Pre-existing medical conditions and co-infections are common to all human populations, although the natures of the pre-existing conditions and the types of co-infections vary. For these reasons, among others, the arrival of a highly infectious pathogenic agent may differentially affect the disease burden in different sub-populations, as a function of varying combinations of endemic disease, chronic disease, genetic or epigenetic vulnerabilities, compromised immunological status, and socially determined risk exposure. The disease burden may also vary considerably by age cohort and (...) socio-economic status. The social consequences of infection, the medical sequelae, and the paths of recovery from infection may also vary, according to these variables. As a result, different sub-populations may have different experiences of a disease process, including when and how an epidemic comes to an end. This essay suggests that historians' engagement with path-breaking biological and medical anthropological research will allow new approaches to understanding disease processes that will enrich the study of epidemics and their endings. It is organized in three sections. The first discusses some general approaches to and assumptions about epidemics that are used by many historians. The second introduces new perspectives on the study of historical epidemics opened up by the medical anthropological concept of syndemic disease interactions and by an engagement with biological scientific perspectives. It briefly discusses two rural epidemics-one of anemia caused by the syndemic interaction of hookworm and malaria co-infections in early 20th-century British Malaya, and the other of rebound infections caused by the loss of acquired immunity to falciparum malaria in mid-20th-century Liberia-that illustrate, respectively, the utility of the concept of syndemic disease interactions and the centrality of immunological status in understanding epidemic outbreaks in these discrete populations. The third section addresses some of the research considerations involved in moving beyond the single pathogen model of epidemic disease. (shrink)

본 연구의 목표는 “도덕의 병원적 속성”에 대한 프로이트의 정의 및 대안을 비판적으로 분석하면서, 도덕으로 인해서 발생한 정신적 고통, 소위 도덕적 질병을 치유하기 위한 하나의 대안으로서 구조구성주의 상담모델을 구성하는 것이다. 이를 위해 필자는 일차적으로 니체, 프로이트 그리고 라캉으로 이어지는 윤리에 대한 비합리론적 이론과 플라톤, 칸트, 하버마스 그리고 매킨타이어로 이어지는 윤리에 대한 합리론적 이론 사이의 논쟁을 비판적으로 분석하고 이들을 “구조구성주의의 윤리설”(필자의 고유한 명칭)로 종합하는 것이고, 이차적으로 이를 근거로 한편에서는 정신분석적 상담모형과 인지행동치료 상담모형을 종합하고, 다른 한편으로는 베이지언 인지모형(Bayesian Cognition Model)과 크래이그의 수사학적 (...) 소통모형(Rhetorical Model of communication by Craig, R. T.)을 통합하는 새로운 상담모형, 즉 “구조구성주의 상담모형”(필자의 교유한 명칭)을 구성하고자 한다. 그러나 현재의 제한적인 이 지면에서 상기의 모든 내용을 다루는 것은 불가능하다. 이에 현재의 논문에서는 우선 일차적인 문제, 즉 윤리에 대한 합리론적 입장과 이것에 대한 비판인 정신분석적 입장을 비교하면서, 양자의 종합 가능성 및 그 필연성을 구조구성주의 윤리설이라는 이름으로 해명하는 데 집중할 것이다. 그리고 이를 근거로 구조구성주의 상담모델을 구성하는 작업은 차후에 다른 지면에서 수행될 것이다. (shrink)

COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover the evolutionary dispositions involved (...) in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed. (shrink)

Modelling contagious diseases needs to include a mechanistic knowledge about contacts between hosts and pathogens as specific as possible, e.g., by incorporating in the model information about social networks through which the disease spreads. The unknown part concerning the contact mechanism can be modelled using a stochastic approach. For that purpose, we revisit SIR models by introducing first a microscopic stochastic version of the contacts between individuals of different populations (namely Susceptible, Infective and Recovering), then by adding a random (...) perturbation in the vicinity of the endemic fixed point of the SIR model and eventually by introducing the definition of various types of random social networks. We propose as example of application to contagious diseases the HIV, and we show that a micro-simulation of individual based modelling (IBM) type can reproduce the current stable incidence of the HIV epidemic in a population of HIV-positive men having sex with men (MSM). (shrink)

In this paper, my aim is to understand the origin of experimental and scientific models of pathogeny of the diseases of the nervous system in the Salpêtrière (Paris). I will analyse the role of the contexts of cell theory, microscopy and the advances in histological techniques in the creation of various pathogenic models, based on the concept of the cell, the Wallerian degeneration and the neurone concept. I argue that, as medicine and pathology remain autonomous in their methods and (...) goals, because of the evident degree of complexity of diseases, close and reciprocal interactions with sciences, their practices and theories, make it possible to establish convergences between clinical observations, pathological data and those from the experimental models of pathologies. The search for pathogenic models behaves like an engine, which is efficient in assembling facts, in testing pathogeneses and reforming nosologies, combined with the breakthroughs in biology. This paper is a case study showing the emergence of such interactions in the last decades of the nineteenth-century in Paris. (shrink)

This aricle discusses the similarity between the propagation of pathogens (viruses and worms) on computer networks and the proliferation of pathogens in cellular organisms (organisms with genetic material contained within a membrane-encased nucleus). It introduces several biological mechanisms which are used in these organisms to protect against such pathogens and presents security models for networked computers inspired by several biological paradigms, including genomics (RNA interference), proteomics (pathway mapping), and physiology (immune system). In addition, the study of epidemiological models for disease (...) control can inspire methods for controlling the spread of pathogens across multiple nodes of a network. It also presents results based on the authors’ research in immune system modeling. (shrink)

Humans accumulate porphyrins in the body mostly during the course of porphyrias, diseases caused by defects in the enzymes of the heme biosynthesis pathway and that produce acute attacks, skin lesions and liver cancer. In contrast, some wild mammals and birds are adapted to accumulate porphyrins without injurious consequences. Here we propose viewing such physiological adaptations as potential solutions to human porphyrias, and suggest certain wild animals as models. Given the enzymatic activity and/or the patterns of porphyrin excretion and accumulation, (...) the fox squirrel, the great bustard and the Eurasian eagle owl may constitute overlooked models for different porphyrias. The Harderian gland of rodents, where large amounts of porphyrins are synthesized, presents an underexplored potential for understanding the carcinogenic/toxic effect of porphyrin accumulation. Investigating how these animals avoid porphyrin pathogenicity may complement the use of laboratory models for porphyrias and provide new insights into the treatment of these disorders. (shrink)

We discuss potential biorisks from large language models (LLMs). AI assistants based on LLMs such as ChatGPT have been shown to significantly reduce barriers to entry for actors wishing to synthesize dangerous, potentially novel pathogens and chemical weapons. The harms from deploying such bioagents could be further magnified by AI-assisted misinformation. We endorse several policy responses to these dangers, including prerelease evaluations of biomedical AIs by subject-matter experts, enhanced surveillance and lab screening procedures, restrictions on AI training data, and access (...) controls on biomedical AI. We conclude with a suggestion about future research directions in bioethics. (shrink)

We analyse the effect of the regulatory T cells (Tregs) in the local control of the immune responses by T cells. We obtain an explicit formula for the level of antigenic stimulation of T cells as a function of the concentration of T cells and the parameters of the model. The relation between the concentration of the T cells and the antigenic stimulation of T cells is an hysteresis, that is unfold for some parameter values. We study the appearance (...) of autoimmunity from cross-reactivity between a pathogen and a self antigen or from bystander proliferation. We also study an asymmetry in the death rates. With this asymmetry we show that the antigenic stimulation of the Tregs is able to control locally the population size of Tregs. Other effects of this asymmetry are a faster immune response and an improvement in the simulations of the bystander proliferation. The rate of variation of the levels of antigenic stimulation determines if the outcome is an immune response or if Tregs are able to maintain control due to the presence of a transcritical bifurcation for some tuning between the antigenic stimuli of T cells and Tregs. This behavior is explained by the presence of a transcritical bifurcation. (shrink)

Fincher & Thornhill's (F&T's) model is not entirely supported by common patterns of affect behaviors among people who live under varying climatic conditions and among people who endorse varying levels of (Western) religiosity and conservative political ideals. The authors' model is also unable to account for intra-regional heterogeneity in assortative sociality, which, we argue, can be better explained by a framework that emphasizes the differential expression of fundamental social cues for maintaining distinct social network structures.

In the atavistic model of cancer progression, tumor cell dedifferentiation is interpreted as a reversion to phylogenetically earlier capabilities. The more recently evolved capabilities are compromised first during cancer progression. This suggests a therapeutic strategy for targeting cancer: design challenges to cancer that can only be met by the recently evolved capabilities no longer functional in cancer cells. We describe several examples of this target‐the‐weakness strategy. Our most detailed example involves the immune system. The absence of adaptive immunity in (...) immunosuppressed tumor environments is an irreversible weakness of cancer that can be exploited by creating a challenge that only the presence of adaptive immunity can meet. This leaves tumor cells more vulnerable than healthy tissue to pathogenic attack. Such a target‐the‐weakness therapeutic strategy has broad applications, and contrasts with current therapies that target the main strength of cancer: cell proliferation. (shrink)

Many of the most virulent and problematic eukaryotic pathogens have evolved from photosynthetic ancestors, such as apicomplexans, which are responsible for a wide range of diseases including malaria and toxoplasmosis. The primary barrier to understanding the early stages of evolution of these parasites has been the difficulty in finding parasites with closely related free‐living lineages with which to make comparisons. Parasites found throughout the florideophyte red algal lineage, however, provide a unique and powerful model to investigate the genetic origins (...) of a parasitic lifestyle. This is because they share a recent common ancestor with an extant free‐living red algal species and parasitism has independently arisen over 100 times within this group. Here, we synthesize the relevant hypotheses with respect to how these parasites have proliferated. We also place red algal research in the context of recent developments in understanding the genome evolution of other eukaryotic photosynthesizers turned parasites. (shrink)

Doctors have always thought, it seems, that the female body is more susceptible to illness than the male. Ancient medicine founded this dogma on the doctrine of elementary qualities, in attributing to woman a cold and humid constitution. As heat is the principal instrument which nature uses to produce the forces of the body and to maintain them, it must be lacking in woman, as is proved by her weakness, the softness of her limbs, her lack of external sexual organs (...) and the crudeness of her menstrual blood. If the Aristotelians and the Galenists diverge, in the Renaissance and in the XVIIth century, about the nature—fertile or not—of the “female seed,” they agree to pledge the female body to illnesses. Such a predisposition is explained by the female constitution: its coldness and its humidity, as well as retaining women's strength badly, contribute to giving them a “soft, slack body, of rare texture,” little suited to letting the body fluids, of which it is full, circulate correctly; their blood, corrupted by humidity, instead of being properly heated like it is in men, accumulates, blocks up the too small blood-vessels and causes all the illnesses of which they are the habitual victims. To this it is necessary to add the pathogenic importance of the womb, “a part of the body so sensitive and so easily upset, that its least indisposition causes an infinity of strange and almost unbearable evils.” The indispositions which affect this part of the body are always in relation to humidity or dryness, that is with “the two excrements” which it receives: sperm and menstrual blood. Whether, insufficiently impregnated by the virile liquor, “it mounts to the liver and other higher parts of the body to suck humidity from them until it becomes moist,” or it retains for an abnormally long time the seed, which decays inside it; or the periods are suppressed, or on the other hand they are produced too often; all womens illnesses are a question of impeded or excessive discharge. (shrink)

Insight into animal biology and development provided by classical genetic analysis of the model organism Drosophila melanogaster was an incentive to develop advanced genetic tools for this insect. But genetic systems for the over one million other known insect species are largely undeveloped. With increasing information about insect genomes resulting from next generation sequencing, RNA interference is now the method of choice for reverse genetics, although it is constrained by the means of delivery of interfering RNA. A recent advance (...) to ensure sustained delivery with minimal experimental intervention or trauma to the insect is to exploit commensal bacteria for symbiont‐mediated RNA interference. This technology not only offers an efficient means for RNA interference in insects in laboratory conditions, but also has potential for use in the control of human disease vectors, agricultural pests and pathogens of beneficial insects. (shrink)

Qualitative validation consists in showing that a model is able to mimic available observed data. In population level biological models, the available data frequently represent a group status, such as pool testing, rather than the individual statuses. They are aggregated. Our objective was to explore an approach for qualitative validation of a model with aggregated data and to apply it to validate a stochastic model simulating the bovine viral-diarrhoea virus (BVDV) spread within a dairy cattle herd. Repeated (...) measures of the level of BVDV-specific antibodies in the bulk-tank milk (total milk production of a herd) were used to summarise the BVDV herd status. First, a domain of validation was defined to ensure a comparison restricted to dynamics of pathogen spread well identified among observed aggregated data (new herd infection with a wide BVDV spread). For simulations, scenarios were defined and simulation outputs at the individual animal level were aggregated at the herd level using an aggregation function. Comparison was done only for observed data and simulated aggregated outputs that were in the domain of validation. The validity of our BVDV model was not rejected. Drawbacks and ways of improvement of the approach are discussed. (shrink)

The data analyzed in this paper are part of the results described in Bueno et al. (2000). Three cytogenetics endpoints were analyzed in three populations of a species of wild rodent – Akodon montensis – living in an industrial, an agricultural, and a preservation area at the Itajaí Valley, State of Santa Catarina, Brazil. The polychromatic/normochromatic ratio, the mitotic index, and the frequency of micronucleated polychromatic erythrocites were used in an attempt to establish a genotoxic profile of each area. It (...) was assumed that the three populations were in the same conditions with respect to the influence of confounding factors such as animal age, health, nutrition status, presence of pathogens, and intra- and inter-populational genetic variability. Therefore, any differences found in the endpoints analyzed could be attributed to the external agents present in each area. The statistical models used in this paper are mixtures of negative-binomials and Poisson variables. The Poisson variables are used as approximations of binomials for rare events. The mixing distributions are beta densities. The statistical analyzes are under the bayesian perspective, as opposed to the frequentist ones often considered in the literature, as for instance in Bueno et al. (2000). (shrink)

A class of maize mutants, collectively known as disease lesion mimics, display discrete disease‐like symptoms in the absence of pathogens. It is intriguing that a majority of these lesion mimics behave as dominant gain‐of‐function mutations. The production of lesions is strongly influenced by light, temperature, developmental state and genetic background. Presently, the biological significance of this lesion mimicry is not clear, although suggestions have been made that they may represent defects in the plants' recognition of, or response to, pathogens. One (...) feature that is common to all lesion mimics is their association with cell death. In plants, as in animals, a number of developmental and pathological processes exist where controlled cell death, whether programmed or triggered in response to physiological or environmental stimuli, constitutes the normal aspect of life. Might disease lesion mimic mutations represent variants where regulation of desirable cell death has gone awry? In this paper we argue that this might be the case, and further conjecture that these mutants offer a unique opportunity for studying the genetic and cellular mechanisms of cell death in plants. (shrink)

With the ever‐increasing lifespan along with societal changes, women can marry and procreate later than in previous centuries. However, pathogenic genetic variants segregating in the population can lead to female subfertility or infertility well before the average age of normal menopause, leading to counter‐selection of such deleterious alleles. In reviewing this field, we speculate that a logical consequence would be the later occurrence of menopause and the extension of women's reproductive lifespan. We illustrate this point with a simple (...) class='Hi'>model that applies to other variants that contribute to female infertility, including epigenetic variation. We also consider the effect of medical interventions and lifestyle. (shrink)

berkley's pathogen model of sex differences in pain is inconsistent with women outliving men by several years. The vagina is far more resistant to pathogens than is the rectum. Vaginal stimulation produces intense analgesia in rats and humans. Possible evolutionary and cardiovascular factors are also noted.

Recently, we found that the Pseudomonas aeruginosa type II secreted protease IV functions as a unique Arabidopsis innate immunity elicitor. The protease IV‐activated pathway involves G protein signaling and raises the question of how protease elicitation leads to the activation of G protein‐mediated signaling, because plants do not appear to have metazoan‐like G protein‐coupled receptors. Importantly, our data suggest that Arabidopsis has evolved a mechanism to detect the proteolytic activity of a pathogen‐encoded protease, supporting the host‐pathogen arms race model. (...) In the case of opportunistic multi‐host pathogens like P. aeruginosa, however, it is not plausible that P. aeruginosa is simultaneously co‐evolving in a gene‐for‐gene manner with all of its potential hosts, which include plants, nematodes, insects, and mammals. This prompts us to ask what is the driving force for co‐evolution of defense response in Arabidopsis and pathogenesis of P. aeruginosa, which might not have been subject to iterative cycles of evolutionary selections. (shrink)

The human pathogen Vibrio cholerae exhibits two distinct lifestyles: one in the aquatic environment where it often associates with chitinous surfaces and the other as the causative agent of the disease cholera. While much of the research on V. cholerae has focused on the host‐pathogen interaction, knowledge about the environmental lifestyle of the pathogen remains limited. We recently showed that the polymer chitin, which is extremely abundant in aquatic environments, induces natural competence as a mode of horizontal gene transfer and (...) that this competence regulon also includes the type VI secretion system (T6SS), a molecular killing device. Here, I discuss the putative consequences that chitin‐induced T6SS activation could have on intestinal colonization and how the transmission route might influence disease outcome. Moreover, I propose that common infant animal models for cholera might not sufficiently take into account T6SS‐mediated interbacterial warfare between V. cholerae and the intestinal microbiota. (shrink)

A pathogenic connection between autoreactive T cells, fungal infection, and carcinogenesis has been demonstrated in studies of human autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy as well as in a mouse model in which kinase-dead Ikkα knock-in mice develop impaired central tolerance, autoreactive T cell–mediated autoimmunity, chronic fungal infection, and esophageal squamous cell carcinoma, which recapitulates APECED. IκB kinase α is one subunit of the IKK complex required for NF-κB activation. IKK/NF-κB is essential for central tolerance establishment by regulating the development of (...) medullary thymic epithelial cells that facilitate the deletion of autoreactive T cells in the thymus. In this review, we extensively discuss the pathogenic roles of inborn errors in the IKK/NF-κB loci in the phenotypically related diseases APECED, immune deficiency syndrome, and severe combined immunodeficiency; differentiate how IKK/NF-κB components, through mTEC, T cells/leukocytes, or epithelial cells, contribute to the pathogenesis of infectious diseases, autoimmunity, and cancer; and highlight the medical significance of IKK/NF-κB in these diseases. IKK/NF-κB regulates the expression of many genes that encode proteins involved in many crucial biological functions, such as immunity, tissue homeostasis, and fungal/bacterial/viral infections. Also, IKKα plays anti-tumor activities in many organs independently of NF-κB pathways. Thus, an inborn error in one of these gene loci can cause severe human diseases through these complicated mechanisms. (shrink)

To enable microbial colonisation of the gut mucosa, the intestinal immune system must not only react to danger signals but also recognize cues that indicate safety. Safety recognition, paradoxically, is mediated by the same environmental sensors that are involved in signalling danger. Indeed, in addition to their well established role in inducing inflammation in response to stress signals, pattern recognition receptors (PRRs) and a variety of metabolic sensors also promote gut-microbiota symbiosis by responding to "microbial symbiosis factors", "resolution-associated molecular patterns", (...) markers of energy extraction and other signals indicating the absence of pathogenic infection and tissue damage. Here we focus on how the paradoxical role of immune receptors and other environmental sensors define the microbiota signature of the individual. (shrink)

The strategic pluralism model depends upon pathogen prevalence and environmental hardship being independent. Evidence is presented that they are positively correlated. The rise in short-term mating strategy in the United States is better explained by changes in the operational sex ratio than by increases in pathogen prevalence. Nonetheless, in highlighting the advantages of a high-investment strategy to less attractive males, Gangestad & Simpson's model helps to clarify the dynamics of frequency-dependent selection.

Recent evidence indicates that inhibition of protein translation may be a common pathogenic mechanism for peripheral neuropathy associated with mutant tRNA synthetases (aaRSs). aaRSs are enzymes that ligate amino acids to their cognate tRNA, thus catalyzing the first step of translation. Dominant mutations in five distinct aaRSs cause Charcot‐Marie‐Tooth (CMT) peripheral neuropathy, characterized by length‐dependent degeneration of peripheral motor and sensory axons. Surprisingly, loss of aminoacylation activity is not required for mutant aaRSs to cause CMT. Rather, at least for (...) some mutations, a toxic‐gain‐of‐function mechanism underlies CMT‐aaRS. Interestingly, several mutations in two distinct aaRSs were recently shown to inhibit global protein translation in Drosophila models of CMT‐aaRS, by a mechanism independent of aminoacylation, suggesting inhibition of translation as a common pathogenic mechanism. Future research aimed at elucidating the molecular mechanisms underlying the translation defect induced by CMT‐mutant aaRSs should provide novel insight into the molecular pathogenesis of these incurable diseases. (shrink)

Scientific reasoning represents complex argumentation patterns that eventually lead to scientific discoveries. Social epistemology of science provides a perspective on the scientific community as a whole and on its collective knowledge acquisition. Different techniques have been employed with the goal of maximization of scientific knowledge on the group level. These techniques include formal models and computer simulations of scientific reasoning and interaction. Still, these models have tested mainly abstract hypothetical scenarios. The present thesis instead presents data-driven approaches in social epistemology (...) of science. A data-driven approach requires data collection and curation for its further usage, which can include creating empirically calibrated models and simulations of scientific inquiry, performing statistical analyses, or employing data- mining techniques and other procedures. -/- We present and analyze in detail three co-authored research projects on which the thesis’ author was engaged during her PhD. The first project sought to identify optimal team composition in high energy physics laboratories using data-mining techniques. The results of this project are published in (Perović et al. 2016), and indicate that projects with smaller numbers of teams and team members outperform bigger ones. In the second project, we attempted to determine whether there is an epistemic saturation point in experimentation in high energy physics. The initial results from this project are published in (Sikimić et al. 2018). In the thesis, we expand on this topic by using computer simulations to test for biases that could induce scientists to invest in projects beyond their epistemic saturation point. Finally, in previous examples of data-driven analyses, citations are used as a measure of epistemic efficiency of projects in high energy physics. In order to additionally justify and analyze the usage of this parameter in their data-driven research, in the third project Perović & Sikimić (2019) analyzed and compared inductive patterns in experimental physics and biology with the reliability of citation records in these fields. They conclude that while citations are a relatively reliable measure of efficiency in high energy physics research, the same does not hold for the majority of research in experimental biology. -/- Additionally, contributions of the author that are for the first time published in this theses are: (a) an empirically calibrated model of scientific interaction of research groups in biology, (b) a case study of irregular argumentation patterns in some pathogen discoveries, and (c) an introductory discussion of the benefits and limitations of data- driven approaches to the social epistemology of science. Using computer simulations of an empirically calibrated model, we demonstrate that having several levels of hierarchy and division into smaller research sub-teams is epistemically beneficial for researchers in experimental biology. We also show that argumentation analysis in biology represents a good starting point for further data-driven analyses in the field. Finally, we conclude that a data-driven approach is informative and useful for science policy, but requires careful considerations about data collection, curation, and interpretation. (shrink)

The guard-guardee model for plant immunity describes how resistance proteins in host cells monitor host target proteins that are manipulated by pathogen effector proteins. A recently suggested extension of this model includes decoys, which are duplicated copies of guardee proteins, and have the sole function to attract the effector and, when modified by the effector, trigger the plant immune response. Here we present a proof-of-principle model for the functioning of decoys in plant immunity, quantitatively developing this experimentally (...) derived concept. Our model links the basic cellular chemistry to the outcomes of pathogen infection and resulting fitness costs for the host. In particular, the model allows identification of conditions under which it is optimal for decoys to act as triggers for the plant immune response, and of conditions under which it is optimal for decoys to act as sinks that bind the pathogen effectors but do not trigger an immune response. (shrink)

Since the 1930s, scientists studying the neurological disease scrapie had assumed that the infectious agent was a virus. By the mid 1960s, however, several unconventional properties had arisen that were difficult to reconcile with the standard viral model. Evidence for nucleic acid within the pathogen was lacking, and some researchers considered the possibility that the infectious agent consisted solely of protein. In 1982, Stanley Prusiner coined the term `prion' to emphasize the agent's proteinaceous nature. This infectious protein hypothesis was (...) denounced by many scientists as `heretical'.This two-part essay asks why the concept of an infectious protein was considered controversial. Some biologists justified their evaluation of this hypothesis on the grounds that an infectious protein contradicted the `central dogma of molecular biology'. Others referred to vague theoretical constraints such as molecular biology's `theoretical structure' or `framework'. Examination of the objections raised by researchers reveals exactly what generalizations were being challenged by a protein model of infection.This two-part survey of scrapie and prion research reaches several conclusions: A theoretical framework is present in molecular biology, exerting its influence in hypothesis formation and evaluation; This framework consists of several related, yet separable, generalizations or `elements', including Francis Crick's Central Dogma and Sequence Hypothesis, plus notions concerning infection, replication, protein synthesis, and protein folding; The term `central dogma' has stretched beyond Crick's original 1958 definition to encompass at least two other `framework elements': replication and protein synthesis; and From the study of scrapie and related diseases, biological information has been delineated into at least two classes: sequential and what I call `conformational'.In Part I of this essay, a brief review of the central dogma was given, and the developments in scrapie research from 1965 to 1972 were traced. This section summarized many of the puzzling, non-virus-like properties of the scrapie agent. Alternative hypotheses to the viral explanation were presented, including early versions of a protein-only hypothesis. Part II of this essay will follow the developments in scrapie and prion research from the mid-1970s through 1991. The growing prominence of a protein-only model of infection will be countered by continued objections from many researchers to a pathogen devoid of nucleic acid. These objections will help illuminate those generalizations in molecular biology that were indeed challenged by a protein-only model of infection. (shrink)

AbstractDuring the Covid-19 pandemic, ethicists and researchers proposed human challenge studies as a way to speed development of a vaccine that could prevent disease and end the global public health crisis. The risks to healthy volunteers of being deliberately infected with a deadly and novel pathogen were not low, but the benefits could have been immense. This essay is a history of the three major efforts to set up a challenge model and run challenge studies in 2020 and 2021. (...) The pharmaceutical company Johnson and Johnson, the National Institutes of Health in the United States, and a private-public partnership of industry, university, and government partners in Britain all undertook preparations. The United Kingdom’s consortium began their Human Challenge Programme in March of 2021.Beyond documenting each effort, the essay puts these scientific and ethical debates in dialogue with the social, epidemiological, and institutional conditions of the pandemic as well as the commercial, intellectual, and political systems in which medical research and Covid-19 challenge studies operated. It shows how different institutions understood risk, benefit, and social value depending on their specific contexts. Ultimately the example of Covid-19 challenge studies highlights the constructedness of such assessments and reveals the utility of deconstructing them retrospectively so as to better understand the interplay of medical research and research ethics with larger social systems and historical contexts. (shrink)

Emerging evidence supports the role for the intracellular domains of amyloid precursor protein (APP) in the physiology and function of APP. In this short report, I discuss the hypothesis that mutation of Tyr682 on the Y682ENPTY687 C‐terminal motif of APP may be directly or indirectly associated with alterations in APP functioning and activity, leading to neuronal defects and deficits. Mutation of Tyr682 induces an early and progressive age‐dependent cognitive and locomotor decline that is associated with a loss of synaptic connections, (...) a decrease in cholinergic tone, and defects in NGF signaling. These findings support a model in which APP‐C‐terminal domain exerts a pathogenic function in neuronal development and decline, and suggest that Tyr682 potentially could modulate the properties of APP metabolites in humans. (shrink)

Genetic and environmental factors leading to Alzheimer's disease (AD) converge in a pathogenic pathway that leads to the accumulation of mis‐folded amyloid peptide (Aβ) in the brain. Removal of Aβ from the brain has thus been the focus of academic and industrial research in the last decade. The concept of immunization therapy could be proven in animal models mimicking amyloid pathology but a multicenter clinical trial in which AD patients were vaccinated with aggregated Aβ has resulted in somewhat unanticipated (...) and partially conflicting results. The occurrence of meningoencephalitis in 6% of vaccinated individuals forced the discontinuation of the clinical study, preventing the generation of sufficient data for an unequivocal statement about the effectiveness of such a therapy approach. This study, however, clearly showed that vaccination induced the production of antibodies against Aβ in some immunized patients. Moreover, circulating anti‐Aβ antibodies are found in healthy humans suggesting a protective role of such physiological antibodies. Nonetheless, the physiological role of the immune system in preventing AD is not fully understood. This article summarizes crucial animal and clinical data underscoring the potential of the immune system for AD treatment. BioEssays 29:927–932, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

There is a steadily growing literature on the role of the immune system in psychiatric disorders. So far, these advances have largely taken the form of correlations between specific aspects of inflammation (e.g. blood plasma levels of inflammatory markers, genetic mutations in immune pathways, viral or bacterial infection) with the development of neuropsychiatric conditions such as autism, bipolar disorder, schizophrenia and depression. A fundamental question remains open: why are psychiatric disorders and immune responses intertwined? To address this would require a (...) step back from a historical mind–body dualism that has created such a dichotomy. We propose three contributions of active inference when addressing this question: translation, unification, and simulation. To illustrate these contributions, we consider the following questions. Is there an immunological analogue of sensory attenuation? Is there a common generative model that the brain and immune system jointly optimise? Can the immune response and psychiatric illness both be explained in terms of self-organising systems responding to threatening stimuli in their external environment, whether those stimuli happen to be pathogens, predators, or people? Does false inference at an immunological level alter the message passing at a psychological level (or vice versa) through a principled exchange between the two systems? (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Post-Traumatic Hermeneutics: Melancholia in the Wake of TraumaAngelika Rauch (bio)1Classical Analysis: Problems for Trauma TherapyAccording to the Journal of the American Psychoanalytical Association, American ego psychology has taken a leading role in debunking what it considers antiquated Freudian approaches to the study of trauma. As neutral observers and students of the facts, ego psychologists have purportedly reclaimed the study of trauma as the search for an objectifiable traumatic event (...) in the past, one that can be accessed as recovered memory, as a specimen of pathogenic development, or as cognitive and behavioral effects that point to an inaccessible implied memory buried in the psyche. Central to this revision of psychoanalytical trauma therapy is the dismissal of Nachträglichkeit as an antiquated and irrelevant concept. Harold P. Blum, for instance, writes in a recent article of JAPA that “‘deferred action’ is an ambiguous concept, a dubious, antiquated, theoretical legacy.” According to Blum, “deferred action overlooks the immediate and potentially powerful effects of preoedipal trauma and is dissociated from considerations of cumulative trauma and developmental disturbance.” [1155]. With respect to Freud’s case of the Wolf-Man, Blum states that “[d]eferred action emphasized traumatic events and memory rather than cumulative developmental effects of shock and strain trauma, and pathogenic object relationships.” Key to Blum’s view, then, is the assertion that “the concept of deferred action deterred consideration of real infantile experience and the complex overdetermination of pathogenesis through development” [1156]. Blum apparently takes the side of those who like to argue that trauma is more real than imagined. Whereas oedipal trauma is an imaginary or illusory trauma, preoedipal trauma is comprehensible as real shock and, as such, is empirically true. This is an idea that is very compatible with “recovered memory” therapy, a subject that has become controversial in recent debates about child abuse and recovered memory syndrome.In contrast, Arnold H. Modell in Other Times, Other Realities points out that “[t]he concept of Nachträglichkeit is virtually unknown among American psychoanalysts. This may be due in part to Strachey’s faulty translation; but this idea is also inconsistent with the belief in an orderly hierarchical psychic development such as that envisioned by ego psychologists.” [3]. In other words, Freudian Nachträglichkeit violates the principles of space and time assumed by empirical scientists whose conceptions are founded on the causality of such principles as stimulus/response. It is here, of course, that ego psychology’s treatment of trauma would come into conflict not only with Freudian analysis, including its French Freudian variants, but with the kind of trauma studies being conducted by the contributors to Cathy Caruth’s Trauma: Explorations in Memory. They include Bessel [End Page 111] van der Kolk, Onno van der Hart, Shoshana Felman, Dori Laub, Robert Lifton, and, of course, Cathy Caruth herself.Emphasis on the reality of traumatic shock (as abuse, stress, accident, and so on), however important it may be, loses sight of a hermeneutical dimension of psychoanalytic therapy that Caruth and her contributors emphasize: the question of how meanings are associated or bound to the understanding of life’s events. My own clinical approach to psychoanalysis favors the introduction of an even stronger hermeneutical perspective that is sensitive to the kinds of issues raised by philosophers like Dilthey, Heidegger, Benjamin, and Gadamer, for whom the question of experience is not reducible to restricted understandings of stimulus/response, nor—as in the case of Caruth (for example, in Unclaimed Experience)—to the privileging of language as a formal (that is, literary) construct. Rather, I am interested in emphasizing a hermeneutics of the therapeutic encounter within which questions of language, culture, history, and behavior are situated. With respect to trauma therapy, I will introduce a number of well-known analytical contributions even as I take the following statement of Arnold Modell’s as my point of departure:The analyst or therapist becomes an unwitting collaborator in the recreation of the past, while still retaining a proximity to present time. The therapist becomes the person with whom one can reexperience trauma within a new context or experience for the first time what has been absent in the past. Affects belonging to... (shrink)

Alzheimer's disease (AD) is the most common cause of dementia, and there is currently no cure. The “β‐amyloid cascade hypothesis” of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three‐dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology (...) including β‐amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery. (shrink)

Abstractc‐Rel is a proto‐oncogene first identified as the cellular counterpart of the v‐Rel oncogene derived from the avian reticuloendotheliosis retrovirus (REV‐T). It was subsequently discovered that c‐Rel belongs to the NF‐κB/Rel transcription factor family whose members share a common DNA recognition motif and similar signaling pathways. Despite the similarities, however, each NF‐κB/Rel member possesses unique properties with regard to tissue expression pattern, response to receptor signals and target gene specificity. These differences are fairly evident from the non‐redundant phenotypes exhibited by (...) individual NF‐κB/Rel knockout mice. Hence the work described in this review will compare and contrast the various physiological functions of c‐Rel to those of other NF‐κB members, particularly with respect to the regulation of proliferation, survival and effector functions in multiple hematopoietic and immunological cell types. The study of c‐Rel knockout mice in several disease models will also be discussed as they reveal an important role for c‐Rel in response to allergens, auto‐antigens, allo‐antigens and pathogenic infection. BioEssays 25:767–780, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Understanding how complex sexual reproduction arose, and why sexual organisms have been more successful than otherwise similar asexual organisms, is a longstanding problem in evolutionary biology. Within this problem, the potential role of endosymbionts or intracellular pathogens in mediating primitive genetic transfers is a continuing theme. In recent years, several remarkable activities of mitochondria have been observed in the germline cells of complex eukaryotes, and it has been found that bacterial endosymbionts related to mitochondria are capable of manipulating diverse aspects (...) of metazoan gametogenesis. An attempt is made here to rationalize these observations with an endosymbiotic model for the evolutionary origins of sex. It is hypothesized that the contemporary life cycle of germline cells has descended from the life cycle of the endosymbiotic ancestor of the mitochondrion. Through an actin‐based motility that drove it from one cell to another, the rickettsial ancestor of mitochondria may have functioned as a primitive transducing particle, the evolutionary progenitor of sperm. BioEssays 26:558–566, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Activating the ERK pathway (extracellular signal‐regulated kinase pathway) has proven beneficial in several models of Huntington's disease (HD), and drugs that are protective in HD models have recently been found to activate ERK. Thus, the ERK cascade may be a potential target for therapeutic intervention in this currently untreatable disorder. HD is caused by an expanded polyglutamine repeat in the huntingtin (Htt) protein that actuates a diverse set of pathogenic mechanisms. In response to mutant Htt, ERK is activated and (...) directs a protective transcriptional response and inhibits caspase activation. Paradoxically, Htt also interferes with several signaling events of the ERK pathway. Mutant Htt compromises the ERK‐dependent transcriptional response to corticostriatal BDNF signaling. Mutant Htt also hinders glutamate uptake from the synaptic cleft by down‐regulating ERK‐dependent expression of glutamate transporters, leaving cells vulnerable to excitotoxicity. Some of this cellular complexity can be capitalized on to achieve selective activation of ERK, which can be protective. (shrink)

Over 20 unstable microsatellite repeats have been identified as the cause of neurological disease in humans. The repeat nucleotide sequences, their location within the genes, the ranges of normal and disease‐causing repeat length and the clinical outcomes differ. Unstable repeats can be located in the coding or the non‐coding region of a gene. Different pathogenic mechanisms that are hypothesised to underlie the diseases are discussed. Evidence is given both from studies in simple model systems and from studies on (...) human material and in animal models. Since somatic instability might affect the clinical outcome, this is briefly touched on. Available data and theories on the timing and mechanisms of the repeat instability itself are discussed, along with factors that have been observed to affect instability. Finally, the question of why the often harmful unstable repeats have been maintained throughout evolution is addressed. (shrink)

While a number of valid molecular targets have been discovered for tumours over the past decade, finding an effective way of delivering therapeutic genes specifically to tumours has proved more problematic. A variety of viral and non‐viral delivery vehicles have been developed and applied in anti‐cancer gene therapies. However, these suffer from either inefficient and/or short‐lived gene transfer to target cells, instability in the bloodstream and inadequate tumour targeting. Recently, various types of non‐pathogenic obligate anaerobic and facultative anaerobic bacteria (...) have been shown to infiltrate and selectively replicate within solid tumours when delivered systemically. This has prompted the development of cancer gene therapy protocols that use such bacteria as gene delivery vehicles. Here, we review the evidence for the success of these in pre‐clinical models and clinical trials, as single modality treatments and in combination with conventional cancer therapies. BioEssays 28:84–94, 2006. © 2005 Wiley Periodicals, Inc. (shrink)

The etiology of Tauopathies, a diverse class of neurodegenerative diseases associated with the Microtubule Associated Protein (MAP) Tau, is usually described by a common mechanism in which Tau dysfunction results in the loss of axonal microtubule stability. Here, we reexamine and build upon the canonical disease model to encompass other Tau functions. In addition to regulating microtubule dynamics, Tau acts as a modulator of motor proteins, a signaling hub, and a scaffolding protein. This diverse array of functions is related (...) to the dynamic nature of Tau isoform expression, post‐translational modification (PTM), and conformational flexibility. Thus, there is no single mechanism that can describe Tau dysfunction. The effects of specific pathogenic mutations or aberrant PTMs need to be examined on all of the various functions of Tau in order to understand the unique etiology of each disease state. (shrink)

The rate of human health care-associated infections caused by Acinetobacter baumannii has increased significantly in recent years for its remarkable resistance to desiccation and most antibiotics. Phospholipases, capable of destroying a phospholipid substrate, are heterologous group of enzymes which are believed to be the bacterial virulence determinants. There is a need for in silico studies to identify potential vaccine candidates. A. baumannii phospholipase D role has been proved in increasing organism’s resistance to human serum, destruction of host epithelial cell and (...) pathogenesis in murine model. In this in silico study high potentials of A. baumannii PLD in elicitation of humoral and cellular immunities were elucidated. Thermal stability, long half-life, non-similarity to human and gut flora proteome and non-allergenicity were in a list of A. baumannii PLD positive properties. Potential epitopic sequences were also identified that could be used as peptide vaccines against A. baumannii and various other human bacterial pathogens. (shrink)

Every living entity requires the capacity to defend against viruses in some form. From bacteria to plants to arthropods, cells retain the capacity to capture genetic material, process it in a variety of ways, and subsequently use it to generate pathogen-specific small RNAs. These small RNAs can then be used to provide specificity to an otherwise non-specific nuclease, generating a potent antiviral system. While small RNA-based defenses in chordates are less utilized, the protein-based antiviral invention in this phylum appears to (...) have derived from components of the same ancestral small RNA machinery. Based on recent evidence, it would seem that RNase III nucleases have been reiteratively repurposed over billions of years to provide cells with the capacity to recognize and destroy unwanted genetic material. Here we describe an overview of what is known on this subject and provide a model for how these defenses may have evolved. RNase III nuclease domains are widely used in an array of RNA metabolic functions as well as antiviral defenses. Here, we review their current usage as well as provide insight into how these domains may have shaped all major antiviral pathways over the course of evolution. (shrink)

Alzheimer's disease results from the degeneration of neurons. Degenerating nerve cells express atypical proteins, and amyloid is deposited. We suggest that some of these events are strongly influenced by genetic factors and age. Animal models should be useful in investigating the pathogenic mechanisms that lead to the brain abnormalities seen in this disease.

A total of 80 authors working in a variety of scientific disciplines commented on the theoretical model of CLimate, Aggression, and Self-control in Humans (CLASH). The commentaries cover a wide range of issues, including the logic and assumptions of CLASH, the evidence in support of CLASH, and other possible causes of aggression and violence (e.g., wealth, income inequality, political circumstances, historic circumstances, pathogen stress). Some commentaries also provide data relevant to CLASH. Here we clarify the logic and assumptions of (...) CLASH and discusses its extensions and boundary conditions. We also offer suggestions for future research. Regardless of whether none, some, or all of CLASH is found to be true, we hope it will stimulate future research on the link between climate and human behavior. Climate is one of the most presing issues of our time. (shrink)

In spite of extensive criticisms, war metaphors are still widespread in medical discourse. In the domain of public health analogies between war and infectious diseases are rooted in the similar impacts they can have on political institutions and communities. This similarity has been emphasized by the recent trend of addressing infectious disease from the point of view of national security. Nevertheless, it is here argued that the analogy cannot be used to model normative principles for treating carriers of contagious (...) diseases after the principles of ius in bello . Yet, the analogy may provide some useful practical and theoretical insights in tackling the growing problem of limiting the spread of drug-resistant pathogens: an issue that generates increasing worries and raises difficult ethical and political questions of rights, responsibilities and obligations. It is suggested that if anti-microbials and antibiotics are seen as strategic information, their misuse can be usefully compared to careless talk in times of war. (shrink)

Plants from a handful of species provide the primary source of food for all people, yet this source is vulnerable to multiple stressors, such as disease, drought, and nutrient deficiency. With rapid population growth and climate uncertainty, the need to produce crops that can tolerate or resist plant stressors is more crucial than ever. Traditional plant breeding methods may not be sufficient to overcome this challenge, and methods such as highOthroughput sequencing and automated scoring of phenotypes can provide significant new (...) insights. Ontologies are essential tools for accessing and analysing the large quantities of data that come with these newer methods. As part of a larger project to develop ontologies that describe plant phenotypes and stresses, we are developing a plant disease extension of the Infectious Disease Ontology (IDOPlant). The IDOPlant is envisioned as a reference ontology designed to cover any plant infectious disease. In addition to novel terms for infectious diseases, IDOPlant includes terms imported from other ontologies that describe plants, pathogens, and vectors, the geographic location and ecology of diseases and hosts, and molecular functions and interactions of hosts and pathogens. To encompass this range of data, we are suggesting inOhouse ontology development complemented with reuse of terms from orthogonal ontologies developed as part of the Open Biomedical Ontologies (OBO) Foundry. The study of plant diseases provides an example of how an ontological framework can be used to model complex biological phenomena such as plant disease, and how plant infectious diseases differ from, and are similar to, infectious diseases in other organism. (shrink)

We analyze the dynamics of nosocomial infections in intensive care units (ICUs) by using a Markov chain model. Since population size in the ICU is small, in contrast to previous studies, we concentrate on the analytical solution rather than using simulation. We investigate how changes in the system parameters affect to some important behavioral indicators of the spread of the pathogen. We also present an exact measure of the number of secondary cases of infection produced by one colonized patient.

The concept ‘hereditary breast cancer’ is commonly used to delineate a group of people genetically at risk for breast cancer—all of whom also having risk for other cancers. People carrying pathogenic variants of the BRCA1 and BRCA2 genes are often referred to as those having predisposition for ‘hereditary breast cancer’. The two genes, however, are when altered, associated with different risks for and dying from breast cancer. The main risk for dying for carriers of both genes is from ovarian (...) cancer. These biological facts are of philosophical interest, because they are the facts underlying the public debate on BRCA1/2 genetic testing as a model for the discussion of how to implement genetic knowledge and technologies in personalized medicine. A contribution to this public debate describing inherited breast cancer as ‘biological citizenship’ recently printed in Med Health Care and Philos illustrated how fragmented and detached from the biological and socio-political facts this debate sometimes is. We here briefly summarize some of the biological facts and how they are implemented in today’s healthcare based on agreed philosophical, ethical and moral principles. The suggestion of a ‘biological citizenship’ defined by hereditary breast cancer is incorrect and ill-advised. ‘Identity politics’ focusing hereditary breast cancer patients as a group based on a bundle of ill-defined negative arguments is well known, but is supported neither by scientific nor philosophical arguments. To those born with the genetic variants described, the philosophical rule of not doing harm is violated by unbalanced negative arguments. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:BLACK-ON-BLACK VIOLENCE: THE INTRAMEDIATION OF DESIRE AND THE SEARCH FOR A SCAPEGOAT Fred Smith Emory University René Girard's mimetic hypothesis provides a means of interpreting texts in terms of a systematic understanding ofcultural formations such as ritual, prohibition, and myth. It is based on an anthropology which accepts that most cultural texts are generated by an agency that does not appear explicitly or thematically within the texts themselves. That (...) generative agency is the scapegoat mechanism which I will discuss extensively in this essay as it concerns black-on-black violence in American society. With some modification, Girard's ideas account for the effects of the pathogenic educational environment to which black boys are exposed and which results in such violence. What we are witnessing in black-on-black violence may be understood in part as the consequence ofscapegoating which is driven by interdividual dynamics of desire analyzed in Girard's observations of mimetic behavior among humans. Mimetic desire is the starting point ofGirard's theory. Desire is mimetic in the sense that it imitates the desire of another. One's desire copies the other's desire for an object. Such desire is potentially violent because it can and often does lead to the rivalry of desires for the very same object. When mimetic desire is acquisitive, it produces violence at its most fundamental level. It is not that all mimetic desires "produce" violence, only acquisitive desire that becomes rivalrous or conflictual. I. The Triangle of Desire "Mimetic" comes from the same root as "mime" and "imitate." An acquisitive mimetic desire in Girard's theory involves the "desire to have" which imitates another person's desire for the possession or enjoyment ofan Fred Smith33 object. The object of desire may be a person or a thing; it can be a nonmaterial or metaphysical object like prestige, honor or "face" (pride). It is another who serves as the model for desiring a particular object. The greater the model's desire for the object, the greater the mimetic desire it inspires. The results are jealousy and covetousness over the possessions, positions or prestige, desired or enjoyed by the model of our desires. Desire is imitative because it is attracted to the object(s) belonging to another; furthermore, it is activated by the desire ofthe other, who may be a single person or an entire group. This imitative process requires that the subject have access to, or be able to appropriate and dispose of, the model's objects or possessions. Thus desire is triangular in its structure, being comprised ofthe subject, the other as model of desire, and the model's objects. Distance between the subject and model is an important factor in this structure. It does not necessarily denote physical space, for it can also function in terms ofpsychosocial space (i.e., race, socioeconomic position, cultural standing, etc.) (Redekop 7). Not only individuals, but society as a whole can serve as the model of desire. One also learns what is desirable from the aggregate of others that is society (Hamerton-Kelly 3). Acquisitive mimetic desire necessitates the ability of individuals to see themselves in the position ofthe model of desire. Ifthey are not able to see themselves in the place ofthe model, then the potential for the development of mimetic desire is minimal. This is why there is greater rivalry and jealously among slaves than between slave and master; among workers, rivalry is greater than between bosses and workers among siblings it is greater than between parents and children. This is the primary reason why violence is intraracial rather than interracial. II. Internal Mediation of Desire Mimetic desire is often reciprocal. Two people can be models ofdesire for each other, each one imitating the desire of the other for a common object. Acquisitive mimetic desire not only involves a desire to have, but includes the desire to be like, or even to be the other. This is why mimetic desire often evolves into love/hate relationships. An individual wants to be like the other, and simultaneously hates the other because he or she cannot be that other. The frustration of not being able to be another person or to have... (shrink)