Robert Root-Bernstein

Michigan State University | MSU · Department of Physiology

Few people exposed to human immunodeficiency virus (HIV) become infected. Among those infected, the rate of progression to full-blown acquired immunodeficiency syndrome (AIDS) and susceptibility to various opportunistic infections varies widely as does their response to antiretroviral therapies (ARTs). This review addresses these conundrums in ligh...

Recent research suggests that T-cell receptor (TCR) sequences expanded during human immunodeficiency virus and SARS-CoV-2 infections unexpectedly mimic these viruses. The hypothesis tested here is that TCR sequences expanded in patients with type 1 diabetes mellitus (T1DM) and autoimmune myocarditis (AM) mimic the infectious triggers of these disea...

A simple agent‐based model is presented that produces results matching the experimental data found by Lenski's group for ≤50,000 generations of Escherichia coli bacteria under continuous selective pressure. Although various mathematical models have been devised previously to model the Lenski data, the present model has advantages in terms of overal...

Autoimmune cardiopathies (AC) following COVID-19 and vaccination against SARS-CoV-2 occur at significant rates but are of unknown etiology. This study investigated the possible roles of viral and bacterial mimicry, as well as viral-bacterial co-infections, as possible inducers of COVID-19 AC using proteomic methods and enzyme-linked immunoadsorptio...

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammati...

What triggers type 1 diabetes mellitus (T1DM)? One common assumption is that triggers are individual microbes that mimic autoantibody targets such as insulin (INS). However, most microbes highly associated with T1DM pathogenesis, such as coxsackieviruses (COX), lack INS mimicry and have failed to induce T1DM in animal models. Using proteomic simila...

Neutrophilia and the production of neutrophil extracellular traps (NETs) are two of many measures of increased inflammation in severe COVID-19 that also accompany its autoimmune complications, including coagulopathies, myocarditis and multisystem inflammatory syndrome in children (MIS-C). This paper integrates currently disparate measures of innate...

The standard approach to exploring prebiotic chemistry is to use a small number of highly purified reactants and to attempt to optimize the conditions required to produce a particular end product. However, purified reactants do not exist in nature. We have previously proposed that what drives prebiotic evolution are complex chemical ecologies. Ther...

Published hypervariable region V-beta T cell receptor (TCR) sequences were collected from people with severe COVID-19 characterized by having various autoimmune complications, including blood coagulopathies and cardiac autoimmunity, as well as from patients diagnosed with the Kawasaki disease (KD)-like multisystem inflammatory syndrome in children...

COVID-19 patients often develop coagulopathies including microclotting, thrombotic strokes or thrombocytopenia. Autoantibodies are present against blood-related proteins including cardiolipin (CL), serum albumin (SA), platelet factor 4 (PF4), beta 2 glycoprotein 1 (β2GPI), phosphodiesterases (PDE), and coagulation factors such as Factor II, IX, X a...

Origins-of-life chemical experiments usually aim to produce specific chemical end-products such as amino acids, nucleic acids or sugars. The resulting chemical systems do not evolve or adapt because they lack natural selection processes. We have modified Miller origins-of-life apparatuses to incorporate several natural, prebiotic physicochemical se...

POLYMATHY AMONG NOBEL LAUREATES AS A CREATIVE STRATEGY—THE QUALITATIVE AND PHENOMENOLOGICAL EVIDENCE by Michele Root-Bernstein and Robert Root-Bernstein Abstract and Reprint Link: Previous statistical studies found that polymathic networks of vocational and avocational interest predominate among Nobel Prize winners, discriminating them from le...

This paper proposes the design of combination opioid–adrenergic tethered compounds to enhance efficacy and specificity, lower dosage, increase duration of activity, decrease side effects, and reduce risk of developing tolerance and/or addiction. Combinations of adrenergic and opioid drugs are sometimes used to improve analgesia, decrease opioid dos...

Pain control using opioids can be improved by combining them with adrenergic drugs in order to enhance their efficacy in a superadditive manner that retards the development of tolerance, decreases side effects, and increases their duration of action. This enhanced activity is mediated by cross-talk between adrenergic and opioid receptors involving...

Cross-talk between opioid and adrenergic receptors is well-characterized and involves second messenger systems, the formation of receptor heterodimers, and the presence of extracellular allosteric binding regions for the complementary ligand; however, the evolutionary origins of these interactions have not been investigated. We propose that opioid...

Severe COVID‐19 is often accompanied by coagulopathies such as thrombocytopenia and abnormal clotting. Rarely, such complications follow SARS‐CoV‐2 vaccination. The cause of these coagulopathies is unknown. It is hypothesized that coagulopathies accompanying SARS‐CoV‐2 infections and vaccinations result from bacterial co‐infections that synergize w...

This study examines the relationship of pneumococcal vaccination rates, influenza, measles-mumps-rubella (MMR) diphtheria-tetanus-pertussis vaccinations (DTP), polio, Haemophilus influenzae type B (Hib), and Bacillus Calmette–Guerin (tuberculosis) vaccination rates to COVID-19 case and death rates for 51 nations that have high rates of COVID-19 tes...

Severe COVID-19 is characterized by a “cytokine storm”, the mechanism of which is not yet understood. I propose that cytokine storms result from synergistic interactions among Toll-like receptors (TLR) and nucleotide-binding oligomerization domain-like receptors (NLR) due to combined infections of SARS-CoV-2 with other microbes, mainly bacterial an...

One of the ongoing challenges for gifted and talented education is that the measures used to select students for advanced educational opportunities rarely identify those most likely to make creative contributions later in life. The smartest students are rarely the most inventive. Conversely, extremely creative people are often overlooked as average...

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison o...

Two conundrums puzzle COVID‐19 investigators: 1) morbidity and mortality is rare among infants and young children and 2) rates of morbidity and mortality exhibit large variances across nations, locales, and even within cities. It is found that the higher the rate of pneumococcal vaccination in a nation (or city) the lower the COVID‐19 morbidity and...

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison o...

Abstract Background: Anosmia-hyposmia and dysgeusia are common symptoms of mild-to-moderate COVID-19 cases. They are usually, but not always, reversible and the cause is unknown. Methodology: Proteomic similarity searching (BLAST) was used to test whether SARS-CoV-2 has an unusual degree of similarity to human olfactory receptors as compared with o...

Opioids and their antagonists alter vitamin C metabolism. Morphine binds to glutathione (l-γ-glutamyl-l-cysteinyl-glycine), an intracellular ascorbic acid recycling molecule with a wide range of additional activities. The morphine metabolite morphinone reacts with glutathione to form a covalent adduct that is then excreted in urine. Morphine also b...

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison o...

A significant inverse correlation exists between rates of pneumococcal vaccination, at both national and local levels, and symptomatic cases of SARS-CoV-2 infection and death. No correlations exist to BCG, Hib, diphtheria-tetanus-pertussis, measles-mumps-rubella, or poliovirus vaccinations. This paper explored the possibility that pneumococcal vacc...

Persistent activation of toll-like receptors (TLR) and nucleotide-binding oligomerization domain-containing proteins (NOD) in the innate immune system is one necessary driver of autoimmune disease (AD), but its mechanism remains obscure. This study compares and contrasts TLR and NOD activation profiles for four AD (autoimmune myocarditis, myastheni...

Polymathy may be defined as the productive pursuit of multiple endeavors, simultaneously or serially, across a lifetime. As such, polymathic breadth of interest across knowledge domains characterizes Nobel laureates in the sciences, literature, economics, and peace, though interest patterns vary between groups. Economics laureates, like science lau...

Two conundrums have puzzled COVID-19 investigators: 1) morbidity and mortality is rare among Infants and young children and 2) rates of morbidity and mortality exhibit very large variances across nations, locals and even within cities. These differences correlate with rates of Haemophilus influenzae type B (Hib) and pneumococcal vaccination, which...

Two conundrums have puzzled COVID-19 investigators: 1) morbidity and mortality is rare among Infants and young children and 2) rates of morbidity and mortality exhibit very large variances across nations, locals and even within cities. These differences correlate with rates of Haemophilus influenzae type B (Hib) and pneumococcal vaccination, which...

Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disea...

Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disea...

Transfer factor is the name given to material derived from activated lymphocytes that is probably composed of a complex of a peptide and a short segment of RNA and which has the reported ability to transfer specific T cell immunity to uncommitted lymphocytes. Many independent groups around the world reported isolating transfer factors between 1955...

Glucotoxicity is considered to be one of the primary drivers in type 2 diabetic (T2D) pathophysiology. As such, understanding the mechanisms underlying glucotoxicity is imperative in the identification, treatment, and prevention of T2D. One contributor to glucotoxicity is protein glycation in which a reducing sugar spontaneously reacts with the ɛ‐a...

Previous studies of science, technology, engineering, mathematics, and medical (STEMM) professionals have identified a common “mental toolkit” composed of 13 “tools for thinking” that STEMM professionals use in their problem raising and problem solving. The present research surveyed a convenience sample of 225 STEMM professionals to investigate whe...

We propose that ribosomal RNA (rRNA) formed the basis of the first cellular genomes, and provide evidence from a review of relevant literature and proteonomic tests. We have proposed previously that the ribosome may represent the vestige of the first self-replicating entity in which rRNAs also functioned as genes that were transcribed into function...

On 7 May 2018, the Board on Higher Education and Workforce of the U.S. National Academies of Sciences, Engineering, and Medicine (NASEM) released a report recommending that humanities, arts, crafts, and design (HACD) practices be integrated with science, technology, engineering, mathematics, and medicine (STEMM) in college and post-graduate curricu...

Extensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and it...

The causes of insulin resistance are not well-understood in either type 1 or type 2 diabetes. Insulin (INS) is known to undergo rapid non-enzymatic covalent conjugation to glucose or other sugars (glycation). Because the insulin receptor (IR) has INS-like regions associated with both glucose and INS binding, we hypothesize that hyperglycemic condit...

Human immunodeficiency virus (HIV) hides from the immune system in part by mimicking host antigens, including human leukocyte antigens. It is demonstrated here that HIV also mimics the V-beta-D-J-beta of approximately seventy percent of about 600 randomly selected human T cell receptors (TCR). This degree of mimicry is greater than any other human...

The goal of educating for creativity must be active understanding rather than passive knowing. To understand is to have the capability to re-create, which trains the ability also to create. The ability to create requires problem-finding as well as problem-solving. It requires practice. Best practice involves the emulation of creative people and the...

Cloverleaf tRNA with a 75 nucleotide (nt) core is posited to have evolved from ligation of three 31 nt minihelices followed by symmetrical internal deletions of 9 nt within ligated acceptor stems. Statistical tests strongly support the model. Although the tRNA anticodon loop and T loop are homologs, their U-turns have been treated as distinct motif...

In contrast to theories arguing that cellular life has evolved to transmit genes, we propose instead that cellular life evolved to facilitate the full potential of self-replicating ribosomes. Our theory explicitly rejects ?master molecule? theories such as Dawkins?s ?selfish gene? in favor of the emergence of life by means of systems of increasingl...

Multiple models have been advanced for the evolution of cloverleaf tRNA. Here, the conserved archaeal tRNA core (75-nt) is posited to have evolved from ligation of 3 proto-tRNA minihelices (31-nt) and 2-symmetrical 9-nt deletions within joined acceptor stems (93-18 = 75-nt). The primary evidence for this conclusion is that the 5-nt stem 7-nt antico...

I propose a T-cell receptor (TcR)-based mechanism by which immunity mediates both “genetic self” and “microbial self” thereby, connecting microbiome disease with autoimmunity. The hypothesis is based on simple principles. First, TcR are selected to avoid strong cross-reactivity with “self,” resulting in selection for a TcR repertoire mimicking “gen...

We have proposed that the ribosome may represent a missing link between prebiotic chemistries and the first cells. One of the predictions that follows from this hypothesis, which we test here, is that ribosomal RNA (rRNA) must have encoded the proteins necessary for ribosomal function. In other words, the rRNA also functioned pre-biotically as mRNA...

The intracellular recycling of ascorbic acid from dehydroascorbic acid by the glutathione-glutathione reductase system has been well-characterized. We propose that extracellular recycling of ascorbic acid is performed in a similar manner by cysteine-rich, glutathione-like regions of the first and second extracellular loops of some aminergic recepto...

Evidence is reviewed that complementary proteins and peptides form complexes with increased antigencity and/or autoimmunogenicity. Five case studies are highlighted: 1) diphtheria toxin-antitoxin (antibody), which induces immunity to the normally non-antigenic toxin, and autoimmune neuritis; 2) tryptophan peptide of myelin basic protein and muramyl...

Studies have found little correlation between creativity and being gifted or talented, but do show that creative people are more broadly trained, have more avocational interests, and display more ability in these interests than the average person. In the sciences, technology, engineering and mathematics (STEM) fields, the avocational interests of t...

Several different classes of compounds enhance the potency of aminergic receptor ligands three-fold or more and increase their duration of activity up to ten-fold. These enhancers include the vitamins ascorbic acid and folic acid, chelators such as ethylenediaminetetraacetic acid, corticosteroids, and opioids, opiates and opiate antagonists. We hav...

Many steps in the evolution of cellular life are still mysterious. We suggest that the ribosome may represent one important missing link between compositional (or metabolism-first), RNA-world (or genes-first) and cellular (last universal common ancestor) approaches to the evolution of cells. We present evidence that the entire set of transfer RNAs...

Background: Fundamental problems faced by the protocells and their modern descendants include how to go from one phenotypic state to another; escape from a basin of attraction in the space of phenotypes; reconcile conflicting growth and survival strategies (and thereby live on 'the scales of equilibria'); and create a coherent, reproducible phenot...

Several classes of compounds that have no intrinsic activity on aminergic systems nonetheless enhance the potency of aminergic receptor ligands three-fold or more while significantly increasing their duration of activity, preventing tachyphylaxis and reversing fade. Enhancer compounds include ascorbic acid, ethylenediaminetetraacetic acid, corticos...

Rationale: Molecular mimicry theory (MMT) suggests that epitope mimicry between pathogens and human proteins can activate autoimmune disease. Group A streptococci (GAS) mimics human cardiac myosin in rheumatic heart disease (RHD) and coxsackie viruses (CX) mimic actin in autoimmune myocarditis (AM). But myosin and actin are immunologically inaccess...

Several years ago, the art historian E.M. Hafner suggested that the history of art has many similarities to the history of science. He suggested that art, like science, has paradigms that undergo revolutions. T.S. Kuhn, the historian of science who had coined the term “paradigm shift” to describe scientific revolutions, was asked to comment. His re...

Rationale: Insulin (INS) resistance associated with hyperestrogenemias occurs in gestational diabetes mellitus, polycystic ovary syndrome, ovarian hyperstimulation syndrome, estrogen therapies, metabolic syndrome, and obesity. The mechanism by which INS and estrogen interact is unknown. We hypothesize that estrogen binds directly to INS and the ins...

An effective educational framework is necessary to develop the engagement of children and adults with nature. Here we show how the tools for thinking framework can be applied to this end. The tools comprise 13 sensory- based cognitive skills that form the basis for formalized expressions of knowledge and understanding in the sciences and arts. Thes...

The possible role of infections in driving autoimmune disease (AD) has long been debated. Many theories have emerged including release of hidden antigens, epitope spread, anti-idiotypes, molecular mimicry, the adjuvant effect, antigenic complementarity, or simply that AD could be a direct consequence of activation or subversion of the immune respon...

Governments, schools, and other nonprofit organizations are engaged in critical budget decisions that may affect our economic development success. The assumption is that arts and crafts are dispensable extras. Research suggests, however, that disposing of arts and crafts may have negative consequences for the country’s ability to produce innovative...

Pfeiffer's bacillus, now known as Haemophilus influenzae (HI), was strongly implicated in the high lethality of the 1918-19 influenza pandemic. Influenza virus (IV) infection is often complicated by (HI) super-infection and certainly was so in 1918-19. We propose that the influenza pandemic of 1918-19 was caused by concurrent pandemics of IV and HI...

Our objective is to elucidate the nature of the autoimmune disregulation in diabetes through the antigen specificity of the T-cell receptor (TCR) sequences generated by patients with type 1 diabetes mellitus (T1DM). Previously we demonstrated that TCR from T1DM patients and NOD mice mimic insulin, glucagon and their receptors. We hypothesize that t...

This is the final outcome of the INBIOSA project which ends by the end of December 2011. A slighly different version including some appendices will be delivered to the EC later. We believe that this White Paper is a defining document that can be used to direct future research in Integral Biomathics. It can be the base for cooperation projects in th...

The title of this highly readable text suggests the sort of history of science that might not appeal to a working scientist or physician, and the cover illustration of Galvani and some frog legs reinforces the misimpression. Alan McComas does begin with Galvani's 18th-century discovery that electricity could make a dead frog's leg jump, but that is...