Paradoxical Role Research Articles

Paradoxical role of structural degradation of nickel-rich layered oxides in capacity retention upon storage of lithium-ion batteries

The storage-induced aging mechanism is comprehensively demonstrated. Prolonged idle storage of a Li-ion battery triggered a unique degradation process of layered oxide cathodes, which played a paradoxical role in capacity retention.

Habitat determinants of species occupancy and niche partitioning among sympatric owlets: the paradoxical role of agricultural lands for the endangered Forest Owlet, Athene blewitti

Species with highly restricted distributions are intriguing especially when they co-occur with similar and related species that are more widely distributed. They are also of conservation concern because of their restricted distributions and low population size. The Forest Owlet (<em>Athene blewitti</em>) is an endangered species endemic to the central Indian landscape that occurs in apparently unconnected pockets. Two other species of owlets, with wide distributions in India, Jungle Owlet (<em>Glaucidium radiatum</em>) and Spotted Owlet (<em>Athene brama</em>) co-occur with Forest Owlet. Understanding how species use the habitat matrix is central to prioritizing conservation action. We studied the three species across an extensive part of the predicted range of Forest Owlets through 350 surveys. Our results indicate that Jungle Owlet occupancy (ψ = 0.5896, SE = 0.08) was highest, followed by Forest Owlet (ψ = 0.2517, SE = 0.10), and Spotted Owlet (ψ = 0.1781, SE = 0.07). The Forest Owlet showed a preference for stands of forests with large trees but not necessarily with closed canopies, as well as open habitats (agricultural land cover). The Spotted Owlet showed a preference for agricultural land cover with lower litter and bare ground cover. In contrast, the Jungle Owlet showed a preference for dense forest and canopy cover. The preference for agricultural cover by the Forest Owlet provides important insights into our understanding of the ecology of this owlet. Most significantly, it brings up several conservation challenges for managing this endangered species across a human-use landscape.

Characterization of cellular senescence patterns predicts the prognosis and therapeutic response of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a prevalent malignancy with a high mortality rate. Cellular senescence, an irreversible state of cell cycle arrest, plays a paradoxical role in cancer progression. Here, we aimed to identify Hepatocellular carcinoma subtypes by cellular senescence-related genes (CSGs) and to construct a cellular senescence-related gene subtype predictor as well as a novel prognostic scoring system, which was expected to predict clinical outcomes and therapeutic response of Hepatocellular carcinoma. Methods: RNA-seq data and clinical information of Hepatocellular carcinoma patients were derived from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). The "multi-split" selection was used to screen the robust prognostic cellular senescence-related genes. Unsupervised clustering was performed to identify CSGs-related subtypes and a discriminant model was obtained through multiple statistical approaches. A CSGs-based prognostic model-CSGscore, was constructed by LASSO-Cox regression and stepwise regression. Immunophenoscore (IPS) and Tumor Immune Dysfunction and Exclusion (TIDE) were utilized to evaluate the immunotherapy response. Tumor stemness indices mRNAsi and mDNAsi were used to analyze the relationship between CSGscore and stemness. Results: 238 robust prognostic differentially expressed cellular senescence-related genes (DECSGs) were used to categorize all 336 hepatocellular carcinoma patients of the TCGA-LIHC cohort into two groups with different survival. Two hub genes, TOP2A and KIF11 were confirmed as key indicators and were used to form a precise and concise cellular senescence-related gene subtype predictor. Five genes (PSRC1, SOCS2, TMEM45A, CCT5, and STC2) were selected from the TCGA training dataset to construct the prognostic CSGscore signature, which could precisely predict the prognosis of hepatocellular carcinoma patients both in the training and validation datasets. Multivariate analysis verified it as an independent prognostic factor. Besides, CSGscore was also a valuable predictor of therapeutic responses in hepatocellular carcinoma. More downstream analysis revealed the signature genes were significantly associated with stemness and tumor progression. Conclusion: Two subtypes with divergent outcomes were identified by prognostic cellular senescence-related genes and based on that, a subtype indicator was established. Moreover, a prognostic CSGscore system was constructed to predict the survival outcomes and sensitivity of therapeutic responses in hepatocellular carcinoma, providing novel insight into hepatocellular carcinoma biomarkers investigation and design of tailored treatments depending on the molecular characteristics of individual patients.

The paradoxical relationship between sense of power and creativity: Countervailing pathways and a boundary condition

AbstractWhen sense of power helps or hinders creativity remains an unresolved question. Drawing upon the approach‐inhibition theory of power and its extensions, we integrate two different predictions into a dual‐pathway model, showing the paradoxical role that sense of power—one's perceived ability to influence others—plays in predicting creativity. Specifically, sense of power helps creativity through increased risk‐taking and simultaneously hinders it through reduced perspective taking. We further propose openness to experience as a moderator of the countervailing mechanisms, such that the positive path through risk‐taking is stronger and the negative path through perspective taking is weaker for individuals with higher (vs. lower) levels of openness. We test our hypotheses with three multisource and multi‐wave field studies (Study 1: n = 181 part‐time MBAs paired with peers; Study 2: n = 128 sales employees paired with store managers; Study 3: n = 153 sales employees paired with store managers). The results support our theoretical model, showing that sense of power and creativity are simultaneously connected positively through risk‐taking and negatively through perspective taking, and that the overall indirect effect of sense of power on creativity is more positive for individuals with higher (vs. lower) levels of openness to experience.

Understanding change in disruptive contexts: The role of the time paradox and locus of control

We examine how the experience of time and locus of control influence organizational change in disruptive contexts. Through the cycles of the COVID-19 pandemic restrictions and their relaxations in Turkey, we found that organizations approached change similarly in the short term but differently in the long term. To unpack the mechanism behind these observations, we analyzed in-depth qualitative data from five organizations from March 2020 to September 2021. We reveal that the change process creates time pressure in disruptive contexts, and a time paradox emerges to the extent that the change outcomes increase the available time under time pressure. Depending on their locus of control, individuals either complement organizational change or resist it even more after triggering events that signal the lastingness of the post-disruption situation. Our framework may enhance organizational resilience to future disruptions by highlighting the requirement for change recipients to make complementary moves to regain control.

The Strategic and Paradoxical Usage of Phenomenology in Foucault’s Archaeology

Abstract It is well-known that the mature Foucault, while recognizing the influence of phenomenology on him during his youth, declared his anti-phenomenological position since his archeological breakthrough. This paper tries to argue and show that though phenomenology is an object of criticism of Foucault’s archaeology, it nonetheless plays a paradoxical and strategic role in the construction of the archaeological project. Though Foucault undertakes in The Birth of the Clinic a critical deconstruction of phenomenology as positivism, against the open anti-positivist declaration of phenomenology itself, in the Archeology of Knowledge Foucault acknowledges that the opening of the space of archeology requires the practice of the “épochè of the épochè”, and in this sense archeology is a positivism too. That means also that archeology is possible only by the practice of the phenomenological operation of épochè in order to exit from phenomenology. This paradoxical and strategic usage of phenomenology in Foucault’s archeology is extended to his theory of discourse. For Foucault came to realize the limit of discursive practice: not only words signify but things signify too. If archeology wants to extend its domain of competence, it has to recur to description according to the way things show up themselves. This is nothing other than the basic methodological recommendation of phenomenology. Thus Foucault’s open declaration of his anti-phenomenological position is merely apparent, hiding his discrete paradoxical and strategic usage of the rich methodological resources of phenomenology.

Tipping the balance: New insights into stromal regulation of cancer.

Desmoplastic extracellular matrix (ECM) exerts a seemingly paradoxical role in cancer, restricting or promoting progression. Two recent back-to-back Nature reports shed light on this conundrum, revealing the role of different hepatic stellate cell (HSC) populations and different collagen I cleavage states in directing the progression of cancer.

Inosine, gut microbiota, and cancer immunometabolism.

This article briefly reviews cancer immunity and the role of gut microbiota in carcinogenesis, followed by an understanding of mechanisms by which inosine is involved in cancer immunometabolism. The immune system plays a paradoxical role in cancer treatment. Antitumor immunity depends on the T-cell priming against tumor antigens, whereas inflammatory mediators trigger the protumor signaling in the tumor microenvironment. Studies link the microbiome with metabolism and immunity-two main factors implicated in carcinogenesis. Gut microbiota has been shown to affect both antitumor immunity and protumor immune signaling. There is mounting evidence that the human microbiome can play a role in the immunotherapeutic effects, both response and resistance. Inosine-5'-monophosphate dehydrogenase (IMPDH) is a highly conservative enzyme widely expressed in mammals. Cell signaling pathways use molecular inosine, a crucial secondary metabolite in purine metabolism and a molecular messenger. Recent research has identified inosine as a critical regulator of immune checkpoint inhibition (ICI) therapeutic response in various tumor types. Some bacterial species were found to produce inosine or its metabolite hypoxanthine and induce T-helper 1 differentiation and effector functions via the inosine-A2AR-cAMP-PKA pathway upon ICI therapy. Also, inosine acts as a substitute carbon source for T-cell metabolism in glucose-restricted environments, i.e., the tumor microenvironment, assisting T-cell proliferation and differentiation while enhancing sensitivity to ICI, reinforcing the notion that inosine metabolism might contribute to antitumor immunity. Also, inosine is a potent agonist of the adenosine receptor, A2AR, and A2AR signaling can affect T-cell responses and antitumor immunity, making the inosine-A2AR pathway blockage a candidate for cancer treatment. Further research is required to investigate inosine as a cancer immunometabolism therapy.

MTOR inhibition attenuates chemosensitivity through the induction of chemotherapy resistant persisters

Chemotherapy can eradicate a majority of cancer cells. However, a small population of tumor cells often survives drug treatments through genetic and/or non-genetic mechanisms, leading to tumor recurrence. Here we report a reversible chemoresistance phenotype regulated by the mTOR pathway. Through a genome-wide CRISPR knockout library screen in pancreatic cancer cells treated with chemotherapeutic agents, we have identified the mTOR pathway as a prominent determinant of chemosensitivity. Pharmacological suppression of mTOR activity in cancer cells from diverse tissue origins leads to the persistence of a reversibly resistant population, which is otherwise eliminated by chemotherapeutic agents. Conversely, activation of the mTOR pathway increases chemosensitivity in vitro and in vivo and predicts better survival among various human cancers. Persister cells display a senescence phenotype. Inhibition of mTOR does not induce cellular senescence per se, but rather promotes the survival of senescent cells through regulation of autophagy and G2/M cell cycle arrest, as revealed by a small-molecule chemical library screen. Thus, mTOR plays a causal yet paradoxical role in regulating chemotherapeutic response; inhibition of the mTOR pathway, while suppressing tumor expansion, facilitates the development of a reversible drug-tolerant senescence state.

UNFOLDING THE REALITY OF SMOKING PARADOX IN PATIENTS PRESENTING WITH STE-ACS UNDERGOING PRIMARY PERCUTANEOUS CORONARY TREATMENT

Objectives: Main objective for this study to unfold this controversy in South Asian population in terms of clinical, angiographic parameters and its in-hospital outcomes.&#x0D; Methodology: In this study, we included 1756 consecutive patients diagnosed with STEMI undergoing primary PCI. Patients were classified into smokers and nonsmokers. Comparison was done on the basis of baseline characteristics, clinical presentation, angiographic features and in-hospital mortality between two groups. Multivariable logistic regression analysis was performed to evaluate the paradoxical role of smoking.&#x0D; Results: Smokers were younger (53.78±11.16 years vs. 56.43±11.17 years; p&lt;0.001) and more frequently male (98.7% vs. 69.9%; p&lt;0.001), and had less diabetes (19.6% vs. 44.8%; p&lt;0.001) and hypertension (38.5% vs. 64.9%; p&lt;0.001). Smokers presented less frequently in Killip III (5.6% vs. 8.1%; p&lt;0.001) and Killip IV (2.5% vs. 4.8%; p&lt;0.001) in smokers group. Smokers mostly had single vessel disease (41.7% vs. 34.4%; p=0.013) whereas non-smokers had complex disease and frequently presented with total occlusion of the culprit vessel (64.6% vs. 58.8%; p=0.040). Complication such as slow flow/no-flow (24.3% vs. 33.2%; p&lt;0.001) and cardiogenic shock (2.3% vs. 4.6%; p&lt;0.001) were also seen less often among smokers. Smokers has significantly lesser mortality (1.8% vs. 4.3%; p=0.009) compared to non-smokers with an odds ratio (OR) of 0.41 [95% CI: 0.21-0.82, p=0.011], however, adjusted OR on multivariable analysis was 0.67 [95% CI: 0.31-1.41, p=0.290]. Independent predictors of mortality were found to be history of CVA/stroke, pre-procedure LVEDP, multi-vessel diseases, and RBS in ER adjusted OR of 3.83 [95% CI: 1.24-11.79; p=0.019], 1.07 [95% CI: 1.03-1.12; p=0.002], 2.2 [95% CI: 1.07-4.54; p=0.033], and 1 [95% CI: 1.0-1.01; p=0.032], respectively.&#x0D; Conclusion: The controversial phenomenon of smoking paradox seems to be unfolded in South Asian population in post STE-ACS patients. The paradoxical protective role of smoking is confounding effect of mainly younger age, less coronary artery disease burden and complexity, lower prevalence of diabetes and hypertension and lower rate of Killip III/IV at presentation. Hence, the protective effect is insignificant in multivariable analysis and history of CVA/stroke, pre-procedure LVEDP, multi-vessel diseases, and RBS in ER were found to be independent predictors of in-hospital mortality.

Gout as a risk factor for osteoporosis: A Korean population-based study.

Uric acid acts as both an antioxidant and a pre-oxidant that induces oxidative stress; thus, it plays a paradoxical role in inflammation. However, the effect of gout, a hallmark of hyperuricemia, on osteoporosis remains unclear. Therefore, this study aimed to investigate the association between gout and osteoporosis. This retrospective cohort study used data from the Korean National Health Insurance Service Database. In total, 628,565 participants who were diagnosed with gout and prescribed medications for gout for at least 90 days were selected. The control cohort included patients with no history of gout or use of gout medication. Age and sex 1:1 propensity score matching and Cox proportional hazards models were used to investigate risk factors for osteoporosis. In total, 305,810 patients with gout met the inclusion criteria. Compared with the control group, both men and women with gout showed an increased incidence rate ratio of osteoporosis. In the stratified analysis by age, patients with gout showed an increased incidence rate ratio for osteoporosis in all age groups, except for those over 80 years of age (P < .001). Gout showed an increased hazard ratio of 1.48 (95% CI: 1.45-1.51, P < .001). The female sex has also been identified as a risk factor for osteoporosis. Patients in their 70s had the highest HR. Gout is significantly associated with the risk of osteoporosis. In particular, the results of this study showed that the incidence of osteoporosis increased up to four times in male patients in their 20s with gout compared to without gout.

Abstract 13332: Obesity Paradox in Stress Cardiomyopathy When Comparing Outcomes

Introduction:Stress Cardiomyopathy (SCM), is an acute reversible myocardial injury associated with transient left ventricular dysfunction. Risk factors include female sex, post-menopause, anxiety, depression, schizophrenia, asthma and chronic obstructive pulmonary disease, diabetes, and substance use. Obesity has an increased sympathetic tone and state of chronic metabolic stress, both of which are similar in etiology to SCM. We postulate that obesity may have high prevalence in patients with SCM. Methods: We queried the Nationwide Inpatient Sample database (2016-2019) to identify adult patients with SCM with and without obesity, along with other common co-morbidities using ICD-10 codes. We compared the categorical and continuous variables by Pearson χ2 and Student t test. Results: There were 31,725 patients with SCM. The mean age was 67.15 + 14 years and the population was predominately female, n=26409 (83.2%). Racial distribution consisted of White (n=24713 77.9%), Black (n=24713, 8%), and Hispanic (n=1918, 6%). There were 3816 (12%) who were diagnosed with obesity. When comparing both groups, obese patients were found to be younger than non-obese, 63.3 + 14 years vs. 67.68 + 13 years, p&lt;0.001, respectively. Obese patients had higher incidences of hypertension (n=10317; 38.9% vs. 1485; 37%, p=0.005), chronic kidney disease (n=3874; 17.5% vs. n=668; 13.9%, p&lt;0.001), dyslipidemia (n=1771; 46.4% vs. n=10625; 38.1%, p &lt;0.001), diabetes mellitus (n=373; 9.8% vs n=1278; 4.6%, p&lt;0.001), non-alcoholic fatty liver disease (n=30; 0.8% vs. n=68; 0.2%, p&lt;0.001), and polycystic ovarian syndrome (n= 30; 0.8% vs n=68; 0.2%, p&lt;0.001). Tobacco use was higher in non-obese vs. obese patients (n=311; 1.1% vs. 28; 0.7%, p=0.32). The length of stay for both groups was similar, 7-days. Obese patients had a lower total hospital charges ($95,098 vs. $98,735). There was a lower incidence of mortality among obese patients n=194 (5.1%) vs. non-obese n=1743 (6.2%), p&lt;0.005. Conclusion: Despite obese patients having more risk factors for developing SCM than non-obese patients, they were found to have decreased mortality and a lower cost of stay. These findings suggest that obesity may play a paradoxical role in SCM.

Anatomical location of injected microglia in different activation states and time course of injury determines survival of retinal ganglion cells after optic nerve crush

Background: Activated microglia release harmful substances to retinal ganglion cells (RGCs), but may also benefit by removing cellular debris and secreting neurotrophic factors. These paradoxical roles remain controversial because the nature and time-course of the injury that defines their role is unknown. The aim of this study was to determine if pharmacological manipulation of microglia to acquire a pro-inflammatory or pro-survival phenotype will exacerbate or enhance neuronal survival after injury.Material and methods: Treated HAP I (highly aggressively proliferating immortalized) microglia were injected into the vitreous or tail vein (T V) of female Sprague-Dawley rats. Retinas were examined at 4-14 days following optic nerve crush (ONC) and the number of surviving RGCs was determined.Results: Injection of untreated HAP I cells resulted in the greater loss of RGCs early after ONC when injected into the vitreous and later after ONC when injected into the T V. LP S activated HAP I cells injected into the vitreous resulted in greater RGC loss with and without injury. When injected into the T V with ONC there was no loss of RGCs 4 days after ONC but greater loss afterwards. Minocycline treated HAP I cells injected into the vitreous resulted in greater RGC survival than untreated HAP I cells. However, when injected into the T V with ONC there was greater loss of RGCs. These results suggest that optic nerve signals attract extrinsic microglia to the retina, resulting in a proinflammatory response.Conclusion: Neuroprotection or cytotoxicity of microglia depends on the type of activation, time course of the injury, and if they act on the axon or cell body.

Tensions and outcomes in corporate sustainability: The moderating role of paradoxical frame

Tensions are an unavoidable experience for companies dealing with social and environmental issues because of their inherent complexity and diversity. Paradox and sustainability literature are proposing the crucial role of cognitive frames in effectively managing sustainability tensions. Indeed, denying and suppressing them can spur vicious downward spirals that paralyze actions, reduce their effectiveness, or lead to unintended consequences. On the contrary, recognizing the interrelation and the persistence of opposing sustainability elements and accepting the inherent conflicts can generate virtuous cycles, where the potential of these tensions is released and superior outcomes achieved. Existing literature is providing the first qualitative empirical evidence regarding the potential of a paradoxical cognitive frame for corporate sustainability. However, research on the role of paradox as organizational cognitive frame in fostering sustainability outcomes is still underdeveloped, and moreover, quantitative research to make such evidence more generalizable is missing. Therefore, this study aims at quantitatively investigating whether organizations embracing paradox as collective frame – i.e. accepting contradictions by accommodating competing yet interrelated elements simultaneously, and continuously integrating them – to address sustainability tensions are able to improve their sustainability outcomes – i.e., going beyond compliance in limiting their impact on social and natural systems and preventing social and environmental crises. Based on original survey data regarding how firms perceived the experience of sustainability tensions, how they frame such tensions, and how they perceived their social, environmental, and financial outcomes, results reveal that framing sustainability tensions as paradoxes fosters firms' social and environmental outcomes; however, they also highlight the limitations of this approach. Indeed, a paradoxical organizational cognitive frame supports companies in achieving higher social and environmental outcomes, but not economic ones. Thus, this research contributes to paradox literature by providing a better understanding of the role and the nature of paradox as potential organizational frame to cope with sustainability complexity.

Systematic analysis of the MAPK signaling network reveals MAP3K-driven control of cell fate.

The classic network of mitogen-activated protein kinases (MAPKs) is highly interconnected and controls a diverse array of biological processes. In multicellular eukaryotes, the MAPKs ERK, JNK, and p38 control opposing cell behaviors but are often activated simultaneously, raising questions about how input-output specificity is achieved. Here, we use multiplexed MAPK activity biosensors to investigate how cell fate control emerges from the connectivity and dynamics of the MAPK network. Through chemical and genetic perturbation, we systematically explore the outputs and functions of all the MAP3 kinases encoded in the human genome and show that MAP3Ks control cell fate by triggering unique combinations of MAPK activity. We show that these MAPK activity combinations explain the paradoxical dual role of JNK signaling as pro-apoptotic or pro-proliferative kinase. Overall, our integrative analysis indicates that the MAPK network operates as a unit to control cell fate and shifts the focus from MAPKs to MAP3Ks to better understand signaling-mediated control of cell fate.

Physiology of chemokines in the cancer microenvironment.

Chemokines are chemotactic cytokines whose canonical functions govern movement of receptor-expressing cells along chemical gradients. Chemokines are a physiological system that is finely tuned by ligand and receptor expression, ligand or receptor oligomerization, redundancy, expression of atypical receptors, and non-GPCR binding partners that cumulatively influence discrete pharmacological signaling responses and cellular functions. In cancer, chemokines play paradoxical roles in both the directed emigration of metastatic, receptor-expressing cancer cells out of the tumor as well as immigration of tumor-infiltrating immune cells that culminate in a tumor-unique immune microenvironment. In the age of precision oncology, strategies to effectively harness the power of immunotherapy requires consideration of chemokine gradients within the unique spatial topography and temporal influences with heterogeneous tumors. In this article, we review current literature on the diversity of chemokine ligands and their cellular receptors that detect and process chemotactic gradients and illustrate how differences between ligand recognition and receptor activation influence the signaling machinery that drives cellular movement into and out of the tumor microenvironment. Facets of chemokine physiology across discrete cancer immune phenotypes are contrasted to existing chemokine-centered therapies in cancer.

The paradoxical role of radiation-induced cGAS-STING signalling network in tumour immunity.

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an essential component of the innate immune system and is central to the identification of abnormal DNA leakage caused by ionising radiation (IR) damage. Cell-intrinsic cGAS-STING initiation has been revealed to have tremendous potential for facilitating interferon synthesis and T-cell priming. Targeting the cGAS-STING axis has been proposed as a strategy to improve radiosensitivity or enhance immunosurveillance. However, due to the complex biology of the irradiated tumour microenvironment and the extensive involvement of the cGAS-STING pathway in various physiological and pathological processes, many defects in this strategy limit the therapeutic effect. Here, we outline the molecular mechanisms by which IR activates the cGAS-STING pathway and analyse the dichotomous roles of the cGAS-STING pathway in modulating cancer immunity after radiotherapy (RT). Then, based on the crosstalk between the cGAS-STING pathway and other signalling events induced by IR, such as necroptosis, autophagy and other cellular effects, we discuss the immunomodulatory actions of the broad cGAS-STING signalling network in RT and their potential therapeutic applications. Finally, recent advances in combination therapeutic strategies targeting cGAS-STING in RT are explored.

Examining the role of EGR1 during viral infections.

Early growth response 1 (EGR1) is a multifunctional mammalian transcription factor capable of both enhancing and/or inhibiting gene expression. EGR1 can be activated by a wide array of stimuli such as exposure to growth factors, cytokines, apoptosis, and various cellular stress states including viral infections by both DNA and RNA viruses. Following induction, EGR1 functions as a convergence point for numerous specialized signaling cascades and couples short-term extracellular signals to influence transcriptional regulation of genes required to initiate the appropriate biological response. The role of EGR1 has been extensively studied in both physiological and pathological conditions of the adult nervous system where it is readily expressed in various regions of the brain and is critical for neuronal plasticity and the formation of memories. In addition to its involvement in neuropsychiatric disorders, EGR1 has also been widely examined in the field of cancer where it plays paradoxical roles as a tumor suppressor gene or oncogene. EGR1 is also associated with multiple viral infections such as Venezuelan equine encephalitis virus (VEEV), Kaposi's sarcoma-associated herpesvirus (KSHV), herpes simplex virus 1 (HSV-1), human polyomavirus JC virus (JCV), human immunodeficiency virus (HIV), and Epstein-Barr virus (EBV). In this review, we examine EGR1 and its role(s) during viral infections. First, we provide an overview of EGR1 in terms of its structure, other family members, and a brief overview of its roles in non-viral disease states. We also review upstream regulators of EGR1 and downstream factors impacted by EGR1. Then, we extensively examine EGR1 and its roles, both direct and indirect, in regulating replication of DNA and RNA viruses.

Marginal SARS-CoV-2 Spike Protein Increases Interferon and Balances Cytokine Gene Expression

Some evidence confirms the paradoxical beneficial role of harmful antigens when used in highly diluted forms. In this experiment, we observed cytokine gene expression changes in Gallus gallus embryo after challenge with Delta SARS-CoV-2 RBD spike protein antigen, from a concentration of 10 µg/mL to a series of highly diluted forms in ethanol, along with controls. We have also studied pre-and post- experimental combined sets of higher (10 µg/mL) and significantly lower antigen concentrations (attogram level). Attogram and zeptogram level concentrations of the antigen showed consistently remarkable up-regulation of INF-α among different cytokine gene expressions. INF-β gene expressions at the zeptogram level of the antigen showed consistent changes, although not so outstanding. The pre-experimental set having attogram level antigen administered first, followed by a 10µg/mL antigen challenge, showed excellent cytokine balance. Other experimental groups, including the control sets, showed variable results at different concentrations.

Twilight of Human Judgment

Twilight of Human Judgment