You never know: Cdk inhibitors as anti-cancer drugs

Ever since it emerged that cyclin-dependent protein kinases catalysed cell cycle transitions, and with cancer seen as “A disease of the cell cycle”, people have pursued the aim of testing kinase inhibitors as anti-cancer drugs 1-4. Quite early on, Laurent Meijer and his colleagues discovered roscovitine as a potent inhibitor of Cdk1 5, and the compound went into clinical trials (as CYC202 or Seliciclib) whose outcomes are awaited 6-9. It was never clear to me that cancer was really a disease of the cell cycle (strictly speaking—considering that cancer cells have no trouble dividing), or how inhibiting cell cycle progression could reveal a window of therapeutic advantage between normal and neoplastic cells. Everyone knows what happens if you permanently block cell division in humans: they die. Yet, at the same time as harbouring doubts about the rationale for using anti-Cdk drugs for cancer therapy, I would also be the first to admit that our understanding of cell cycle control is so far from complete, that, given the relative ease of developing specific protein kinase inhibitors, it is not a bad idea to try and see if they have selective effects on tumours. You never know.     

The epistemic logic of asylum screening: (dis)embodiment and the production of asylum knowledge in Brazil

The current era demands our thoughtful attention to how states process asylum seeker claims for safe haven, yet we know little about the practices through which asylum officials carry out that work. Building from literature on the body and knowledge production, this paper illuminates the workings of (dis)embodiment in the asylum process. I use the term (dis)embodiment to refer to an arrangement of separate yet interdependent practices of disembodying and embodying knowledge. These practices of knowledge production together form an integral part of what I call the “epistemic logic” of asylum – the techniques and processes of reasoning used to produce and analyse information to determine if an asylum seeker qualifies for refugee status. Through an ethnography of the asylum process in Brazil, I document how officials produce and privilege disembodied knowledge, while they contrastingly constrain the knowledge of asylum seekers to their bodies and lived experiences.     

THE EVOLUTION OF SELECTIVE AGGRESSION CONDITIONED ON ALLORECOGNITION SPECIFICITY

Many sessile cnidarians deploy specialized structures while competing aggressively for living space. The initiation of aggression is often contingent on the relatedness of the interacting contestants; clonemates and close kin generally behave passively toward one another, whereas more distant relatives generally behave aggressively. Behavioral specificity of this sort requires that there be 1) an allorecognition system that can discriminate among subtle differences in cell-surface determinants and 2) a highly polymorphic genetic system that provides specific labels of relatedness (haplotypes or allotypes). The evoutionary models analyzed in this paper show that a population of individuals that behave aggressively only against haplotypically distinct individuals (discriminating phenotypes) will not be evolutionarily stable in the face of either unconditionally aggressive or unconditionally nonaggressive phenotypes. Furthermore, even if the discriminating trait were somehow fixed, the rare recognition alleles necessary to confer allotypic specificity could not become established through natural selection. Thus, allotypic specificity is unlikely to be maintained by individual selection acting directly through aggressive behavior. Other selective mechanisms might account for the evolution of allorecognition specificity. Allotypic polymorphism could be maintained by pleiotropic mechanisms in which rare alleles are favored by natural selection acting either on gametic incompatibility, pathogen resistance, or somatic fusion, rather than aggressive behavior per se. However, these mechanisms do not explain the maintenance of selective aggression based on allotypic differences. Alternatively, if aggressive members of a clone indirectly enhance the reproductive output or survival of the entire clone (or close relatives), then kin selection acting directly through aggressive behavior could favor allorecognition specificity. Choosing among these alternatives will require the development of more sophisticated theory and empirical analyses of the costs and benefits of aggression.     

The Tipping of the Big Stone—And Life itself. Obesity,Moral Work and Responsive Selves Over Time

Why is “everything I know is the right thing to do a million miles removed from what I do in reality?” This question posed by Rita, my main interlocutor and friend in a fieldwork that started in 2001–2003 and was taken up again in 2014–2015, opens up an exploration of moral work and moral selves in the context of the obesity epidemic and weight loss processes. I address these questions through the notion of “moral laboratories” taking up Mattingly’s argument that moral cultivation over time cannot be disconnected from a notion of self. Mattingly has consistently argued for a biographical and narrative self, which is processual and created in community. Along these lines, and by recourse to the German philosopher Bernhard Waldenfels’ phenomenology, I will propose the notion of a responsive self. The responsive self highlights the eventness of ongoing experimentation against the odds and captures equally pathic and agentive dimensions of a self that both persists and is transformed over time.     

"Bioplutonism" and the evolutionary implications of beneficial genes from another biosphere

Could exogenous genes from another biosphere have aided the evolution of life on Earth's surface over the last half-billion years? That possibility was considered by Thomas Gold in 1992, when he hypothesized that a “deep hot biosphere” (DHB) resides independently well below its cooler surface counterpart. And he suggested that “… in the long term … there may occasionally be beneficial exchanges of genetic material between microbial life at depth and the surface life.” Thus, the question: what evidence is there to support Gold's notion that exogenous genes from the DHB – let us call them “bioplutons” – ever bestowed benefits on the evolution of surface life? In pursuit of this question I drafted a null hypothesis: “Nothing beyond our own biosphere, as we know it today, renders any kind of genetic benefits to biological evolution.” After objectively analyzing the evidence and arguments pro and con I failed to reject the null hypothesis, given what we know today, especially the fact that no genetic imprint from the DHB has been identified in eukaryotic genomes. But my conclusion is regarded as tentative, because the fundamentals of Gold's argument, collectively referred to herein as “bioplutonism,” might be confirmed eventually with successful probes into the DHB, and with the sampling of its alleged genetic material.     

Sex,gender, and difference

Empirical research has demonstrated that women’s aggressive behavior is widespread and displays regularities across societies. Until recently, however, discussions about the aggressive behavior of women and gender differences in aggressive behavior have been based largely on data from nonhuman primates, children, or laboratory experiments. Using a unique corpus of naturalistic data on aggressive human interactions both between and among men and women, I explore the complexity of our questions about sex differences in aggression and further illuminate the ways in which men and women may use aggression in human interactions. In this paper I compare the aggressive behavior of men and women in an Australian Aboriginal community. In doing so I argue for the continuing use of a “sex differences” framework for organizing our understanding of gender relations and gender hierarchy. I believe, however, that this form of analysis benefits from, if not requires, a sensitivity to the most taken-for-granted aspects of our gender ideology and a commitment to attend to evidence that challenges our convictions about men and women.     

Emotions in robot psychology

In his famous thought experiments on synthetic vehicles, Valentino Braitenberg stipulated that simple stimulus-response reactions in an organism could evoke the appearance of complex behavior, which, to the unsuspecting human observer, may even appear to be driven by emotions such as fear, aggression, and even love (Braitenberg, Vehikel. Experimente mit künstlichen Wesen, Lit Verlag, 2004). In fact, humans appear to have a strong propensity to anthropomorphize, driven by our inherent desire for predictability that will quickly lead us to discern patterns, cause-and-effect relationships, and yes, emotions, in animated entities, be they natural or artificial. But might there be reasons, that we should intentionally “implement” emotions into artificial entities, such as robots? How would we proceed in creating robot emotions? And what, if any, are the ethical implications of creating “emotional” robots? The following article aims to shed some light on these questions with a multi-disciplinary review of recent empirical investigations into the various facets of emotions in robot psychology.     

The implicit rules of combat reflect the evolved function of combat: An evolutionary-psychological analysis of fairness and honor in human aggression

Aggression was a powerful selection pressure for our human ancestors. Aggressive contests would have selected not only for anatomical features (e.g., superior upper-body strength in adult males), but also for behavior-regulation adaptations for the conditional and cost-effective deployment of aggression. Here, we explore two concepts that appear to be part of the neurocognitive suite that regulates aggression. The first is the concept of a “fair fight”, which tags whether an aggressive bout can provide an unbiased estimate of the relative fighting ability of the combatants. The second concept is the “honorability” of a fighter, which tags whether an individual can be trusted to not inflict aggression in excess of what is needed to establish the relative fighting ability of the combatants. Eight predictions were derived from these hypotheses and tested experimentally with vignettes that varied relevant aspects of a fight. The results support the predictions. Fights are perceived as “fair” to the extent that the fighters avoid biased tactics that improve their probability of winning absent superior fighting ability (e.g., not attacking when the opponent is unprepared). Further, fighters are perceived as “honorable” when they minimize the danger to both combatants (e.g., not attacking after the opponent surrenders). We conclude by listing additional implications of the theory.     

The cultural construction of gendered bodies: Biology and metaphors of production and destruction*

One way of conceiving of the anthropological task is that of countering the degradations and “dehumanizations” of the “other” to which the species is prone by promoting “transcendent humanization.” However efficiently and professionally anthropologists gather their materials and form them into their ethnographic and ethnologic analyses, may not this “ethical impulse” be postulated as the “final cause” of our efforts? But what could such a sonorous phrase mean ? And what is its relationship to the systematic study of the “differences that make or do not make a difference” in culture to which anthropology has long been devoted? I will argue that it involves a dynamic of categories and that this dynamic is itself an object of systematic study. Recently, for example, some anthropologists have been writing “against culture,” seeing the culture concept and associated theory more as barriers than as benefits to pan‐human understanding. I will argue that this is an instance of “transcendent humanization.” One cannot but be sympathetic to the thrust and merits of this argument. But at the same time one wants to ask what implications it holds for the systematic study and understanding of the other. This article, then, examines some elementary vectors in the “dynamic of the categorical” involved in these and related recent debates which also may be seen in terms of transcendence and humanization: the debate over relativism and the recently emergent debate over “enlightenment mythmaking” in anthropology.     

Discovery of myosin I and Pollard-san

In this short review, I describe a brief history of the discovery of myosin I isolated from Acanthamoeba in 1973 by Tom Pollard and Ed Korn. Today, myosins form a large “family tree” that includes more than 30 types of myosins. I discuss the importance of the relationship among actin, myosin, and other actin-binding proteins, many of which were pioneered by Pollard-san (“-san” is a Japanese honorific suffix showing respect, politeness and friendship). At the first conference devoted to actin, Pollard-san, Korn-san, and I discussed the importance of the nucleotide bound at the two ends of the actin filament. I conclude that life is a dynamic accumulation of molecule-molecule bindings, and although we do not yet know how they coordinate with each other to operate a living cell, many enthusiastic and excellent researchers like Pollard-san will unveil mechanisms that will show us what life really looks like.     

Reimagining policy: Power,problems, and public stories

The authors of various practitioner and scholarly documents suggest markedly contrasting understandings about the nature of “policy.” These divergent conceptions raise the question: What is at stake by understanding the nature of policy in one way as opposed to another? The purpose of this philosophical inquiry is to interrogate the nature of “policy” as it relates to music education and to question the values that do and might underlie and propagate through contrasting understandings of “policy.” Subsequently, I examine two aspects of policy, problem identification and meaning-making, that have gone largely unexplored in the arts education literature.

Using Foucault's writings, I argue that power-laden policy texts often have the greatest impact, not when they are mandated, but when they go misrecognized as common sense. I also advocate for the consistent use of the terms “policy texts” and “policy actions,” including as an alternative to the imbalanced designations of “soft policies” and “hard policies.” Drawing on Dewey arts educators might form “publics” around problems having consequences that they deem far-reaching, recurrent, and irreparable. Individual and collective political narratives, including what Ganz explains as “stories of self,” “stories of us,” and “stories of now,” can foster the meaningful connections necessary for forming “publics” who address pressing problems in arts education.     

Visibilities,invisibilities and twilight zones at the crime scene in Portugal

The Police are the first element of a chain of custody culminating in the court. The documents they produce mediate the understandings between the crime scene and the court. Based on the formal rules, the police give visibility to the narrative and assign legitimacy and credibility to their performance. However, the decision to turn certain aspects of the narrative visible, leaving others in a twilight zone may have repercussions in the production of a verdict. Based in a qualitative analysis of three Portuguese judicial proceedings in this paper I explore how the narrative constructed by the police, based on what they see and what is unseen, travels between subepistemic cultures. Looking at the visibilities, invisibilities and twilight zones, I will try to understand how police forces at the crime scene in Portugal construct their narratives through the use of biological traces and how these narratives are part of the construction of the evidence. I argue that in criminal investigations in Portugal, the production of a narrative with legal meaning in court can be conditioned by the co-existence of the epistemic subcultures of police work (different police forces at the crime scene) that have different knowledge, practices, understandings and ways of “seeing” the forensic evidence. The degree of technological enthusiasm that guides the performance of different police forces at the crime scene is reflected in the way they “see” the scene and in the sociocultural understandings that they produce. This technological enthusiasm and what I call here “selective professional vision” are mobilized at the crime scene and can impact the robustness and efficiency of the evidence presented in court.     

Effects of group composition on agonistic behavior of captive pigtail macaques,Macaca nemestrina

We surveyed agonistic behaviors of 20 captive groups of pigtail macaques (Macaca nemestrina) housed under identical spatial conditions. Fifteen groups contained one male each; the other five groups contained no adult males. Groups included six to twelve adult females, some of which had infants with them. We found no relationship between social density of groups and incidence of agonistic behavior, but significantly more contact aggression (grab, hit, push, bite) and noncontact aggression (chase, open-mouth “threat,” bark vocalization) occurred among females in groups containing no males than in those containing one male each. Apparently, males played an important role in the inhibition of intragroup conflict. We also found that females in groups containing males exhibited less noncontact aggression if infants were present than if no infants resided in their groups. Thus, competition of females over infants must not have been an important constituent of intragroup conflict under the conditions of this survey.     

Neural mechanisms of persistent aggression

While aggression is often conceptualized as a highly stereotyped, innate behavior, individuals within a species exhibit a surprising amount of variability in the frequency, intensity, and targets of their aggression. While differences in genetics are a source of some of this variation across individuals (estimates place the heritability of behavior at around 25–30%), a critical driver of variability is previous life experience. A wide variety of social experiences, including sexual, parental, and housing experiences can facilitate “persistent” aggressive states, suggesting that these experiences engage a common set of synaptic and molecular mechanisms that act on dedicated neural circuits for aggression. It has long been known that sex steroid hormones are powerful modulators of behavior, and also, that levels of these hormones are themselves modulated by experience. Several recent studies have started to unravel how experience-dependent hormonal changes during adulthood can create a cascade of molecular, synaptic, and circuit changes that enable behavioral persistence through circuit level remodeling. Here, we propose that sex steroid hormones facilitate persistent aggressive states by changing the relationship between neural activity and an aggression “threshold”.     

Comparison of two introduction methods for African elephants (Loxodonta africana)

Managers must consider an animal's potential for aggression when they decide to change or form a captive social group formation. In this study we compared two introduction methods (termed “sequential” and “nonsequential” introductions) in African elephants to assess their effectiveness in managing aggression and minimizing stress. Both introduction methods included four phases: baseline, visual contact, limited tactile contact, and physical introduction. In the sequential introduction, these steps were followed sequentially, and empirical data were considered during decision‐making. In the nonsequential introduction, these steps were not followed sequentially, and decision‐making was based primarily on intuitive assessments by animal managers. Behavioral data and fecal corticoid concentrations were measured throughout both types of introduction. The behavior categories measured included active aggression, passive aggression, submissive behavior, undesirable/stress‐related behavior, and affiliative behavior. While the role of affiliative behavior was surprising, general behavior patterns were characterized by increases in behavior as animals progressed to the next phase of introduction regardless of introduction type. These increases then attenuated over time during each phase. Overall, less behavior was observed during the sequential introduction, as predicted. The data suggest that the sequential introduction managed aggression more effectively. Similar patterns were predicted for undesirable/stress‐related behavior and fecal corticoid concentration. Undesirable/stress‐related behavior was a poor predictor of observed behavior patterns. Although the patterns differed from those predicted, higher concentrations of fecal corticoids were measured during the nonsequential introduction and correlated significantly only with submissive behavior. While more investigation is warranted, the data indicate that the nonsequential introduction brought about an increased physiological response. Overall, the sequential introduction method appeared to manage aggression and stress better than the nonsequential technique. Every introduction is subject to factors that can influence success, such as staff experience, the design of the facility, and the animals' social histories. It is hoped that the rigorous sequential protocol will be a useful tool in the animal manager's “toolbox” for planning and implementing introductions. Applications of this introduction method are also discussed. Zoo Biol 23:109–126, 2004. © 2004 Wiley‐Liss, Inc.     

The sociobiology of ethnocentrism in an Indian City

In this article, I examine whether inter- and/or intraunit variation in ethnocentrism— a trait not automatically connected with mortality/natality rates—can be correlated with differential reproductive success. As a preliminary test of general theoretical models in the literature regarding the sociobiology of ethnocentrism, it was postulated that the more ethnocentric an ethnic unit is, the more important ethnocentrism is for the members of that unit. With the use of this postulate, hypotheses were generated and tested with empirical data obtained through field research among two ethnic units—Tamils and Gujaratis—in the city of Pune, India. It was concluded that: 1) if interunit aggression and kin selection were predominant characteristics of the early hominid environments of evolutionary adaptation, then from a sociobiological perspective, ethnocentrism can be explained as an evolved human trait, intimately linked to kin selection and interunit warfare; and, 2) under what I assumed to be novel environmental conditions ethnocentrism and reproductive success appear to be uncorrelated; and, 3) because the possibility exists that novel environmental contengencies were acting to level off reproductive variance upon which natural selection could have operated in my sample, only future research in a society similar in structure to those we tend to identify with early hominid environments of evolutionary adaptation will allow researchers to rule out the possibility that ethnocentrism is an evolved human “biocultural” trait.     

Reflections on the meanings of dreams prompted by reading Stekel.

What does it mean to interpret a dream? While reading Stekel, an underappreciated but fascinating author, I was struck both by his keen insights as well as his interpretive limitations. This led to broader questions concerning the polyvocal concept of “meaning” in the interpretation of dreams. This article suggests the meaning of dreams can include wish fulfillments, univocal translations, clarifying the life context, morphological equivalences, associations, and personal history. Stepping back, even the question of “interpretation” versus “appreciation” reminds us that the need, if any, for interpretation will vary depending on who is asking the question. Indeed, reflections on the “who” or ego in the dream leads beyond dreaming to ultimate questions concerning the reality of ego and meditative reflections on what it means to truly be awake and aware of life as it is. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adaptation to infectious disease. Australia antigen and hepatitis

Infectious diseases have probably acted as selective forces to generate polymorphisms in human populations. An example is given of a study related to this concept. There is evidence that “Australia antigen” is a hepatitis virus or closely associated with it. In some tropical populations there appears to be an inherited susceptibility to chronic infection with “Au(1) virus” controlled by a simple genetic mechanism. There are strikingly different frequencies of Australia antigen in different populations and these may have been determined by differences in the selective pressures in different environments.     

稳定同位素生物考古学的概念、简史、原理和目标

上世纪70年代末以降,考古遗址中出土生物材料的稳定同位素分析,在考古学和生物考古研究领域越来越发挥重要作用,成为现代考古学研究的重要组成部分。国内外学界常将其定位为分析技术,从未从学科层面予以考虑和重视。鉴于同位素分析的重要性以及学科发展的迫切性,将其由分析技术层面上升至学科层面实属大势所趋。本文将之前的"稳定同位素分析"首次命名为"稳定同位素生物考古学"(简称为同位素生物考古学),将其列为广义概念下生物考古学的重要学科分支之一。本文详细介绍了稳定同位素生物考古学的概念、研究简史、分析原理和研究目标;在分析原理上,除已有的"我即我食"和"我非我食"之外,还首次提出了"我即我是"和"我即我居";并对今后如何深入开展研究进行了展望。     

Walking back the cat: Unsupervised classification as an aid in “remote” fossil prospecting

Counterintelligence analysts use a technique called “walking back the cat'' to reveal “moles” or others passing on disinformation in which they compare what they now know as fact against what their agents or informers had told them to expect about certain persons or events. 1 Thus, “walking back the cat” is a perfect metaphor for working backwards; that is, retracing the complex development of an event and examining the “run up” to it in order to gain useful insights about how that event unfolded. Perhaps paleoanthropology can profit from such an approach.