Soma‐to‐germline feedback is forbidden under the neo‐Darwinian paradigm. Nevertheless, there is a growing realization it occurs frequently in immunoglobulin (Ig) variable (V) region genes. This is a surprising development. It arises from a most unlikely source in light of the exposure of co‐author EJS to the haplotype data of RL Dawkins and others on the polymorphism of the Major Histocompatibility Complex, which is generally assumed to be the most polymorphic region in the genome (spanning ∼4 Mb). The comparison between the (...) magnitude of MHC polymorphism with estimates for the human heavy chain immunoglobulin V locus (spanning ∼1 Mb), suggests IGHV could be many orders of magnitude more polymorphic than the MHC. This conclusion needs airing in the literature as it implies generational churn and soma‐to‐germline gene feedback. Pedigree‐based experimental strategies to resolve the IGHV issue are outlined. (shrink)

Although I am a molecular immunologist from another area of that wide discipline, for many years I have had a deep fascination with the whole topic of ancestral haplotypes. After recently reading an interesting article in this journal, “Reflections on the History and Ethics of the Proper Attribution and Misappropriation of Merit” , I was impelled to act and submit this essay for publication. The title of Gans’s article points to some of my own motivations. Gans outlines how (...) many important scientific discoveries are deliberately overlooked or inappropriately cited by contemporaries, or even completely misappropriated by undeserving scientists coming soon afterwards.It was Ceppellini and co-workers .. (shrink)

The common autoimmune disease type 1 diabetes provides a paradigm for the genetic analysis of multifactorial disease. Disease occurrence is attributable to the interaction with the environment of alleles at many loci interspersed throughout the genome. Their mapping and identification is difficult because the disease-associated alleles occur almost as commonly in patients as in healthy individuals; even the highest-risk genotypes bestow only modest risks of disease. The identification of common quantitative trait loci (QTL) in autoimmune disease and in other common (...) disorders, therefore,requires a very close marriage of genetics and biology. Two QTLs have been identified in human type 1 diabetes: the major histocompatibility complex HLA class II loci and a promoter polymorphism of the insulin gene. The evidence for their primary roles in disease aetiology demonstrates the necessity of combined studies of genetics and biology. Their functions and interaction underpin an emerging picture of the basic causes of the disease and direct analyses towards other candidate genes and pathways. The genetic tools used for QTL identification include transgenesis and gene knockouts, whole genome scanning for linkage, mouse congenic strains, linkage disequilibrium mapping, and the establishment of ancestral haplotypes among disease-associated chromosomes. BioEssays 1999;21:164–174. © 1999 John Wiley & Sons, Inc. (shrink)

Antigen presentation to CD8+ T cells by MHC class I molecules is essential for host defense against viral infections. Various mechanisms have evolved in multiple viruses to escape immune surveillance and defense to support viral proliferation in host cells. Through in vitro SARS‐CoV‐2 infection studies and analysis of COVID‐19 patient samples, we found that SARS‐CoV‐2 suppresses the induction of the MHC class I pathway by inhibiting the expression and function of NLRC5, a major transcriptional regulator of MHC class I genes. (...) In this review, we discuss the molecular mechanisms for suppression of the MHC class I pathway and clinical implications for COVID‐19. (shrink)

The role of the major histocompatibility complex (MHC) in mate choice in humans is controversial. Nowadays, the availability of genetic variation data at genomic scales allows for a careful assessment of this question. In 2008, Chaix et al. reported evidence for MHC‐dependent mate choice among European American spouses from the HapMap 2 dataset. Recently, Derti et al. suggested that this observation was not robust. Furthermore, when Derti et al. applied similar analyses to the HapMap 3 European American samples, they did (...) not see a significant effect. Although some of the points raised by Derti et al. are relevant, we disagree with the reported absence of evidence for MHC‐dependent mate choice within the HapMap samples. More precisely, we show here that the MHC dissimilarity among HapMap 3 European American spouses is still extreme in comparison to the rest of the genome, even after multiple testing correction. This finding supports the hypothesis of MHC‐dependent mate choice in some human populations. (shrink)

Receptors on cytotoxic T lymphocytes and natural killer cells play well‐established roles in the immunological response and share a common ligand in the form of MHC‐I. We discuss how a variety of MHC‐I receptors are also expressed on myelomonocytic cells such as macrophages and dendritic cells. Since myelomonocytic MHC‐I receptors recognise a broad range of alleles and MHC‐I structures, we propose that their task is to discern expression levels and folding forms of MHC. We describe a model in which these (...) recognition events would regulate bidirectional cross talk between cells of innate and adaptive immune systems to organise an ongoing combined immune response. We discuss how such a model is supported by recent literature and might function in a variety of contexts, including immunoregulation during pregnancy. Our model also offers an alternative explanation of immune dysregulation rather than autoimmunity during HLA‐B27‐associated spondyloarthropathies and addresses a number of conundrums in this field. BioEssays 27: 542–550, 2005. © 2005 Wiley periodicals, Inc. (shrink)

In Black Panther, T'Challa and Erik "Killmonger" Stevens experience audiences with their departed fathers. Careful analysis of the second and especially the third Ancestral Plane visits downplays the metaphysical, leading toward a metaphor for better understanding one's place in the world. M'Baku fights gallantly, but T'Challa prevails, and bolsters his worthiness for the throne by sparing M'Baku's life. T'Challa rises from the ground, not in the entombed Hall of Kings, but in what appears to be an African savanna where (...) the sky is rippled in majestic blues and purples, giving off a twilight ambiance. Ingesting it increases one's strength, speed, agility, and stamina. It is akin to Captain America's super soldier serum, which reminds us of that awesome footrace between T'Challa and Steve in Avengers: Infinity War. The Heart Shaped Herb potion, then, helps T'Challa and Killmonger achieve greater focus on each man's past and allows a better perspective on who each one. (shrink)

This paper introduces a class of graphical independence models that is closed under marginalization and conditioning but that contains all DAG independence models. This class of graphs, called maximal ancestral graphs, has two attractive features: there is at most one edge between each pair of vertices; every missing edge corresponds to an independence relation. These features lead to a simple parameterization of the corresponding set of distributions in the Gaussian case.

When Pythodorus in 411 B.C. moved in the Athenian Assembly his decree that Commissioners should be elected to draft measures for the security of the State, Cleitophon added a rider instructing the Commissioners προσαναξητσαι κα τος πατρονς νμονς ος κλειδθνης θηκεν τε καθδτη τν δημοκραταν, πως ν κοσαντες κα τοτων βολεσωντααι τ ριστον. The instruction appears to have struck Aristotle as paradoxical and inept, for he has appended an explanation of Cleitophon's reasons which is also a criticism: ς ο δημοτικν (...) λλ παραπλησαν οσαν τν Kλεισθνους πολιτεαν τ Σλωνος. Indeed one would never imagine that the constitution of Cleisthenes as described by Aristotle could have been seriously suggested as a model or a repertory of precedents for legislators intent, like Cleitophon's friends, on restoring the πτριος πολιτεα, which it obviously disestablished; and the conjunction of τοĐς πατρουσ with τε καθστη τν δημοκραταν might seem to make the proposal a challenge or a mockery. Aristotle had already given his opinion that by Cleisthenes' innovations δημοτικωτρα πολĐ τς Σλωνος γνετο πολιτεα He recognized democratic features in Solon's laws, but they lay in the redress of social wrongs or in the method of administering justice rather than in the organization of the government; he regarded Solon's political changes, not as the establishment of democracy proper, but as a reform, conservative rather than revolutionary, of existent institutions. His comment on the rider implies that he would not have corrected Cleitophon if he had referred the Commissioners to Solon's ancestral laws, but to refer them to Cleisthenes' must, he thought, be ignorance, irony, or idiosyncrasy. (shrink)

Neo-Fregeanism aims to provide a possible route to knowledge of arithmetic via Hume’s principle, but this is of only limited significance if it cannot account for how the vast majority of arithmetic knowledge, accrued by ordinary people, is obtained. I argue that Hume’s principle does not capture what is ordinarily meant by numerical identity, but that we can do much better by buttressing plural logic with plural versions of the ancestral operator, obtaining natural and plausible characterizations of various key (...) arithmetic concepts, including finiteness, equinumerosity and addition and multiplication of cardinality—revealing these to be logical concepts, and obtaining much of ordinary arithmetic knowledge as logical knowledge. Supplementing this with an abstraction principle and a simple axiom of infinity (known either empirically or modally) we obtain a full interpretation of arithmetic. (shrink)

The notion that eukaryotes are ancestrally sexual has been gaining attention. This idea comes in part from the discovery of sets of “meiosis‐specific genes” in the genomes of protists. The existence of these genes has persuaded many that these organisms may be engaging in sex, even though this has gone undetected. The involvement of sex in protists is supported by the view that asexual reproduction results in the accumulation of mutations that would inevitably result in the decline and extinction of (...) such lineages. It is argued that this phenomenon can be obviated by polyploidy and that the “meiosis‐specific genes” are used in other processes, including polyploidy control and homologous recombination, independent of meiosis. These phenomena account for the finding that these genes are expressed in cultures devoid of apparent cell fusion events. Hence, it is also proposed that asexual, and not sexual, reproduction is the ancestral condition. (shrink)

Various thinkers are concerned that the Orthodox view of Ancestral Sin does not avoid the age-old Augustinian concern of Pelagianism. After all, the doctrine of Ancestral Sin maintains that fallen human beings do not necessarily or inevitably commit actual sins. In contemporary literature, this claim could be articulated as a denial of the ‘inevitability thesis.’ A denial of the inevitability thesis, so contemporary thinkers maintain, seems to imply both that human beings can place themselves in right relation to (...) God as well as the Pelagian denial that all require Christ's work to attain this right relation to God. This article demonstrates that the Ancestral Sin, along with a denial of the inevitability thesis, is neither Pelagian nor Semi-Pelagian. I show that the doctrine of Ancestral Sin denies (Semi-) Pelagianism in various ways. I show that, for Ancestral Sin to entail (Semi-) Pelagianism, one must commit to several assumptions, each of which is plausibly deniable and none of which Orthodox thinkers affirm. (shrink)

Primatological and archaeological evidence along with anthropological accounts of hunter-gatherer societies indicate that lethal between-group violence may have been sufficiently frequent during our ancestral past to have shaped our evolved behavioral repertoire. Two simulations explore the possibility that heroism (risking one's life fighting for the group) evolved as a specialized form of altruism in response to war. We show that war selects strongly for heroism but only weakly for a domain-general altruistic propensity that promotes both heroism and other privately (...) costly, group-benefiting behaviors. A complementary analytical model shows that domain-specific heroism should evolve more readily when groups are small and mortality in defeated groups is high, features that are plausibly characteristic of our collective ancestral past. (shrink)

It is commonly assumed that the desire for a thin female physique and its pathological expression in eating disorders result from a social pressure for thinness. However, such widespread behavior may be better understood not merely as the result of arbitrary social pressure, but as an exaggerated expression of behavior that may have once been adaptive. The reproductive suppression hypothesis suggests that natural selection shaped a mechanism for adjusting female reproduction to socioecological conditions by altering the amount of body fat. (...) In modern Western culture, social and ecological cues, which would have signaled the need for temporary postponement of reproduction in ancestral environments, may now be experienced to an unprecedented intensity and duration. (shrink)

There is no consensus among scholars of myth as to how the central concept of their field should be defined. What is a ‘myth’ and how does it differ from a ‘belief’? Moreover, scholars have argued for a homological relationship between myth and ritual. Semantically, the word ‘myth’ has a connotation of disbelief in ‘superstition’, and the word ‘belief’ should be substituted when talking about religious practices. Likewise, the word ‘ritual’ may be substituted with ‘ceremonial’, which has connotations that are (...) more positive. Earlier publications that associate ancestral veneration with the words ‘myth’ or ‘superstition’ display a judgemental view of the beliefs of other cultures. In this article, the author attempts, via recourse to the use of the word ‘myth’, to describe and interpret traditional and cultural belief systems among the Bapedi people of Limpopo Province in South Africa. It is argued that myth should not be reduced to ritual nor ritual to myth. Belief and ritual, in Bapedi religion and belief systems, complete and complement each other, thus allowing the harmonious unison of meta and paralinguistic elements in religiocultural discourse. The focus of this study is to explore and document these links within the context of the Bapedi culture. (shrink)

Evolutionary medicine (EM) is an emerging field of medical studies that uses evolutionary theory to explain the ultimate causes of health and disease. The field’s main objective is to reconceptualize bodily vulnerabilities and pathophysiologies as evolutionary tradeoffs—many the result of an evolutionary mismatch between our ancient genome and modern lifestyle. This conceptual shift allows EM to describe health and disease in terms of adaptive functions and to prescribe treatments that best complement our evolved bodies. The goal is to “transform the (...) way patients and doctors see disease” (Nesse and Williams 1994, p. 245) in order to harness a renewed “feeling for the organism as a product of natural selection” .. (shrink)

The most challenging objections to the Threat Simulation Theory (TST) of the function of dreaming include such issues as whether the competing Random Activation Theory can explain dreaming, whether TST can accommodate the apparently dysfunctional nature of post-traumatic nightmares, whether dreams are too bizarre and disorganized to constitute proper simulations, and whether dream recall is too biased to reveal the true nature of dreams. I show how these and many other objections can be accommodated by TST, and how several lines (...) of new supporting evidence are provided by the commentators. Accordingly TST offers a promising new approach to the function of dreaming, covering a wide range of evidence and theoretically integrating psychological and biological levels of explanation. (shrink)

Stress is one of the most powerful experiences to influence health and disease. Through epigenetic mechanisms, stress may generate a footprint that propagates to subsequent generations. Programming by prenatal stress or adverse experience in parents, grandparents, or earlier generations may thus be a critical determinant of lifetime health trajectories. Changes in regulation of microRNAs (miRNAs) by stress may enhance the vulnerability to certain pathogenic factors. This review explores the hypothesis that miRNAs represent stress‐responsive elements in epigenetic regulation that are potentially (...) heritable. Recent findings suggest that miRNAs are key players linking adverse early environments or ancestral stress with disease risk, thus they represent useful predictive disease biomarkers. Since miRNA signatures of disease are potentially heritable, big data management platforms will be vital to harness multi‐generational information and capture succinct yet potent biomarkers capable of directing preventative treatments. This feature would offer a unique window of opportunity to advance personalized medicine. (shrink)

Current models for T‐cell recognition of foreign antigen depict the T‐cell receptor as having a single antibody‐like combining site which binds a complex of MHC and antigen. An alternative hypothesis is presented here; it is proposed that the first domains of the MHC function as inverted V‐like regions to complement the TcR V‐regions in creating antigen binding sites.

Thomas Richardson and Peter Spirtes. Scoring Ancestral Graph Models.

Many efforts have been made in recent years to construct formal systems for mechanizing general mathematical reasoning. Most of these systems are based on logics which are stronger than first-order logic. However, there are good reasons to avoid using full second-order logic for this task. In this work we investigate a logic which is intermediate between FOL and SOL, and seems to be a particularly attractive alternative to both: ancestral logic. This is the logic which is obtained from FOL (...) by augmenting it with the transitive closure operator. While the study of this logic has so far been mostly model-theoretical, this work is devoted to its proof theory. Two natural Gentzen-style proof systems for ancestral logic are presented: one for the reflexive transitive closure, and one for the non-reflexive one. We show that these systems are sound for ancestral logic and provide evidence that they indeed encompass all forms of reasoning for this logic that are used in practice. The two systems are shown to be equivalent by providing translation algorithms between them. We end with an investigation of two main proof-theoretical properties: cut elimination and constructive consistency proof. (shrink)

By using preimplantation haplotype diagnosis, prospective parents are able to select embryos to implant through in vitro fertilization. If we knew that the naturally-occurring (but theoretical) MoralKinder (MK+) haplotype would predispose individuals to a higher level of morality than average, is it permissible or obligatory to select for the MK+ haplotype? I.e., is it moral to select for morality? This paper explores the various potential issues that could arise from genetic moral enhancement.

Human infants are born ready to respond to affiliative signals of a caretaker's face, body, and voice. This ritualized behavior in ancestral mothers and infants was an adaptation that gave rise to music and dance as exaptations for promoting group ritual and other social bonding behaviors, arguing for an evolutionary relationship between mother and infant bonding and both music and dance.

McLuhan’s status as the patriarch of Canadian media studies is explored as a troublesome nomological principle in light of Derrida’s Archive Fever. The trouble with archives, for Derrida, is the trouble of the original source. Linking McLuhan’s exploration of typographical and electronic communication systems to Derrida’s deconstruction of the archive as a technology of exteriorization, this paper investigates the nature of subjectivity and objectivity in Western epistemology. Can the archive, conceived of as a medium, allow for an escape from the (...) specters of the past? Derrida’s proposed ‘archive of the future’ is theorized in terms of McLuhan’s sense of acoustic space and Foucault’s non-subjective discourse, and as a spatial and cultural construct reflecting the technological uncertainty in an age of mixed-media. (shrink)

Fourteen essays consider the interaction between Greek philosophy and Jewish religious thought during the Hellenistic period. Attention is paid to the work of Ben Sira, Solomon, and Philo of Alexandria, especially concerning issues like stoicism, freedom and determinism, creation, mysticism, and sex. Attempts to find a synthesis of Jewish and Greek thought are emphasized. Author and title index only. c. Book News Inc.

This short article discusses the fact that the word ‘ancestor’ features in certain arguments that a) are apparently logically valid, b) contain infinitely many premises, and c) are such that none of their finite sub-arguments are logically valid. The article's aim is to motivate, within its brief compass, the study of infinitary logics.

The revitalization of Indigenous ways of knowing and being with land is central to addressing the devastating impacts of climate change. This article contributes to growing research in Indigenous Climate Change Studies by focusing on connections between ecology, sexuality, and gender. To track the histories of gendered violence for Two Spirit peoples is to also follow the marked wounds of land dispossession, excavation, and exploitation. Conversely, Two Spirit futures are deeply imbricated in not only surviving but also flourishing among post-apocalyptic (...) conditions. Through socio-linguistic analyses of western animacy hierarchies and a historical analysis of colonial fables which casted the racialized-gendered other as monstrous, this article critiques popularized end-of-the-world discourses on climate change narratives. Alternatively, the article concludes by offering a reading of Indigiqueer speculative science fiction, gleaning methods of not only survival and resistance but also resilience amongst post-apocalyptic conditions. Ultimately, this paper argues that the revitalization of Indigenous genders is in-part linked to the present revitalization and protection of ecological life-worlds, centering Two Spirit knowledge at what settlers may fear to be “the end of the world.”. (shrink)

After presenting the ordinary and the Fregean formulations of the ancestral, I raise the question of what is their relationship, the natural candidate being that the Fregean version is an analysans intended to improve upon, and replace, the common notion of ancestral (the analysandum). Next, two types of circles that arise in connection with the Fregean ancestral are presented, and it is claimed that one of the circles makes it impossible to maintain the just described (“replacement”) interpretation. (...) A reference is made to Kerry, who was the first to point out a circularity in Frege’s ancestral. Some of Frege’s remarks are examined in order to tentatively sketch, an answer to the issue of the relationship between ordinary and Fregean ancestral; the latter, if not as an analysans replacing the common notion, can still be seen as a profound enrichment of the former. (shrink)

Phenomena like meat sharing in hunter-gatherers, self-sacrifice in intergroup conflicts, and voluntary contribution to public goods provision in laboratory experiments have led to the development of numerous theories on the evolution of altruistic in-group beneficial behavior in humans. Many of these theories abstract away from the effects of kinship on the incentives for public goods provision, though. Here, it is investigated analytically how genetic relatedness changes the incentive structure of that paradigmatic game which is conventionally used to model and experimentally (...) investigate collective action problems: the linear public goods game. Using recent anthropological data sets on relatedness in 61 contemporary hunter-gatherer and horticulturalist societies the relevant parameters of this model are then estimated. It turns out that the kinship patterns observed in these societies substantially reduce the negative effect of increasing group size on incentives for public goods provision. It is suggested, therefore, that renewed attention should be given to inclusive fitness theory in the context of public goods provision also in sizable groups, because its explanatory power with respect to this central problem in the evolution of human cooperativeness and altruism might have been substantially underrated. (shrink)

Famously, in his seminal After Finitude, Quentin Meillassoux charges Heidegger with what he classifies as strong correlationism. In general,...

Human evolution explains how we have found ourselves in the wrong place at the wrong time. Issues of modern living; depression, obesity, and environmental destruction, can be understood in relation to our evolutionary past. This book shows how an awareness of this past and its relation to the present can help limit their impact on the future.

Graphical AbstractMHC II, a major feature of the adaptive immune system, is lacking in Atlantic cod, and there are different scenarios (metabolic cost hypothesis or functional shift hypothesis) that might explain this loss. The lack of MHC II coincides with an increased number of genes for MHC I and Toll-like receptors (TLRs).

Problems of Han Administration: Ancestral Rites, Weights and Measures, and the Means of Protest. By Michael Loewe. Leiden: Brill, 2016. Pp. xi + 326. €114, $137.

Causal reasoning is primarily concerned with what would happen to a system under external interventions. In particular, we are often interested in predicting the probability distribution of some random variables that would result if some other variables were forced to take certain values. One prominent approach to tackling this problem is based on causal Bayesian networks, using directed acyclic graphs as causal diagrams to relate post-intervention probabilities to pre-intervention probabilities that are estimable from observational data. However, such causal diagrams are (...) seldom fully testable given observational data. In consequence, many causal discovery algorithms based on data-mining can only output an equivalence class of causal diagrams. This paper is concerned with causal reasoning given an equivalence class of causal diagrams, represented by a ancestral graph. We present two main results. The first result extends Pearl 's celebrated do-calculus to the context of ancestral graphs. In the second result, we focus on a key component of Pearl's calculus---the property of invariance under interventions, and give stronger graphical conditions for this property than those implied by the first result. The second result also improves the earlier, similar results due to Spirtes et al. (shrink)

The kin selection hypothesis posits that male androphilia (male sexual attraction to adult males) evolved because androphilic males invest more in kin, thereby enhancing inclusive fitness. Increased kin-directed altruism has been repeatedly documented among a population of transgendered androphilic males, but never among androphilic males in other cultures who adopt gender identities as men. Thus, the kin selection hypothesis may be viable if male androphilia was expressed in the transgendered form in the ancestral past. Using the Standard Cross-Cultural Sample (...) (SCCS), we examined 46 societies in which male androphilia was expressed in the transgendered form (transgendered societies) and 146 comparison societies (non-transgendered societies). We analyzed SCCS variables pertaining to ancestral sociocultural conditions, access to kin, and societal reactions to homosexuality. Our results show that ancestral sociocultural conditions and bilateral and double descent systems were more common in transgendered than in non-transgendered societies. Across the entire sample, descent systems and residence patterns that would presumably facilitate increased access to kin were associated with the presence of ancestral sociocultural conditions. Among transgendered societies, negative societal attitudes toward homosexuality were unlikely. We conclude that the ancestral human sociocultural environment was likely conducive to the expression of the transgendered form of male androphilia. Descent systems, residence patterns, and societal reactions to homosexuality likely facilitated investments in kin by transgendered males. Given that contemporary transgendered male androphiles appear to exhibit elevated kin-directed altruism, these findings further indicate the viability of the kin selection hypothesis. (shrink)

Este artigo fala sobre a influência das religiões sobre nossos corpos, primeiramente o catolicismo, que no pretexto de salvar almas bárbaras e hereges tentou catequizar os índios e os negros para domesticar seus corpos, e dos negros que trazem consigo uma forte cultura ancestral centrada no corpo para o Brasil. Durante a colonização e diáspora aconteceu um forte encontro cultural que construiu uma maneira própria de ser no mundo do afrodescendente. O texto em si está fundamentado na mitologia, uma (...) vez que o mito é a maneira primordial de ser no mundo e na cultura popular nas músicas de Carlinhos Brown e Clara Nunes. Discute sobre a sexualidade dos orixás, seu encontro na umbanda com os ciganos, falando de Maria Padilha, a rainha da sedução, que é um dos exus femininos mais populares. A sensualidade em pessoa, Maria Padilha vai fazer parte da umbanda e da maioria dos candomblés, sendo responsável pelos problemas de cunho amoroso. O texto aprofunda, também, conceitos como ancestralidade, comunicação cultural, inversão exuriana e identidade. (shrink)

In this paper, I address a range of arguments put forward by Katrin Flikschuh (2016) casting doubts on a theoretical account ofancestral persons in the work of Ifeanyi Menkiti. She argues both that their ontological status is uncertain and that they areontologically redundant. I argue that she does not succeed in convincing us to settle for a practical justification of ancestors. Ithen supplement Menkiti’s life-history account of post-mortem persistence with Searle’s account of social ontology with a viewto theoretically justify belief (...) in the existence of ancestral persons. (shrink)