The aging of the 2000 and 2011 Hallmarks of Cancer reviews: A critique

Two review articles published in 2000 and 2011 by Hanahan and Weinberg have dominated the discourse about carcinogenesis among researchers in the recent past. The basic tenets of their arguments favour considering cancer as a cell-based, genetic disease whereby DNA mutations cause uncontrolled cell proliferation. Their explanation of cancer phenotypes is based on the premises adopted by the somatic mutation theory (SMT) and its cell-centered variants. From their perspective, eight broad features have been identified as so-called ‘Hallmarks of Cancer’. Here, we criticize the value of these features based on the numerous intrinsic inconsistencies in the data and in the rationale behind SMT. An alternative interpretation of the same data plus data mostly ignored by Hanahan and Weinberg is proposed, based instead on evolutionarily relevant premises. From such a perspective, cancer is viewed as a tissue-based disease. This alternative, called the tissue organization field theory, incorporates the premise that proliferation and motility are the default state of all cells, and that carcinogenesis is due to alterations on the reciprocal interactions among cells and between cells and their extracellular matrix. In this view, cancer is development gone awry.     

Tests of the heterosis model

Summary An alternative to the classical model of self-incompatibility indicates that genetic control of self-incompatibility could involve more than one locus and function through passive failure of incompatible pollen tubes rather than through their active inhibition. Both aspects of the alternative model have been tested and, in each case, the data support the classical single-locus oppositional interpretation rather than the alternative. On the basis of these data, and others now available, we conclude that, in the Solanaceae, and presumably also in some others, self-incompatibility is better explained by the classical interpretation. Several points, however, remain to be resolved.     

A revised hypothesis on the evolutionary origin of the vertebrate dentition

Despite claims to the contrary, the evolutionary origin of teeth has not been definitely established. The classical ‘outside in’ theory stating that teeth derive from odontodes that invaded the oral cavity in conjunction with the origin of jaws has been challenged by an alternative, ‘inside out’, hypothesis suggesting that teeth evolved from pharyngeal denticles, as endodermal derivatives, prior to the origin of jaws. We propose a third scenario, a revised ‘outside in’ hypothesis ( Huysseune et al., 2009 ). Our hypothesis is consistent with the current data and avoids speculations about convergent tooth evolution. We suggest that teeth may indeed have arisen before the origin of jaws, a pillar of the ‘inside out’ hypothesis, but not from the endodermally lined posterior pharynx. Rather, teeth would have been the result of competent, odontode‐forming ectoderm invading the oropharyngeal cavity through the mouth as well as through the gill slits, interacting with neural‐crest derived mesenchyme. Arguments in support of this hypothesis are: (i) the observation that pharyngeal teeth are present only in species known to possess gill slits, and disappear from the pharyngeal region in early tetrapods concomitant with the closure of gill slits; (ii) the assumption that endoderm alone, together with neural crest, cannot form teeth; (iii) observations on pharyngeal tooth and gill slit formation in extant species; (iv) the observation that the dental lamina (sensu Reif, 1982 ) is not a prerequisite for tooth formation; (v) evidence that patterning does not distinguish pharyngeal from skin denticles, and (vi) the observation on zebrafish mutants affected in the dermal skeleton. This ‘modified outside in’ hypothesis can be tested both on paleontological data (it predicts a correlation of the presence of pharyngeal teeth and of gill slits), and on developmental data in extant species (it predicts the necessity of an ectodermal signal to make [pharyngeal] teeth).     

The identification of inducible cytoplasmic/nuclear carbohydrate-binding proteins urges to develop novel concepts about the role of plant lectins

During the last few years compelling evidence has been presented for the occurrence of cytoplasmic/nuclear plant lectins that are not detectable in normal plants but are only induced upon application of well-defined stress conditions. Since both the regulation of the expression and the subcellular location indicate that these ‘non-classical lectins’ are good candidates to play a physiologically important role as mediators of specific protein-carbohydrate-interactions within the plant cell, a critical assessment is made of the impact of these findings on the development of novel concepts about the role of plant lectins. Based on an analysis of the biochemical, molecular and evolutionary data of a jasmonate-induced chitin-binding lectin from tobacco leaves and a salt/jasmonate-induced leaf lectin from rice it is concluded that these lectins most probably interact with endogenous glycans located within the cytoplasmic/nuclear compartment of the plant cell. Several working mechanisms are proposed to explain how these inducible lectins may fulfill an important regulatory or structural role in stressed cells. In addition, the question of the evolutionary relationship(s) between the newly discovered inducible lectins and their ‘classical’ constitutively expressed homologs is addressed. Evidence is presented that the ‘non-classical lectins’ represent the main evolutionary line and that some of their corresponding genes were used as templates for genes encoding storage protein-like ‘classical’ homologs. Published in 2004.     

The PVC superphylum: exceptions to the bacterial definition?

The PVC superphylum is a grouping of distinct phyla of the domain bacteria proposed initially on the basis of 16S rRNA gene sequence analysis. It consists of a core of phyla Planctomycetes, Verrucomicrobia and Chlamydiae, but several other phyla have been considered to be members, including phylum Lentisphaerae and several other phyla consisting only of yet-to-be cultured members. The genomics-based links between Planctomycetes, Verrucomicrobia and Chlamydiae have been recently strengthened, but there appear to be other features which may confirm the relationship at least of Planctomycetes, Verrucomicrobia and Lentisphaerae. Remarkably these include the unique planctomycetal compartmentalized cell plan differing from the cell organization typical for bacteria. Such a shared cell plan suggests that the common ancestor of the PVC superphylum members may also have been compartmentalized, suggesting this is an evolutionarily homologous feature at least within the superphylum. Both the PVC endomembranes and the eukaryote-homologous membrane-coating MC proteins linked to endocytosis ability in Gemmata obscuriglobus and shared by PVC members suggest such homology may extend beyond the bacteria to the Eukarya. If so, either our definition of bacteria may have to change or PVC members admitted to be exceptions. The cases for and against considering the PVC superphylum members as exceptions to the bacteria are discussed, and arguments for them as exceptions presented. Recent critical analysis has favoured convergence and analogy for explaining eukaryote-like features in planctomycetes and other PVC organisms. The case is made for constructing hypotheses leaving the possibility of homology and evolutionary links to eukaryote features open. As the case of discovery of endocytosis-like protein uptake in planctomycetes has suggested, this may prove a strong basis for the immediate future of experimental research programs in the PVC scientific community.     

The lapsed and the laity: discipline and lenience in the study of religion

This article cautions against an ‘earnest turn’ within the anthropology of religion, pointing up the tendency for anthropologists of religion to over‐emphasize the role of discipline in the construction of the religious subjecthood over mechanisms of leniency and compromise. Taking the Catholic Church as an example, I show how discipline and lenience have been co‐constitutive of Christian subjectivities, as different movements in a gigantic choreography which have spanned and evolved over several centuries. By looking at certain technologies of lenience that have emerged over the course of Catholic history, I trace an alternative genealogy of ‘the Christian self’; one in which institutional growth, power, and survival depended not only upon the formation of disciplined bodies and interior dispositions but also upon a carefully managed division of labour between clergy and laity, as well as upon a battery of legal commutations and practical avoidances aimed at minimizing the effort and pain of the ascetic approach. Taking the concept of ‘lapsedness’ as cue, I ask to what extent the ‘lapsed Catholic’, rather than indexing an ever‐increasing tendency towards secularism, might already be contained and accounted for within Catholicism as a living, evolving form.     

The Compartmentalized Bacteria of the Planctomycetes-Verrucomicrobia-Chlamydiae Superphylum Have Membrane Coat-Like Proteins

The development of the endomembrane system was a major step in eukaryotic evolution. Membrane coats, which exhibit a unique arrangement of β-propeller and α-helical repeat domains, play key roles in shaping eukaryotic membranes. Such proteins are likely to have been present in the ancestral eukaryote but cannot be detected in prokaryotes using sequence-only searches. We have used a structure-based detection protocol to search all proteomes for proteins with this domain architecture. Apart from the eukaryotes, we identified this protein architecture only in the Planctomycetes-Verrucomicrobia-Chlamydiae (PVC) bacterial superphylum, many members of which share a compartmentalized cell plan. We determined that one such protein is partly localized at the membranes of vesicles formed inside the cells in the planctomycete Gemmata obscuriglobus. Our results demonstrate similarities between bacterial and eukaryotic compartmentalization machinery, suggesting that the bacterial PVC superphylum contributed significantly to eukaryogenesis.     

The female postabdomen and internal genitalia of the basal moth genus Agathiphaga (Insecta: Lepidoptera: Agathiphagidae): morphology and phylogenetic implications

The female postabdomen of Agathiphaga vitiensis terminates in a telescope‐type extensible oviscapt with an apial ‘oviscapt probe’ composed of fused segments behind VIII. Exceptionally within the Lepidoptera two pairs of long ‘anterior apophyses’ arise from segment VIII, from the dorsum and venter. Agathiphaga has the most elaborate postabdominal musculature recorded from female Lepidoptera, comprising 24 muscle sets of which nine may be family autapomorphies. Apophysis musculature does not permit unambiguous homologizing of the single anterior apophysis in Lepidoptera–Glossata with either the dorsal or ventral pair in Agathiphaga, but is compatible with an interpretation of the glossatan anterior apophyses as a composite formation. Nine muscle sets shared with rhyacophilid caddisflies are ascribed to the amphiesmenopteran ground plan. The spermathecal duct represents an intermediate stage between the simple type present in Micropterigidae and the ‘two‐compartment type’ characteristic of almost all other Lepidoptera. The spermatheca has no lagena. The bursa copulatrix is small and simple. Accessory glands are very large, simple sacs. There are 40 + ovarioles per ovary. A terminal cloaca is extremely short. The numerous ovarioles potentially support a sister‐group relationship between Agathiphagidae and all other Lepidoptera, whereas the spermathecal duct histology supports the alternative conservative placement of the family as sister group of all nonmicropterigid Lepidoptera. © 2010 The Linnean Society of London, Zoological Journal of the Linnean Society, 2010, 159 , 905–920.     

The 1st EMBO workshop on PVC bacteria—Planctomycetes–Verrucomicrobia–Chlamydiae superphylum: Exceptions to the bacterial definition?

The PVC superphylum is a phylogenetically supported collection of various related bacterial phyla that comprise unusual characteristics and traits. The ‘PVC’ abbreviation derives from Planctomycetes, Verrucomicrobia and Chlamydiae as members of this superphylum, while additional bacterial phyla are related. There has recently been increasing and exciting interest in the cell biology, physiology and ecology of members of this superphylum, including evolutionary implications of the complex cell organization of some species. It is timely that international researchers in the PVC superphylum field met to discuss these developments. The first meeting entirely dedicated to those bacteria, the EMBO workshop “PVC superphylum: Exceptions to the bacterial definition” was held at the Heidelberg University to catalyze the formation of a vital scientific community supporting PVC-bacterial research. More than 45 investigators from more than 20 countries (PIs, senior scientists and students) attended the meeting and produced a great starting point for future collaborative research. This Special Issue will focus on the EMBO-PVC meeting. This Perspective briefly summarizes the history of PVC-research, focusing on the key findings and provides a brief summary of the meeting with a focus on the major questions that arose during discussion and that might influence the research in the years to come.     

On microrefugia and cryptic refugia

The existence of microrefugia and/or cryptic refugia has been proposed to explain the colonization patterns of temperate continents after the Last Glacial Maximum, as well as to gain an understanding of the present genetic structure of species and their populations. The concepts ‘microrefugia’ and ‘cryptic refugia’ largely overlap but do not fully coincide, which may lead to terminological duplication and eventual semantic misconceptions. Here, after a terminological and conceptual analysis, it is proposed that most situations currently characterized as cryptic refugia can be accommodated within the definition of microrefugia, with one single exception, for which some alternative terms are suggested. Moreover, the concept and definition of cryptic refugia are considered to be more imprecise, perishable and subjective than those of microrefugia, which is the preferred term in the current context.     

Male-like females, mimicry and transvestism in butterflies (Lepidoptera: Papilionidae)

Abstract. When a butterfly species has a polymorphic female, with one of the forms closely resembling the male, it is customary to suppose that this form is ancestral, and that the ‘odd’ forms have arisen later. R. I. Vane-Wright, on the other hand, has suggested that in some species the male-like form may be a ‘transvestite’ female, the ancestral form of the female having been strikingly unlike the male. As later-derived forms are usually, but not always, genetically dominant to ancestral forms, we can make some choice between these hypotheses by discovering the dominance relations of the male-like and the ‘odd’ forms of the female. In the mimetic Papilio aegeus the male-like form is shown to be recessive to the ‘odd’ (mimetic) form, as has essentially been the case in all other butterflies so far investigated. Papilio phorcas is now shown to be the exception: the ‘odd’ (non-mimetic) form is recessive to the male-like form. We conclude that usually the male-like form is ancestral, but that P.phorcas may be an authentic example of ‘transvestism’, or the ‘transfer’ of male epigamic colour to the female of the species. The yellow, male-like pattern of the mimetic Papilio dardanus may be dominant or recessive to the mimetic forms according to the genetic background: largely recessive in Madagascar, and southern and western Africa, dominant to most forms in Ethiopia, and probably dominant to one mimetic form but recessive to the others in Kenya. All female dardanus patterns, both mimetic and yellow, are strongly dominant to both female phorcas patterns in P. dardanus × P. phorcas hybrids (P. ‘nandina’). The simplest explanation of this situation is that the male-like pattern of dardanus is ancestral, and that dominance has become locally reversed in Ethiopia. The dominance relations, and the sex- or autosomal-linkage of two forms can be determined without pedigree-breeding, simply by observing a few offspring each from a large number of wild-caught females.     

A rare case report of polyangiitis overlap syndrome: granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis

Background

Granulomatosis with polyangiitis (GPA) is a systemic ANCA-associated vasculitis characterized by necrotizing granulomatous inflammation and a predilection for the upper and lower respiratory tract. Eosinophilic granulomatosis with polyangiitis (EGPA) is also a systemic ANCA-associated vasculitis, but EGPA is characterized by eosinophilic as well as granulomatous inflammation and is more commonly associated with asthma and eosinophilia.Polyangiitis overlap syndrome is defined as systemic vasculitis that does not fit precisely into a single category of classical vasculitis classification and/or overlaps with more than one category. Several polyangiitis overlap syndromes have been identified, however, there are very few case reports of an overlap syndrome involving both GPA and EGPA in the medical literature.

Case presentation

We conducted a PUBMED literature review using key words ‘granulomatosis with polyangiitis,’ ‘Wegener’s,’ ‘GPA,’ ‘eosinophilic granulomatosis with polyangiitis,’ ‘Churg-Strauss,’ ‘EGPA,’ ‘overlap syndrome,’ ‘Wegener’s with eosinophilia,’ and ‘GPA with eosinophilia’ in English only journals from 1986 to 2017. Relevant case reports and review articles of overlap syndromes of GPA and EGPA were identified. We aim to report a unique case of GPA and EGPA overlap syndrome and review the cases that have been previously described.Between 1986 and 2017, we identified 15 cases that represent an overlap syndrome with compelling features of both GPA and EGPA. Patients ranged in age between 21 and 78. Of those whose gender was identified, 80 % of the patients were female. All cases described involved the lungs, 60 % reported sinus involvement, and more than 50 % displayed renal involvement. An overwhelming majority of patients were positive for c-ANCA and demonstrated eosinophilia (peripheral blood or tissue eosinophilia). A preponderance of the cases described were treated with systemic corticosteroids combined with an immunosuppressive/cytotoxic agents.

Conclusion

To our knowledge, there have been very few cases reported of an overlap syndrome of GPA and EGPA. Identification of patients with a polyangiitis overlap syndrome of GPA and EGPA is imperative as prognosis, longitudinal management and treatment modalities may differ between these entities.

     

A pluralist challenge to “integrative medicine”: Feyerabend and Popper on the cognitive value of alternative medicine

This paper is a critique of ‘integrative medicine’ as an ideal of medical progress on the grounds that it fails to realise the cognitive value of alternative medicine. After a brief account of the cognitive value of alternative medicine, I outline the form of ‘integrative medicine’ defended by the late Stephen Straus, former director of the US National Centre for Complementary and Alternative Medicine. Straus’ account is then considered in the light of Zuzana Parusnikova’s recent criticism of ‘integrative medicine’ and her distinction between ‘cognitive’ and ‘opportunistic’ engagement with alternative medicine. Parusnikova warns that the medical establishment is guilty of ‘dogmatism’ and proposes that one can usefully invoke Karl Popper’s ‘critical rationalism’ as an antidote. Using the example of Straus, I argue that an appeal to Popper is insufficient, on the grounds that ‘integrative medicine’ can class as a form of cognitively-productive, critical engagement. I suggest that Parusnikova’s appeal to Popper should be augmented with Paul Feyerabend’s emphasis upon the role of ‘radical alternatives’ in maximising criticism. ‘Integrative medicine’ fails to maximise criticism because it ‘translates’ alternative medicine into the theories and terminology of allopathic medicine and so erodes its capacity to provide cognitively-valuable ‘radical alternatives’. These claims are then illustrated with a discussion of ‘traditional’ and ‘medical’ acupuncture. I conclude that ‘integrative medicine’ fails to exploit the cognitive value of alternative medicine and so should be rejected as an ideal of medical progress.     

Informal intercropping of legumes with cereals? A re-assessment of clover abundance in ancient Egyptian cereal processing by-product assemblages: archaeobotanical investigations at Khentkawes town,Giza (2300–2100 <Emphasis Type="SmallCaps">bc</Emphasis>)

The possibility that legumes were specifically cultivated as a separate fodder crop in ancient Egypt has been inferred, usually on the basis of abundance of both legume seeds and or dung in charred macro-botanical samples, combined with a lack of wood charcoal; the implication being that a scarcity of wood led to the use of dung as fuel, and that the legumes in the assemblage derive from livestock which had been fed with cultivated fodder. The archaeobotanical remains from excavations at the Old Kingdom ‘Khentkawes town’ (2300–2100 bc) on the Giza plateau in Egypt contained an abundance of legumes, but also much wood charcoal, and preservation of many fragile and ‘green’ seeds and plant parts. This assemblage has led to questioning of the theory of specific fodder cultivation in Pharaonic Egypt. In this article, alternative interpretations of legume-rich assemblages of cereal processing by-products are investigated. Intercropping of legumes with cereals is one of the most widespread and effective methods of improving crop value and security, and fodder/forage quality. Analysis of this assemblage has led to a hypothesis that Trifolium sp. and other ‘weeds’ may well have been viewed as integral plants within ancient Egyptian cereal fields, due to an awareness of the benefits of intercropping legumes with cereals—as opposed to having been specifically cultivated as a monocrop.     

Architecture and assembly of the Gram‐positive cell wall

The bacterial cell wall is a mesh polymer of peptidoglycan – linear glycan strands cross‐linked by flexible peptides – that determines cell shape and provides physical protection. While the glycan strands in thin ‘Gram‐negative’ peptidoglycan are known to run circumferentially around the cell, the architecture of the thicker ‘Gram‐positive’ form remains unclear. Using electron cryotomography, here we show that Bacillus subtilis peptidoglycan is a uniformly dense layer with a textured surface. We further show it rips circumferentially, curls and thickens at free edges, and extends longitudinally when denatured. Molecular dynamics simulations show that only atomic models based on the circumferential topology recapitulate the observed curling and thickening, in support of an ‘inside‐to‐outside’ assembly process. We conclude that instead of being perpendicular to the cell surface or wrapped in coiled cables (two alternative models), the glycan strands in Gram‐positive cell walls run circumferentially around the cell just as they do in Gram‐negative cells. Together with providing insights into the architecture of the ultimate determinant of cell shape, this study is important because Gram‐positive peptidoglycan is an antibiotic target crucial to the viability of several important rod‐shaped pathogens including Bacillus anthracis, Listeria monocytogenes, and Clostridium difficile.     

Spatial pattern in dry grassland communities of the Central Alps and its ecophysiological significance

The spatial pattern of species and microhabitats in a dry grassland mosaic in a Central Alpine valley was studied by a variance/mean analysis. In addition, the water-usage strategies of the dominant species were investigated. A significant correlation between species pattern and microhabitat pattern was found for the grass species. Grasses, with their homorhizal root system, are unable to exploit sources of water in deep rock crevices, and are therefore dependent on the water-storage capacity of the particular soil layer. Dwarf shrubs and succulents (with one exception) are independent of this latter water source. The common chamaephytes exhibit contradictory types of stomatal behaviour.Artemisia alba is characterized by a water-conservation strategy, whereasHelianthemum nummularium spp.obscurum andTeucrium chamaedrys are not. The careful usage of the water reserves byArtemisia alba would seem to represent an adaptation to dry grassland conditions. The other dwarf shrubs, in contrast, with their ‘water-wasting’ strategy, have a root system like that ofArtemisia and are unable to compensate for the higher rate of water loss. Thus, the observed ecophysiological differences cannot be interpreted as being ‘different solutions to the same problem’, as a result of divergent evolution. Two alternative interpretations are: a) the stomatal behaviour of the chamaephytes is a characteristic of their respective genera and which is not particularly adaptive here; b) the dry grasslands studied are the remnants of a former vegetation type, which had a low level of competition.     

A chiton without a foot

Abstract: The palaeoloricate ‘polyplacophorans’ are an extinct paraphyletic group of basal chiton‐like organisms known primarily from their fossilized valves. Their phylogenetic placement remains contentious, but they are likely to include both stem‐group Polyplacophora and stem‐group Aplacophora. Candidates for the latter position include ‘Helminthochiton’thraivensis from the Ordovician of Scotland, which we redescribe here through a combined optical and micro‐CT (XMT) restudy of the type material. The 11 specimens in the type series are all articulated, presenting partial or complete valve series as well as mouldic preservation of the girdle armature; they demonstrate a vermiform body plan. The valves are typically palaeoloricate in aspect, but differ in detail from all existing palaeoloricate genera; we hence erect Phthipodochiton gen. nov. to contain the species. The most notable feature of the fossils is the spicular girdle; this is impersistently preserved, but demonstrably wraps entirely around the ventral surface of the animal, implying that a ‘true’ (i.e. polyplacophoran like) foot was absent, although we do not exclude the possibility of a narrow solenogastre‐like median pedal groove having been present. Phthipodochiton thraivensis presents an apparent mosaic of aplacophoran and polyplacophoran features and as such will inform our understanding of the relationship between these groups of extant molluscs. An inference may also be drawn that at least some other palaeoloricates possessed an ‘armoured aplacophoran’ body plan, in contrast to the ‘limpet‐like’ body plan of extant Polyplacophora.     

Paternalism's Changing Reputation

Research on the relationship between Aborigines and pastoralists in the Northen Territory can be divided into two traditions. A ‘Liberal-managerial’ tradition, represented by the work of Stevens and the Berndts, fails to explore Aborigines' constructs about that relationship. An alternative ‘ethnographic’ tradition has begun to correct this imbalance by using Aborigines' testimony. An interpretation of these materials suggests that Aborigines applied a model of exchange to their dealings with pastoralists and that their capacity to do so has been undermined by the gradual emergence of wage-labour relations in the industry.     

Motor innervation of the supercontracting longitudinal ventro-lateral muscles of the blowfly larva

The gross motor innervation of the abdominal longitudinal ventro-lateral muscles of the larva of Calliphora erythrocephala is described. Two of these muscles, 6A and 7A, are innervated by the same two multiterminally-ending axons, and thus comprise a single motor unit. No difference is found between the axon diameters in the main nerve trunks, but there is a difference where the axons run over the muscle surface. Only the dorsal, inner, surface of the muscle is innervated. Electro-physiological results show two sizes of EPSP: the large fast EPSP presumably corresponds to the thicker axon and the small slow one to the thinner axon. Preliminary work indicates that it is not possible to distinguish between the two axons with electron microscopy; the presynaptic regions possess both ‘classical’ synaptic and ‘neurosecretory’ type vesicles, and have no glial cell covering.