Cancer: Towards a general theory of the target

General theories (GT) are reductionist explications of apparently independent facts. Here, in reviewing the literature, I develop a GT to simplify the cluttered landscape of cancer therapy targets by revealing they cluster parsimoniously according to only a few underlying principles. The first principle is that targets can be only exploited by either or both of two fundamentally different approaches: causality‐inhibition, and ‘acausal’ recognition of some marker or signature. Nonetheless, each approach must achieve both of two separate goals, efficacy (reduction in cancer burden) and selectivity (sparing of normal cells); if the mechanisms are known, this provides a definition of rational treatment. The second principle is target fragmentation, whereby the target may perform up to three categoric functions (cytoreduction, modulation, cytoprotection), potentially mediated by physically different target molecules, even on different cell types, or circulating freely. This GT remains incomplete until the minimal requirements for cure, or alternatively, proof that cure is impossible, become predictable.     

Studies of gonadal sex differentiation

Gonadal differentiation has a determinative influence on sex development in human embryos. Disorders of sexual development (DSD) have been associated with persistent embryonal differentiation stages. Between 1998 and 2015, 139 female patients with various (DSD) underwent operations at the Scientific Center of Obstetrics, Gynaecology and Perynatology in Moscow, Russia. Clinical investigations included karyotyping, ultrasound imaging, hormonal measurement and investigations of gonadal morphology. The male characteristics in the embryo are imposed by testicular hormones. When these are absent or inactive, the fetus may be arrested at between developmental stages, or stay on indifferent stage and become phenotypically female. A systematic analysis of gonadal morphology in DSD patients and a literature review revealed some controversies and led us to formulate a new hypothesis about sex differentiation. Proliferation of the mesonephric system (tubules and corpuscles) in the gonads stimulates the masculinization of gonads to testis. Sustentacular Sertoli cells of the testes are derived from mesonephric excretory tubules, while interstitial Leydig cells are derived from the original mesenchyme of the mesonephros. According of the new hypothesis, the original mesonephric cells (tubules and corpuscles) potentially persist in the ovarian parenchyma. In female gonads, some mesonephric excretory tubules regress and lose the tubular structure, but form ovarian theca interna and externa, becoming analogous to the sustentacular Sertoli cells in the testis. The ovarian interstitial Leydig cells are derived from intertubal mesenchyme of the mesonephros, similar to what occurs in male gonads (testis). Surprisingly, the leading determinative factor in sexual differentiation of the gonads is the mesonephros, represented by the embryonic urinary system.     

Social cognitive impairment and autism: what are we trying to explain?

Early psychological theories of autism explained the clinical features of this condition in terms of perceptual and sensory processing impairments. The arrival of domain-specific social cognitive theories changed this focus, postulating a ‘primary’ and specific psychological impairment of social cognition. Across the years, evidence has been growing in support of social cognitive and social attention explanations in autism. However, there has also been evidence for general non-social cognitive impairments in representational understanding, attention allocation and sensory processing. Here, I review recent findings and consider the case for the specificity and primacy of the social cognitive impairment, proposing that we should focus more explicitly on clinically valid features for insights on the integration of ‘social’ and ‘non-social’ cognition.     

A theoretical study of myoglobin working as a nitric oxide scavenger

The mechanism for the reaction between nitric oxide (NO) and O₂ bound to the heme iron of myoglobin (Mb), including the following isomerization to nitrate, has been investigated using hybrid density functional theory (B3LYP). Myoglobin working as a NO scavenger could be of importance, since NO reversibly inhibits the terminal enzyme in the respiration chain, cytochrome c oxidase. The concentration of NO in the cell will thus affect the respiration and thereby the synthesis of ATP. The calculations show that the reaction between NO and the heme-bound O₂ gives a peroxynitrite intermediate whose O–O bond undergoes a homolytic cleavage, forming a NO₂ radical and myoglobin in the oxo-ferryl state. The NO₂ radical then recombines with the oxo-ferryl, forming heme-bound nitrate. Nine different models have been used in the present study to examine the effect on the reaction both by the presence and the protonation state of the distal His64, and by the surroundings of the proximal His93. The barriers going from the oxy-Mb and nitric oxide reactant to the peroxynitrite intermediate and further to the oxo-ferryl and NO₂ radical are around 10 and 7 kcal/mol, respectively. Forming the product, nitrate bound to the heme iron has a barrier of less than ~7 kcal/mol. The overall reaction going from a free nitric oxide and oxy-Mb to the heme bound nitrate is exergonic by more than 30 kcal/mol.     

The diapause decision as a cascade switch for adaptive developmental plasticity in body mass in a butterfly

Switch‐induced developmental plasticity, such as the diapause decision in insects, is a major form of adaptation to variable environments. As individuals that follow alternative developmental pathways will experience different selective environments the diapause decision may evolve to a cascade switch that induces additional adaptive developmental differences downstream of the diapause decision. Here, we show that individuals following alternative developmental pathways in a Swedish population of the butterfly, Pararge aegeria, display differential optimization of adult body mass as a likely response to predictable differences in thermal conditions during reproduction. In a more northern population where this type of selection is absent no similar difference in adult mass among pathways was found. We conclude that the diapause decision in the southern population appears to act as a cascade switch, coordinating development downstream of the diapause decision, to produce adult phenotypes adapted to the typical thermal conditions of their expected reproductive period.     

The growth strategy of the Gram-positive rod

Abstract Bacteria grow by enlarging their envelope in such a way that osmotic pressure does not normally cause physical rupture. The strategy of Bacillus subtilis for both cylindrical elongation and pole formation is now substantially defined. Side-wall growth takes place by laying down new peptidoglycan, which is then displaced outwards, stretched and discarded; cross walls are laid down in the absence of stress, and then stretched and bulged outward as the septum is split and the pole is formed.     

The development of the critical theory of evolution: The scientific career of Wolfgang F. Gutmann

Summary The critical theory of evolution was developed by a group of scientists working together with Wolfgang F. Gutmann at the Senckenberg-Research-Institute in Frankfurt am Main. Gutmann worked at Senckenberg for 37 years. In this time he presented 247 contributions which are distributed over 47 periodicals and books. The ideas that were developed by Gutmann and his colleagues were innovative and pathbreaking for morphology and evolutionary biology. The large number of his morphological publications is indicative of the wide field that was opened up by the concepts of constructional morphology. As some of his colleagues have suggested, constructional morphology as an engineering approach to the study of organisms (i. e., engineering morphology) may replace the traditional concepts of morphology and anatomy and provides the observational base for the historical reconstruction of evolutionary pathways. Constructional morphology as a quasi-engineering approach can be the morphological pendant to the contemporary molecular approaches to biology, as it can provide the necessary morphological basis for the interpretation of the results of molecular studies in the light of evolution.     

Cartography and Clandestinité in Leïla Sebbar’s Shérazade: 17 ans, brune, frisée, les yeux verts

In this paper, I read Leïla Sebbar’s staging in her novel Shérazade: 17 ans, brune, frisée, les yeux verts of the resistance by children of North African and other immigrants in the early 1980s to the French state’s cartographic modes and documents of control. The paper will consider the many uses to which the map was put by the French state in its colonization of North Africa and particularly Algeria, and later in its attempts to control the banlieues its policies of citizenship and cartographic control yielded on the margins of Paris. In this context, I will explore the ways in which the novel’s characters, living clandestinely in a squatt, simultaneously resist, put to use, and even supercede state documents of control as they disrupt everyday life and conduct heists across the city of Paris. The paper will explore unofficial cartographies of Paris, from those afforded by the radios libres and alternative publications such as Libération and Sans Frontièrez, to oral and almost proverbial networks of knowledge criss-crossing the city of Paris, while also tracing the uses to which supplemental cartographic sketches and counterfeit identity cards are put in the pages of the novel. The paper will be in dialogue with theoretical and critical formulations of space, cartography, and state control put forward by Michel de Certeau, Henri Lefebvre, Michel Foucault, and Tom Conley. The paper will conclude with a consideration of the means and limits of resistance by the novel’s characters in the context of this body of theory and criticism.     

Use of time in a decision‐making process by a parasitoid

1. Time perception is seldom studied in invertebrates, with the limited experimental evidence being insufficient to provide a comprehensive pattern of the capacity of invertebrates to measure time and use it in decision‐making processes. 2. In this study, it was hypothesized that insect parasitoids have evolved the capacity to measure time precisely and to use it to optimize foraging decisions related to host exploitation. To examine time perception in females of the gregarious egg parasitoid Trichogramma euproctidis, the present study used their ability to adjust their investment (number of eggs laid) in a host to the initial transit duration (interval between the first contact with the host and the following contact with the substrate). Females utilize this method to assess host egg size, as a large egg necessarily requires more time to evaluate than a small host. In this study, the initial transit duration for a given sized egg was artificially extended by suspending it. 3. For similar sized hosts, female T. euproctidis significantly increased both oviposition duration and progeny allocation following a longer initial transit duration. 4. These results demonstrate the intrinsic capacity of this parasitoid to measure time and to adjust their progeny investment accordingly. This is believed to be one of the few demonstrations of a retrospective measure of time in an invertebrate.