PANoptosis: A New Insight Into Oral Infectious Diseases

The oral microbiome, one of the most complex and intensive microbial ecosystems in the human body, comprises bacteria, archaea, fungi, protozoa, and viruses. Dysbiosis of the oral microbiome is the initiating factor that leads to oral infectious diseases. Infection is a sophisticated biological process involving interplay between the pathogen and the host, which often leads to activation of programmed cell death. Studies suggest that pyroptosis, apoptosis, and necroptosis are involved in multiple oral infectious diseases. Further understanding of crosstalk between cell death pathways has led to pyroptosis, apoptosis, and necroptosis being integrated into a single term: PANoptosis. PANoptosis is a multifaceted agent of the immune response that has important pathophysiological relevance to infectious diseases, autoimmunity, and cancer. As such, it plays an important role in innate immune cells that detect and eliminate intracellular pathogens. In addition to the classical model of influenza virus-infected and Yersinia-infected macrophages, other studies have expanded the scope of PANoptosis to include other microorganisms, as well as potential roles in cell types other than macrophages. In this review, we will summarize the pathophysiological mechanisms underlying inflammation and tissue destruction caused by oral pathogens. We present an overview of different pathogens that may induce activation of PANoptosis, along with the functional consequences of PANoptosis in the context of oral infectious diseases. To advance our understanding of immunology, we also explore the strategies used by microbes that enable immune evasion and replication within host cells. Improved understanding of the interplay between the host and pathogen through PANoptosis will direct development of therapeutic strategies that target oral infectious diseases.

Deep Conservation of Hid-Like RHG Gene Family Homologs in Winged Insects Revealed by “Taxon Hopping” BLAST

Together with sickle (skl), the Drosophila paralogs reaper (rpr), head involution defective (hid), and grim (RHG) control a critical switch in the induction of programmed cell death. RHG homologs have been identified in other dipteran and lepidopteran species but not beyond. Revisiting this issue with a “taxon hopping” BLAST search strategy in current genome and transcriptome resources, I detected high confidence RHG homologs in Coleoptera, Hymenoptera, Hemiptera, and Dictyoptera. Analyses of gene structure and protein sequence conservation revealed aconserved splicing pattern and highly conserved amino acid residues at both the N- and C-terminal ends that identify hid as the most ancestrally organized RHG gene family member in Drosophila. hid-like RHG homologs were also detected in mosquitoes, redefining their michelob_x (mx) genes as an expansion of derived RHG homologs. Only singleton homologs were detected in the large majority of other insect clades. Lepidopteran RHG homologs, however, stand out by producing an evolutionarily-derived splice isoform, identified in previous work, in addition to the newly detected hid-like isoform. Exceptional sequence diversification of select RHG homologs at the family- and genus-level explain their previous elusiveness in important insect genome model species like the red flour beetle Tribolium castaneum and the pea aphid Acyrthosiphon pisum. Combined, these findings expand the minimal age of the RHG gene family by about 100 million years and open new avenues for molecular cell death studies in insects.

The Impact of Obesity on SARS-CoV-2 Pandemic Mortality Risk

The COVID-19 pandemic has uncovered the increased susceptibility of individuals with obesity to infection and severe disease leading to hospitalization and death. Studies in New York City demonstrated that after advanced age, obesity was the most common risk factor leading to severe disease and death from COVID-19. While the connection has been recognized, there has not been a general recognition of the potential mechanisms for this link between excess body fat and mortality from this viral pandemic including respiratory complications and sequelae of increased activation of the immune system. Despite plans for vaccination of the global population, the risk community spread of COVID-19 and future pandemics will be linked in part to obesity and immunity. This review will detail a number of potential mechanisms through which obesity may contribute to the lethality of this viral infection. These insights will hopefully lead to a greater emphasis on obesity prevention and treatment as part of the global response to this and future pandemic threats.

Bifurcation Analysis on a Generation of Early Afterdepolarization in a Mathematical Cardiac Model

Electrical activity occurs in the cell membrane of cardiomyocytes. This electrical activity forms the action potential that generates pumping of the heart. An abnormality in the action potential turns into arrhythmia, which may cause sudden death. Studies of arrhythmias using mathematical models are important to reduce the risk of sudden death. In this study, we investigate bifurcations related to the generation of early afterdepolarizations (EADs) in a mathematical model. We clarify the transition process from a normal state to a persistent EAD through a transient EAD while changing only one parameter (multiple of conductance of L-type calcium channel current) value. The dependence of the transient EAD generation on parameters is shown through bifurcation analysis in a [Na]i-parameterized system.

Green Banana mixed Diet is Beneficial in the Management of Childhood Persistent Diarrhea: an Open, Randomized-Controlled Trial (Preprint)

BACKGROUND Persistent diarrhea (PD), diarrhea for ≥14 days, accounts for 36%-56% of all diarrhea-related death. Studies demonstrated that green banana helps in the resolution of diarrhea. OBJECTIVE We assessed whether a lactose-free diet rice suji (RS) or rice suji containing green banana (GB-RS), improves outcome compared with 3/4th strength rice suji (3/4th RS) in 6 to 35 months old children having PD in the icddr,b Dhaka hospital. METHODS In this open-labeled, randomized, controlled trial, children with PD not improving with milk suji (the initial diet) received any of the three study diets: GB-RS, RS, 3/4th RS. The primary outcome was the percentage of children who recovered from diarrhea by day 5 with an intention to treat analysis. RESULTS From 1st December 2017 to 31st August 2019, we randomly allocated 45 children to each group. By day 5, 66 children recovered from PD, of whom 26 (58%), 14 (31%), 26 (58%) received GB-RS, RS, and 3/4th RS respectively. Significantly more resolution of PD occurred in GB-RS and 3/4th RS groups compared to RS group [relative risk (RR) 1⸱71, 95% CI 1⸱19-2⸱60; p=0⸱019]. Two (10%) children died, one each in RS group and GB-RS group. TaqMan array card (TAC) identified EAEC, rotavirus, norovirus, EPEC, astrovirus, and Campylobacter as the major pathogens associated with PD. CONCLUSIONS GB-RS and 3/4th RS are efficacious in the management of PD in young children. We also demonstrated a wide range of entero-pathogen associated with PD by TAC which needs further study to find a causal link. CLINICALTRIAL ClinicalTrials.gov, ID: NCT03366740 Registered on 8th December 2017 INTERNATIONAL REGISTERED REPORT RR2-10.2196/15759

Media, mortality and necro-technologies: Eulogies for dead media

Working at the intersection of death studies and media studies, this article examines what we can learn from the death of media technologies designed for the deceased, what we refer to as necro-technologies. Media deaths illuminate a tension between the promise of persistence and realities of precariousness embodied in all media. This tension is, however, more visibly strained by the mortality of technologies designed to mediate and memorialise the human dead by making explicit the limitations of digital eternity implied by products in the funeral industry. In this article, we historicise and define necro-technologies within broader discussions of media obsolescence and death. Drawing from our funeral industry fieldwork, we then provide four examples of recently deceased necro-technologies that are presented in the form of eulogies. These eulogies offer a stylised but culturally significant format of remembrance to create an historical record of the deceased and their life. These necro-technologies are the funeral attendance robot CARL, the in-coffin sound system CataCombo, the posthumous messaging service DeadSocial and the digital avatar service Virtual Eternity. We consider what is at stake when technologies designed to enliven the human deceased – often in perpetuity – are themselves subject to mortality. We suggest a number of entangled economic, cultural and technical reasons for the failure of necro-technologies within the specific contexts of the death care industry, which may also help to highlight broader forces of mortality affecting all media technologies. These are described as misplaced commercial imaginaries, cultural reticence and material impermanence. In thinking about the deaths of necro-technologies, and their causes, we propose a new form of death, a ‘material death’ that extends beyond biological, social and memorial forms of human death already established to account for the finitude of media materiality and memory.

Nonlocal Consciousness and the Anthropology of Religion

"Most discussions of religion center on dogmas and beliefs, either of a particular religion or a comparison across denomina- tions. I would like to look at religion from the perspective of a consciousness experimentalist, setting aside the dogmas and beliefs. When I look at religion, any religion, as an experimentalist, what I see is a cohort of people consensually holding a world- view. The process of assembling the cohort seems to me very much like Thomas Kuhn’s description of the paradigm process. The paradigm in religion is defined by scripture and dogma. The paradigms differ in many ways but they all have one thing in common. All are centered on the aspect of consciousness that in science we call nonlocal, and that is now being explicitly researched in near death studies, therapeutic intention work, and remote viewing. For me what is perhaps most interesting of all in studying both religions and the science of consciousness is that this is one of history’s great confluences, the practices of the religion and the practices of science have found common ground, and reached the same conclusions."

Deep conservation of Hid-like RHG gene family homologs in winged insects

ABSTRACTTogether with sickle (skl), the Drosophila paralogs reaper (rpr), head involution defective (hid), and grim (RHG) control a critical switch in the induction of programmed cell death. RHG homologs have been identified in other dipteran and lepidopteran species but not beyond. Revisiting this issue with a “taxon hopping” BLAST search strategy in current genome and transcriptome resources, I detected high confidence RHG homologs in Coleoptera (beetles), Hymenoptera (bees+wasps), Hemiptera (true bugs), termites, and cockroaches. Analyses of gene structure and protein sequence conservation revealed a shared ancestral splicing pattern and highly conserved amino acid residues at both the N- and C-terminal ends that identify hid as the most ancestrally organized RHG gene family member in Drosophila. hid-like RHG homologs were also detected in mosquitoes, redefining their michelob_x (mx) genes as an expansion of derived RHG homologs. Only singleton homologs were detected in the large majority of other insect clades. Lepidopteran RHG homologs, however, stand out by producing an evolutionarily derived splice isoform, identified in previous work, in addition to the newly detected hid-like isoform. Exceptional sequence diversification of select RHG homologs at the family- and genus-level explain their elusiveness in important insect genome model species like the red flour beetle Tribolium castaneum and the pea aphid Acyrthosiphon pisum. Combined, these findings expand the minimal age of the RHG gene family by about 100 million years and open new avenues for molecular cell death studies in insects.