Individual Fates Research Articles

A competitive coexistence principle?

Competitive exclusion – n species cannot coexist on fewer than n limiting resources in a constant and isolated environment – has been a central ecological principle for the past century. Since empirical studies cannot universally demonstrate exclusion, this principle has mainly relied on mathematical proofs. Here we investigate the predictions of a new approach to derive functional responses in consumer/resource systems. Models usually describe the temporal dynamics of consumer/resource systems at a macroscopic level – i.e. at the population level. Each model may be pictured as one time‐dependent macroscopic trajectory. Each macroscopic trajectory is, however, the product of many individual fates and from combinatorial considerations can be realized in many different ways at the microscopic – or individual – level. Recently it has been shown that, in systems with large enough numbers of consumer individuals and resource items, one macroscopic trajectory can be realized in many more ways than any other at the individual – or microscopic – level. Therefore, if the temporal dynamics of an ecosystem are assumed to be the outcome of only statistical mechanics – that is, chance – a single trajectory is near‐certain and can be described by deterministic equations. We argue that these equations can serve as a null to model consumer‐resource dynamics, and show that any number of species can coexist on a single resource in a constant, isolated environment. Competition may result in relative rarity, which may entail exclusion in finite samples of discrete individuals, but exclusion is not systematic. Beyond the coexistence/exclusion outcome, our model also predicts that the relative abundance of any two species depends simply on the ratio of their competitive abilities as computed from – and only from – their intrinsic kinetic and stoichiometric parameters.

Transnational movements between colonial empires: migrant workers from the British Cape Colony in the German diamond town of Lüderitzbucht

Before the First World War, there were significant transnational movements and interactions between colonies of different European powers in imperial Africa, a fact that is often neglected in research on imperial and colonial history. The paper addresses such movements, taking the town of Lüderitzbucht in the German colony of South West Africa as an example. Here, from 1908 onwards, a diamond boom attracted migrant workers from other colonies on a great scale, especially from the neighbouring British Cape. Lüderitzbucht is thus identified as a ‘transnational space’, where interactions between colonial states, conflicting interests of the German colonial administration and German business as well as the life and environment of African migrant workers can be investigated. The developments in Lüderitzbucht point to a growing interconnectedness during a period of worldwide globalisation that also reached the African colonies. German companies in particular were keen to explore the opportunities of a new migrant workforce. Conversely, the paper also stresses that such closer interactions led to a desire to demarcate a national style of colonial rule, especially in the case of the German colonial administration. The growing mixed society developing in Lüderitzbucht was obviously highly disturbing for the South West African government. The move of African workers from a British colony to a German colony also entailed a clash of different colonial cultures. As a further point, the focus on transnational connections highlights the otherwise hidden agency of African workers. Individual fates become visible through the use of new sources that would not be of interest to a history solely concentrating on the German or the British colony.

Automatic analysis of dividing cells in live cell movies to detect mitotic delays and correlate phenotypes in time

Live-cell imaging allows detailed dynamic cellular phenotyping for cell biology and, in combination with small molecule or drug libraries, for high-content screening. Fully automated analysis of live cell movies has been hampered by the lack of computational approaches that allow tracking and recognition of individual cell fates over time in a precise manner. Here, we present a fully automated approach to analyze time-lapse movies of dividing cells. Our method dynamically categorizes cells into seven phases of the cell cycle and five aberrant morphological phenotypes over time. It reliably tracks cells and their progeny and can thus measure the length of mitotic phases and detect cause and effect if mitosis goes awry. We applied our computational scheme to annotate mitotic phenotypes induced by RNAi gene knockdown of CKAP5 (also known as ch-TOG) or by treatment with the drug nocodazole. Our approach can be readily applied to comparable assays aiming at uncovering the dynamic cause of cell division phenotypes.

A single-cell pedigree analysis of alternative stochastic lymphocyte fates

In contrast to most stimulated lymphocytes, B cells exposed to Toll-like receptor 9 ligands are nonself-adherent, allowing individual cells and families to be followed in vitro for up to 5 days. These B cells undergo phases typical of an adaptive response, dividing up to 6 times before losing the impetus for further growth and division and eventually dying by apoptosis. Using long-term microscopic imaging, accurate histories of individual lymphocyte fates were collected. Quantitative analysis of family relationships revealed that times to divide of siblings were strongly related but these correlations were progressively lost through consecutive divisions. A weaker, but significant, correlation was also found for death times among siblings. Division cessation is characterized by a loss of cell growth and the division in which this occurs is strongly inherited from the original founder cell and is related to the size this cell reaches before its first division. Thus, simple division-based dilution of factors synthesized during the first division may control the maximum division reached by stimulated cells. The stochastic distributions of times to divide, times to die, and divisions reached are also measured. Together, these results highlight the internal cellular mechanisms that control immune responses and provide a foundation for the development of new mathematical models that are correct at both single-cell and population levels.

A novel view on stem cell development: analysing the shape of cellular genealogies

The analysis of individual cell fates within a population of stem and progenitor cells is still a major experimental challenge in stem cell biology. However, new monitoring techniques, such as high-resolution time-lapse video microscopy, facilitate tracking and quantitative analysis of single cells and their progeny. Information on cellular development, divisional history and differentiation are naturally comprised into a pedigree-like structure, denoted as cellular genealogy. To extract reliable information concerning effecting variables and control mechanisms underlying cell fate decisions, it is necessary to analyse a large number of cellular genealogies. Here, we propose a set of statistical measures that are specifically tailored for the analysis of cellular genealogies. These measures address the degree and symmetry of cellular expansion, as well as occurrence and correlation of characteristic events such as cell death. Furthermore, we discuss two different methods for reconstruction of lineage fate decisions and show their impact on the interpretation of asymmetric developments. In order to illustrate these techniques, and to circumvent the present shortage of available experimental data, we obtain cellular genealogies from a single-cell-based mathematical model of haematopoietic stem cell organization. Based on statistical analysis of cellular genealogies, we conclude that effects of external variables, such as growth conditions, are imprinted in their topology. Moreover, we demonstrate that it is essential to analyse timing of cell fate-specific changes and of occurrence of cell death events in the divisional context in order to understand the mechanisms of lineage commitment.

Understanding John McGahern

Understanding John McGahern surveys the life and work of the successful Irish novelist and short story writer whose career was launched with the 1963 publication of The Barracks. Most widely known for the 1998 film adaptation of Amongst Women, McGahern (1934-2006) has been enthusiastically received internationally and particularly in France, where some of the best and most extensive scholarship on his work has taken place. In this introduction to the writer and his body of work, David Malcolm identifies McGahern's primary concerns and assesses his popularity beyond the shores of Ireland. Although McGahern has long been categorized as a writer who specializes in the despair afflicting the Irish, Malcolm takes a broader view, showing how the novelist writes about individual fates that resonate with universal existential concerns. Malcolm discusses the autobiographical compass points of McGahern's work - rural northwest Ireland, a religious mother who dies prematurely, a domineering patriarch, a repressive and religious social order, 1950s and 1960s Dublin - and demonstrates that even singularly Irish situations relate to a larger twentieth-century reality. In individual chapters, Malcolm offers close readings of McGahern's novels and short stories, from The Barracks to That They May Face the Rising Sun/By the Lake. Malcolm's analyses include McGahern's controversial second novel, The Dark, which was banned by the Irish government. Malcolm shows the movement of McGahern's fiction from rural to urban and then back to rural settings, his novels' intertwining of individual and national histories, his insufficiently acknowledged technical experimentation, his depiction of existential despair and sexual malaise, and his hope for the future.

Good Neighbors (review)

Reviewed by: Good Neighbors April Spisak Thompson, Colin; Good Neighbors; illus. by Crab Scrambly. HarperCollins, 2008; 214p (The Floods) Library ed. ISBN 978-0-06-113199-8 $16.89 Trade ed. ISBN 978-0-06-113196-7 $15.99 R Gr. 3-5 In this Australian import, the familiar plot of a family with bad neighbors is cleverly upended when it turns out that the rotten folks next door are humans and the beleaguered Floods are a large family of witches and wizards. The Floods have tried being patient, ignoring the bordering trashy yard and annoying sounds, but they've finally reached their limit. Thus begins a series of "accidents" that happen to members of the neighboring Dent family (one is turned into a sophisticated refrigerator, [End Page 402] another is eaten by a long-buried zombie in the yard), the end result being, much to the Floods' delight, no more Dents. Thompson ably balances the several deaths and the macabre household in which the Floods live with humorous asides to the reader, absurd details about wizarding life, and a quick pace that keeps the reader from lingering too long on the individual fates of the Dents. In addition, as with the wretched children who visited Wonka's factory, the Dent family is so horrid, so exaggeratedly unappealing, that little sympathy will be spared for their fates anyway. Readers will be introduced to the Floods as much through the extensive end matter (files on each family member will aid significantly, for example, in sorting out the many children) and the numerous black-and-white illustrations as from the story itself, the first in a series. Even if young horror buffs don't spot the many nods to The Addams Family, they will certainly find this family, which gleefully breaks all the rules and considers bumping off neighbors a reasonable way to bring about peace, an intriguing and appealing group of protagonists. Pair this with Alan MacDonald's trolls vs. bad human neighbors tale Trolls, Go Home! (BCCB 9/07), and readers may never see the folks next door in quite the same way again. Copyright © 2008 The Board of Trustees of the University of Illinois

Single TNFalpha trimers mediating NF-kappaB activation: stochastic robustness of NF-kappaB signaling.

BackgroundThe NF-κB regulatory network controls innate immune response by transducing variety of pathogen-derived and cytokine stimuli into well defined single-cell gene regulatory events.ResultsWe analyze the network by means of the model combining a deterministic description for molecular species with large cellular concentrations with two classes of stochastic switches: cell-surface receptor activation by TNFα ligand, and IκBα and A20 genes activation by NF-κB molecules. Both stochastic switches are associated with amplification pathways capable of translating single molecular events into tens of thousands of synthesized or degraded proteins. Here, we show that at a low TNFα dose only a fraction of cells are activated, but in these activated cells the amplification mechanisms assure that the amplitude of NF-κB nuclear translocation remains above a threshold. Similarly, the lower nuclear NF-κB concentration only reduces the probability of gene activation, but does not reduce gene expression of those responding.ConclusionThese two effects provide a particular stochastic robustness in cell regulation, allowing cells to respond differently to the same stimuli, but causing their individual responses to be unequivocal. Both effects are likely to be crucial in the early immune response: Diversity in cell responses causes that the tissue defense is harder to overcome by relatively simple programs coded in viruses and other pathogens. The more focused single-cell responses help cells to choose their individual fates such as apoptosis or proliferation. The model supports the hypothesis that binding of single TNFα ligands is sufficient to induce massive NF-κB translocation and activation of NF-κB dependent genes.

Interactions Between Double-crested Cormorants and Herring Gulls at a Shared Breeding Site

The Double-crested Cormorant (Phalacrocorax auritus) population in the North American Great Lakes region has increased substantially during the past three decades. Cormorants are likely recovering after a period of human-caused suppression; however, their resurgence has raised concerns regarding potential negative interactions with other waterbirds. To examine this issue, we compared measures of nesting success and aggressive behavior in Herring Gulls (Larus argentatus) nesting on two artificial islands in Hamilton Harbour, western Lake Ontario. Only breeding Herring Gulls occupied the first island, whereas a mixed colony of both Herring Gulls and cormorants occupied the second. Over three years, Herring Gulls in the single-species colony had greater nesting success than those in the colony shared with cormorants. Gulls in the mixed colony had more nests that contained cormorant eggs in addition to Herring Gull eggs, or that were usurped by cormorants. Analysis of individual Herring Gull egg fates revealed lower hatching rates and more eggs displaced from nests in the mixed colony. Due to the presence of cormorants, gulls in the mixed colony engaged in more aggressive interactions near their nests than those in the single-species colony. We conclude that at our study site cormorants were competing directly with Herring Gulls for nest sites and nesting material, and contributing to reduced Herring Gull reproductive success in the mixed colony. Our results suggest that interactions between species in mixed colonies may be more subtle than the displacement of breeding adults, and may not be detected by examining nest counts alone. We suggest that further studies examine cormorant interactions with other colonial bird species at additional sites.

Molecular Markers of Neuronal Progenitors in the Embryonic Cerebellar Anlage

The cerebellum, like the cerebrum, includes a nuclear structure and an overlying cortical structure. Experiments in the past decade have expanded knowledge beyond the traditional function of the cerebellum to include critical roles in motor learning and memory and sensory discrimination. The initial steps in cerebellar development depend on inductive signaling involving FGF and Wnt proteins produced at the mesencephalic/metencephalic boundary. To address the issue of how individual cerebellar cell fates within the cerebellar territory are specified, we examined the expression of transcription factors, including mammalian homologues of LIM homeodomain-containing proteins, basic helix-loop-helix proteins, and three amino acid loop-containing proteins. The results of these studies show that combinatorial codes of transcription factors define precursors of the cerebellar nuclei, and both Purkinje cells and granule neurons of the cerebellar cortex. Examination of gene expression patterns in several hundred lines of Egfp-BAC (bacterial artificial chromosome) transgenic mice in the GENSAT Project revealed numerous genes with restricted expression in cerebellar progenitor populations, including genes specific for cerebellar nuclear precursors and Purkinje cell precursors. In addition, we identified patterns of gene expression that link granule and Purkinje cells to their precerebellar nuclei. These results identify molecular pathways that offer new insights on the development of the nuclear and cortical structures of the cerebellum, as well as components of the cerebellar circuitry.

Asymmetry of stem cell fate and the potential impact of the niche

Asymmetric cell division is a common concept to explain the capability of stem cells to simultaneously produce a continuous output of differentiated cells and to maintain their own population of undifferentiated cells. Whereas for some stem cell systems, an asymmetry in the division process has explicitly been demonstrated, no evidence for such a functional asymmetry has been shown for hematopoietic stem cells (HSC) so far. This raises the question regarding whether asymmetry of cell division is a prerequisite to explain obvious heterogeneity in the cellular fate of HSC. Through the application of a mathematical model based on self-organizing principles, we demonstrate that the assumption of asymmetric stem cell division is not necessary to provide a consistent account for experimentally observed asymmetries in the development of HSC. Our simulation results show that asymmetric cell fate can alternatively be explained by a reversible expression of functional stem cell potentials, controlled by changing cell-cell and cell-microenvironment interactions. The proposed view on stem cell organization is pointing to the potential role of stem cell niches as specific signaling environments, which induce developmental asymmetries and therefore, generate cell fate heterogeneity. The self-organizing concept is fully consistent with the functional definition of tissue stem cells. It naturally includes plasticity phenomena without contradicting a hierarchical appearance of the stem cell population. The concept implies that stem cell fate is only predictable in a probabilistic sense and that retrospective categorization of stem cell potential, based on individual cellular fates, provides an incomplete picture.

Mind wide open: your brain and the neuroscience of everyday life

BRILLIANTLY EXPLORING TODAY'S CUTTING-EDGE BRAIN RESEARCH, MIND WIDE OPEN IS AN UNPRECEDENTED JOURNEY INTO THE ESSENCE OF HUMAN PERSONALITY, ALLOWING READERS TO UNDERSTAND THEMSELVES AND THE PEOPLE IN THEIR LIVES AS NEVER BEFORE.Using a mix of experiential reportage, personal storytelling, and fresh scientific discovery, Steven Johnson describes how the brain works -- its chemicals, structures, and subroutines -- and how these systems connect to the day-to-day realities of individual lives. For a hundred years, he says, many of us have assumed that the most powerful route to self-knowledge took the form of lying on a couch, talking about our childhoods. The possibility entertained in this book is that you can follow another path, in which learning about the brain's mechanics can widen one's self-awareness as powerfully as any therapy or meditation or drug.In Mind Wide Open, Johnson embarks on this path as his own test subject, participating in a battery of attention tests, learning to control video games by altering his brain waves, scanning his own brain with a $2 million fMRI machine, all in search of a modern answer to the oldest of questions: who am I?Along the way, Johnson explores how we other people, how the brain processes frightening events (and how we might rid ourselves of the scars those memories leave), what the neurochemistry is behind love and sex, what it means that our brains are teeming with powerful chemicals closely related to recreational drugs, why music moves us to tears, and where our breakthrough ideas come from.Johnson's clear, engaging explanation of the physical functions of the brain reveals not only the broad strokes of our aptitudes and fears, our skills and weaknesses and desires, but also the momentary brain phenomena that a whole human life comprises. Why, when hearing a tale of woe, do we sometimes smile inappropriately, even if we don't want to? Why are some of us so bad at remembering phone numbers but brilliant at recognizing faces? Why does depression make us feel stupid?To read Mind Wide Open is to rethink family histories, individual fates, and the very nature of the self, and to see that brain science is now personally transformative -- a valuable tool for better relationships and better living.

POPULATION VIABILITY WITH FIRE IN ERYNGIUM CUNEIFOLIUM: DECIPHERING A DECADE OF DEMOGRAPHIC DATA

We analyzed and modeled the demography of Eryngium cuneifolium ,a n herbaceous species endemic to the fire-prone Florida scrub, using 10 annual censuses (1990- 1999) of 11 populations at Archbold Biological Station. Nearly every aspect of the de- mography of this plant is affected by time since fire. Year, time since fire, life history stage, and plant age affected survival, growth, and fecundity of E. cuneifolium, but time since fire and life history stage had the most consistent effects. Survival, flowering stem pro- duction, and early seedling survival were highest in recently burned sites. Long-term sur- vival, growth, and fecundity were highest for yearling cohorts recruiting recently after fire, with the largest contrast between plants recruiting two years postfire and those recruiting more than a decade postfire. Prior (historical) stage also affected individual plant fates. For example, plants with prior stasis or regression in stage subsequently died in greater numbers than plants with prior advancement in stage. Historical analyses did not suggest any cost associated with the initiation of flowering. We used a matrix selection approach to explicitly model Eryngium cuneifolium popu- lation viability in relation to fire. This simulation strategy included preserving observed data and variances within projection matrices formed for individual combinations of pop- ulation and year. We built 54 of these matrices, each with six stages (seed bank, yearlings, vegetative plants, and three reproductive stages). Each of these matrices also represented a specific time since fire. In building matrices, we minimized the use of pooled data while retaining specific matrices whenever possible. In this way, we preserved both the correlation structure within individual matrices (populations, years) and protected patterns among ma- trices across the time-since-fire gradient. To deal with less-detailed data on recruitment processes, we evaluated 13 fertility and seed bank scenarios that bracketed a range of outcomes. All scenarios were similar in showing the positive effects of fire on the demography of E. cuneifolium. The scenario with high seed bank survival (0.5) and low germination rates (0-0.005) was the best predictor of observed postfire years of peak aboveground population size (;8 yr) and aboveground population disappearance (30-34 yr), and also did a good job of reproducing observed population trajectories. Finite rates of increase (l) were .1 only during the first decade postfire but then declined beyond a decade postfire. Although prior (historical) stage affected most individual de- mographic parameters, it did not significantly influence finite rates of increase. Elasticities were highest for stasis and germination from the seed bank. Elasticities for survival in- creased with time since fire, while growth and fertility elasticities decreased. In historical models (those with information on stage from the second-to-last year), the elasticities for stasis were higher and the elasticities for growth lower, compared to models without this history. Bootstrapping suggested small standard errors for several types of model output. Most matrix elements were positively correlated, suggesting that favorable conditions affect many life history stages similarly, and that simulations using element selection would provide a less conservative risk assessment than the matrix selection technique used. We used a stochastic simulation program to simulate changing demography with time since fire, with various fire-return intervals, and for various initial population sizes. We obtained estimates of extinction risk and probability of population decline. Even populations as large as thousands of individuals will become extinct in the absence of fire. Fire-return intervals of 15 yr or less are necessary for E. cuneifolium persistence at individual sites. Fires at intervals longer than 20 yr create substantial extinction risks, and intervals longer than 12 yr produce declining populations. Cycles of widely divergent, alternating short and long fire-return intervals caused slightly higher chances of extinction compared to regular fire-return intervals. Although shrub regrowth is implicated in the decreased viability of E. cuneifolium populations under regimes of infrequent fire, aboveground fuel increases are often too slow

Discourses of Scandal: Bourgeois Respectability and the End of Slavery and Transportation at the Cape and New South Wales

Discourses of Scandal: Bourgeois Respectability and the End of Slavery and Transportation at the Cape and New South Wales, 1830 – 1850 Kirsten McKenzie The question of bonded labour, whether in the form of slavery or transportation, was amongst the most pressing issues occupying the collective mind of the British empire in the first half of the nineteenth century. These debates were concurrent with the emergence of a bourgeois imperial culture of manners which stressed the importance of personal respectability and domestic morality. If we examine the critiques mounted against slavery at the Cape and transportation to New South Wales in the 1830s we find that they were imbued with the discourses of sexual scandal. Similar objections were voiced against the resumption of transportation to New South Wales and the conversion of the Cape Colony to a penal settlement a decade later. The language of moral transgression which informed everyday social interaction, and which was invoked in private scandals, was also marshalled to promote and resist social change in the political arena. This discussion of the manner in which scandal (especially sexual scandal) became a propagandist tool to discredit the reputations of colonies supported by unfree labour draws on wider research about the place of scandal in constructing social boundaries within the colonial worlds of Cape Town and Sydney in the first half of the nineteenth century. Respectability had concrete implications in daily life for men and women who aspired to inclusion within the ranks of the colonial middle classes. It was a weapon to be wielded in the small politics of everyday life; the social competition whereby each would find their level in the new society. Reputation was equally important at the colony-wide level, and had implications for issues such as assisted emigration, political concessions to self-government, and investment.1 While scandals publicise the transgression of a society’s norms and values, such norms and values are contested features of social life, especially in communities undergoing such rapid social change as Sydney and Cape Town. They are not just, therefore, about the transgression of the culture of manners, but also ‘about the cultivation or assertion of the values or norms themselves’.2 Bonded labour was an especially troubling force in the construction of the bourgeois culture of empire. Tracing the elaboration of a respectable culture in two cities which had to deal with the problem of slavery and convict labour respectively is particularly pertinent to the broader question of white colonial reputation. While the Cape had a far longer history as a Dutch colonial settlement, by the 1830s Cape Town and Sydney belonged to established British colonies. Both, however, were troubled by debates over the impact of bonded labour. The transition to a new kind of society which was deemed worthy of self-government (a key aim of the urban bourgeoisie) was in part dependant upon the transition to a free labour system. Slavery and convict labour tainted the reputations of the Cape and New South Wales in the eyes of the metropole. This had both symbolic and practical effects. Both were used as arguments against giving the colonies representative government. At a deeper level, scandals deriving from the relations between masters and servants compromised white colonial efforts to represent Sydney and Cape Town as respectable communities. The small struggles to define respectability in the colonial setting were writ large in the debates over bonded labour. The trajectory of development in New South Wales and at the Cape was thus as strongly influenced by the emerging definitions of reputation as were the individual fates of their inhabitants. The 1830s saw an unprecedented wave of parliamentary investigation and the reform of diverse aspects of British imperial society, not least in the mother country itself. Although they built upon the achievements of the Tories in the 1820s, it was a trend associated with the ascendancy of the liberal Whigs, whose parliamentary victory in 1830 ushered in a decade heralded by its advocates as the ‘Age of Reform’. The enfranchisement of middle-class men through the Reform Act underlined the new world order which parliament increasingly endorsed. It was the culmination of a gradual process of change from the late eighteenth...

Nr0b1 and its network partners are expressed early in murine embryos prior to steroidogenic axis organogenesis

Ahch is an orphan nuclear receptor encoded by Nr0 b1 on the murine X chromosome and is the ortholog of human DAX1. Nr0 b1/ NR0 B1 expression at appropriate dosages is required for normal steroidogenic axis development: mutation of the human ortholog, NR0 B1, results in adrenal hypoplasia congenita and hypogonadotropic hypogonadism; and duplication or transgenic overexpression in humans or mice, respectively, results in XY phenotypic females, a phenotype known as dosage sensitive sex-reversal. Complete loss of Nr0 b1 by targeted deletion has been hypothesized to be lethal in embryonic stem (ES) cells and preliminary evidence suggested that ES cells might express Nr0 b1. These investigations examined Nr0 b1 expression and its network partners in both cultured ES cells and preimplantation embryos. We cultured ES cells in the absence or presence of differentiation agents and analyzed expression of Nr0 b1 and associated network partners by northern blot hybridization and reverse transcriptase-polymerase chain reaction. Nrob1 was highly expressed by totipotent ES cells with reduced expression following induction toward individual germ layer fates. Nr5 a1/ Sf1, Wt1 and other genes that encode proteins known to interact with Nr0 b1 were also expressed. Immunohistochemical analysis of preimplantation embryos for Ahch and key partners confirmed in vivo expression of network components. These findings are consistent with the existence of a potentially functional network of transcription factors, including Ahch, very early in embryonic development. These results validate ES cells as a developmentally dynamic model for mechanistic investigations into this regulatory network early in embryogenesis preceding organogenesis.

- Anatomy during the third reich - The institute of anatomy at the university of Marburg, as an example

A complete documentation of German anatomical science and its representatives during the period of national socialism has not been published as yet — contrary to the situation in other medical disciplines. Instead of German anatomists, American anatomists have occasionally addressed this issue during their meetings and have reported on special aspects, such as the use of Nazi symbols in anatomical textbooks and atlases (Pernkopf 1952) and the use of corpses of justice victims for anatomical research and student education. Also, the genesis of the atrocious collection of “racial” skulls, initiated along with the SS-institution of the “Ahnenerbe” by the anatomist August Hirt of Strasbourg (who ordered more than 90 inmates from concentration camps to be murdered in the gas chamber built in the concentration camp of Natzweiler-Struthof close to Strasbourg, Alsace) has been described by Frederic Kasten and others. A broader view of the patterns of behaviour and political actions and fates of contemporary scientists, ranging from dismissal to clandestine opportunism, affirmative cooperation and fanatic activism can be obtained by the analysis of the activities in research, medical education and academic positions of the following members of the Institute of Anatomy at the Philipp-University in Marburg: Ernst Göppert, Eduard Jacobshagen, Ernst-Theodor Nauck, Adolf Dabelow, Helmut Becher and Alfred Benninghoff, whose activities and fates differ in several respects and allow more general deductions. Also, the individual fates of a number of prosecuted Jewish anatomists (Wassermann, München; Poll, Hamburg), of devoted and active members of the Nazi party (Clara, Leipzig; Blotevogel, Breslau) and of criminal fanatics (Hirt, Strasbourg; Kremer, Münster) are briefly discussed. The present contribution is an attempt to initiate a more detailed study of all German departments of anatomy during the Hitler regime and to generate a public discussion among the younger generation of German anatomists.

Cross-repressive interactions of identity genes are essential for proper specification of cardiac and muscular fates in Drosophila.

In Drosophila embryos, founder cells that give rise to cardiac precursors and dorsal somatic muscles derive from dorsally located progenitors. Individual fates of founder cells are thought to be specified by combinatorial code of transcription factors encoded by identity genes. To date, a large number of identity genes have been identified; however, the mechanisms by which these genes contribute to cell fate specification remain largely unknown. We have analysed regulatory interactions of ladybird (lb), msh and even skipped (eve), the three identity genes specifying a subset of heart and/or dorsal muscle precursors. We show that deregulation of each of them alters the number of cells that express two other genes, thus changing the ratio between cardiac and muscular cells, and the ratio between different cell subsets within the heart and within the dorsal muscles. Specifically, we demonstrate that mutation of the muscle identity gene msh and misexpression of the heart identity gene lb lead to heart hyperplasia with similar cell fate modifications. In msh mutant embryos, the presumptive msh-muscle cells switch on lb or eve expression and are recruited to form supernumerary heart or dorsal muscle cells, thus indicating that msh functions as a repressor of lb and eve. Similarly, overexpression of lb represses endogenous msh and eve activity, hence leading to the respecification of msh and eve positive progenitors, resulting in the overproduction of a subset of heart cells. As deduced from heart and muscle phenotypes of numb mutant embryos, the cell fate modifications induced by gain-of-function of identity genes are not lineage restricted. Consistent with all these observations, we propose that the major role of identity genes is to maintain their restricted expression by repressing other identity genes competent to respond positively to extrinsic signals. The cross-repressive interactions of identity genes are likely to ensure their localised expression over time, thus providing an essential element in establishing cell identity.

Stories of Trauma and Idioms of Distress: From Cultural Narratives to Clinical Assessment

In the case of long-term major traumatic events such as the Cambodian tragedy there is a close relationship between the individual’s clinical history and the collective history of his/her ethnic group. Most of the refugees who have survived a given historical event share the same history with nearly the same trauma, the same loss, the same flight to escape, the same difficult resettlement and so on. However, even if refugees have lived the same events, this does not mean that they have experienced the same trauma. Both trauma and culture shape human experience and may give the illusion of a common destiny that would flatten out varying individual fates, whereas in fact different destinies are contingently linked together. These questions pose a challenge to clinicians’ knowledge of the relationship between trauma, culture and subjectivity and of course they challenge the concept of post-traumatic stress disorder as well. While knowledge of cultural differences is essential for clinicians, it is equally essential to be aware of how the individual’s psyche may find hidden paths within the constraints imposed by culture, or even by trauma itself. To illustrate this issue, the article focuses on the case study of a Cambodian refugee to France.

Wingless and Hedgehog pattern Drosophila denticle belts by regulating the production of short-range signals.

The secreted proteins Wingless and Hedgehog are essential to the elaboration of the denticle pattern in the epidermis of Drosophila embryos. We show that signaling by Wingless and Hedgehog regulates the expression of veinlet (rhomboid) and Serrate, two genes expressed in prospective denticle belts. Thus, Serrate and veinlet (rhom) partake in the last layer of the segmentation cascade. Ultimately, Wingless, Hedgehog, Veinlet (an indirect activator of the Egfr) and Serrate (an activator of Notch) are expressed in non-overlapping narrow stripes. The interface between any two stripes allows a reliable prediction of individual denticle types and polarity suggesting that contact-dependent signaling modulates individual cell fates. Attributes of a morphogen can be ascribed to Hedgehog in this system. However, no single morphogen organises the whole denticle pattern.

A Widespread and Early Requirement for a Novel Notch Function during Drosophila Embryogenesis

The Notch pathway plays a key role in the formation of many tissues and cell types in Metazoans. We recently showed that Notch acts in two pathways to determine muscle precursor fates. The first is the “standard” Notch pathway, in which Delta activates the Notch receptor, which then translocates into the nucleus in conjunction with Su(H) to reprogram transcription patterns and bring about changes in cell fates. The second pathway is poorly defined, but known to be independent of the ligands and downstream effectors of the standard pathway. The standard pathway is required in many different developmental contexts and we wondered if there was also a general requirement for the novel pathway. Here we show that the novel Notch pathway is required for the development of each of five examined cell types. These results indicate that the novel pathway is a widespread and fundamental component of Notch function. We further show that both Notch pathways operate in the differentiation of the same cell types. In such cases, the novel pathway acts first and appears to set up or limit the size of equivalence groups. The standard pathway then acts within the equivalence groups to limit individual cell fates.