which point the child comes to understand her status as an individual and her mother’s status as a separate entity. However, when trauma is introduced midway through the differentiation process, this psychological phenomenon may be hindered, stunting the advanced personal development of the daughter. Abandoned by loss, she may subconsciously fall victim to repressive defenses, insufficient socialization, and destructive behaviors. In his 2016 novel Neverhome, Laird Hunt explores these psychological factors through a traumatized and unreliable female protagonist situated in the historical context of the early Civil War. A theoretically critical reading of Hunt’s text exposes the possible psychological tendencies of one such woman through a fictionalized narrative. Authoring plentiful examples of trauma responses, Hunt constructs his protagonist to serve as an archetype of the undifferentiated, unsocialized, and repressively-hindered daughter, and he then places her in a variety of high-stress environments within the plot to highlight her trauma-derived responses.

ABSTRACT Estradiol regulates thyroid function, and chloride channels are involved in the regulation of thyroid function. However, little is known about the role of chloride channels in the regulation of thyroid functions by estrogen. In this study, the effects of estrogen on chloride channel activities in human thyroid Nthy-ori3-1 cells were therefore investigated using the whole cell patch-clamp technique. The results showed that the extracellular application of 17β-estradiol (E2) activated Cl− currents, which reversed at a potential close to Cl− equilibrium potential and showed remarkable outward rectification and an anion permeability of I− > Br− > Cl− > gluconate. The Cl− currents were inhibited by the chloride channel blockers, NPPB and tamoxifen. Quantitative Real-time PCR results demonstrated that ClC-3 expression was highest in ClC family member in Nthy-ori3-1 cells. The down-regulation of ClC-3 expression by ClC-3 siRNA inhibited E2-induced Cl− current. The Cl− current was blocked by the estrogen receptor antagonist, ICI 182780 (fulvestrant). Estrogen receptor alpha (ERα) and not estrogen receptor beta was the protein expressed in Nthy-ori3-1 cells, and the knockdown of ERα expression with ERα siRNA abolished E2-induced Cl− currents. Estradiol can promote the accumulation of ClC-3 in cell membrane. ERα and ClC-3 proteins were partially co-localized in the cell membrane of Nthy-ori3-1 cells after estrogen exposure. The results suggest that estrogen activates chloride channels via ERα in normal human thyroid cells, and ClC-3 proteins play a pivotal role in the activation of E2-induced Cl− current.

ABSTRACT Endocannabinoids are a group of endogenous mediators derived from membrane lipids, which are implicated in a wide variety of physiological functions such as blood pressure regulation, immunity, pain, memory, reward, perception, reproduction, and sleep. N-Arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG) represent two major endocannabinoids in the human body and they exert many of their cellular and organ system effects by activating the Gi/o protein-coupled, cannabinoid type 1 (CB1) and type 2 (CB2) receptors. However, not all effects of cannabinoids are ascribable to their interaction with CB1 and CB2 receptors; indeed, macromolecules like other types of receptors, ion channels, transcription factors, enzymes, transporters, and cellular structure have been suggested to mediate the functional effects of cannabinoids. Among the proposed molecular targets of endocannabinoids, potassium channels constitute an intriguing group, because these channels not only are crucial in shaping action potentials and controlling the membrane potential and cell excitability, thereby regulating a wide array of physiological processes, but also serve as potential therapeutic targets for the treatment of cancer and metabolic, neurological and cardiovascular disorders. This review sought to survey evidence pertaining to the CB1 and CB2 receptor-independent actions of endocannabinoids on ion channels, with an emphasis on AEA and potassium channels. To better understand the functional roles as well as potential medicinal uses of cannabinoids in human health and disease, further mechanistic studies to delineate interactions between various types of cannabinoids and ion channels, including members in the potassium channel superfamily, are warranted.