Constraints Shape Cell Function and Morphology by Canalizing the Developmental Path along the Waddington's Landscape

Studies performed in absence of gravitational constraint show that a living system is unable to choose between two different phenotypes, thus leading cells to segregate into different, alternative stable states. This finding demonstrates that the genotype does not determine by itself the phenotype but requires additional, physical constraints to finalize cell differentiation. Constraints belong to two classes: holonomic (independent of the system's dynamical states, as being established by the space-time geometry of the field) and non-holonomic (modified during those biological processes to which they contribute in shaping). This latter kind of “constraints”, in which dynamics works on the constraint to recreate them, have emerged as critical determinants of self-organizing systems, by manifesting a “closure of constraints.” Overall, the constraints act by harnessing the “randomness” represented by the simultaneous presence of equiprobable events restraining the system within one attractor. These results cast doubt on the mainstream scientific concept and call for a better understanding of causation in cell biology.     

Causal reasoning,causal probabilities,and conceptions of causation

The present paper deals with the tools that can be used to represent causation and to reason about it and, specifically, with their diversity. It focuses on so-called “causal probabilities”—that is, probabilities of effects given one of their causes—and critically surveys a recent paper in which Joyce (2010) argues that the values of these probabilities do not depend on one’s conception of causation. I first establish a stronger independence claim: I show that the very definition of causal probabilities is independent of one’s conception of causation. Second, I investigate whether causal probabilities indeed take the same values under their different possible definitions.     

The Skeleton in the Physical Anthropology Closet1

Abstract

The “new” and “newer” concepts of physical anthropology are oriented to biochemical, genetic and evolutionary studies. While theseareneededand welcome concepts, they often slight the basic tools of anthropometry and typology. Also, the new and newer physical anthropology tends to separate biological factors from their cultural contexts. The writer discusses several questions posed by this shift in emphasis and suggests that the lack of a functional approach lessens the effectiveness of both biologically and culturally oriented investigators.     

Predictive landscapes hidden beneath biological cellular automata

To celebrate Hans Frauenfelder’s achievements, we examine energy(-like) “landscapes” for complex living systems. Energy landscapes summarize all possible dynamics of some physical systems. Energy(-like) landscapes can explain some biomolecular processes, including gene expression and, as Frauenfelder showed, protein folding. But energy-like landscapes and existing frameworks like statistical mechanics seem impractical for describing many living systems. Difficulties stem from living systems being high dimensional, nonlinear, and governed by many, tightly coupled constituents that are noisy. The predominant modeling approach is devising differential equations that are tailored to each living system. This ad hoc approach faces the notorious “parameter problem”: models have numerous nonlinear, mathematical functions with unknown parameter values, even for describing just a few intracellular processes. One cannot measure many intracellular parameters or can only measure them as snapshots in time. Another modeling approach uses cellular automata to represent living systems as discrete dynamical systems with binary variables. Quantitative (Hamiltonian-based) rules can dictate cellular automata (e.g., Cellular Potts Model). But numerous biological features, in current practice, are qualitatively described rather than quantitatively (e.g., gene is (highly) expressed or not (highly) expressed). Cellular automata governed by verbal rules are useful representations for living systems and can mitigate the parameter problem. However, they can yield complex dynamics that are difficult to understand because the automata-governing rules are not quantitative and much of the existing mathematical tools and theorems apply to continuous but not discrete dynamical systems. Recent studies found ways to overcome this challenge. These studies either discovered or suggest an existence of predictive “landscapes” whose shapes are described by Lyapunov functions and yield “equations of motion” for a “pseudo-particle.” The pseudo-particle represents the entire cellular lattice and moves on the landscape, thereby giving a low-dimensional representation of the cellular automata dynamics. We outline this promising modeling strategy.

     

Paraphyly,ancestors, and the goals of taxonomy: A botanical defense of cladism

Cronquist (1987) criticizes cladism for its rejection of paraphyletic groups, which he would retain if he feels they are “conceptually useful.” We argue that paraphyletic higher taxa are artificial classes created by taxonomists who wish to emphasize particular characters or phenetic “gaps,” and that formal recognition of such taxa conveys a misleading picture of common ancestry and character evolution. In our view, classifications should accurately reflect the nested hierarchy of monophyletic groups that is the natural outcome of the evolutionary process. Such systems facilitate the study of evolution and provide an efficient summary of character distributions. Paraphyletic groups, such as “prokaryotes,” “green algae,” “bryophytes,” and “gymnosperms,” should be abandoned, as continued recognition of such groups will only serve to retard progress in understanding evolution. Contrary to Cronquist’s (1987) assertions, cladistic theory is not at odds with standard views on speciation and the existence of ancestors. Groups of interbreeding organisms can continue to exist after giving rise to descendant species, and there are several ways in which such groups, whether extant or extinct, can be incorporated into cladistic classification. In contrast, paraphyletic higher taxa are neither cohesive (integrated by gene flow) nor whole, do not serve as ancestors, and are unacceptable in the phylogenetic system. Fossils may be of great value in assessing phylogenetic relationships and are readily accommodated in cladistic classification. Cladistic studies are helping to answer major questions about plant evolution, and we anticipate increased efforts to develop a truly phylogenetic system.     

Ecological Stability: Reality,Misconceptions, and Implications for Risk Assessment

Over a long time frame, an ecological system may not exhibit constancy due to successional and evolutionary changes in the species composing the system. However, over shorter time frames an ecological system exhibits a certain degree of constancy (i.e., varies within defined bounds). Traditionally, ecologists considered this short-term constancy to reflect a “balance of nature,” which was viewed akin to the simple homeostatic dynamics of physiological systems. This is an appealing perspective because the disruption of the system's “balance” (i.e., its ”health“) can be ascertained by comparing the system's current state after the imposition of a perturbation with the societally desired state (i.e., baseline). Recently, ecologists have started to develop a much more complex, and perhaps more realistic, perspective regarding ecosystem dynamics, which does not depend upon homeostasis with a single baseline state. This new view includes stochastic variation, nonlinear dynamics and alternative states, and poses a challenge for assessing environmental “health” and the risk of creating “unhealthy” ecological systems     

Organisational closure in biological organisms

The central aim of this paper consists in arguing that biological organisms realize a specific kind of causal regime that we call "organisational closure"; i.e., a distinct level of causation, operating in addition to physical laws, generated by the action of material structures acting as constraints. We argue that organisational closure constitutes a fundamental property of biological systems since even its minimal instances are likely to possess at least some of the typical features of biological organisation as exhibited by more complex organisms. Yet, while being a necessary condition for biological organization, organisational closure underdetermines, as such, the whole set of requirements that a system has to satisfy in order to be taken as a paradigmatic example of organism. As we suggest, additional properties, as modular templates and control mechanisms via dynamical decoupling between constraints, are required to get the complexity typical of full-fledged biological organisms.     

UCSF ChimeraX: Structure visualization for researchers,educators, and developers

UCSF ChimeraX is the next‐generation interactive visualization program from the Resource for Biocomputing, Visualization, and Informatics (RBVI), following UCSF Chimera. ChimeraX brings (a) significant performance and graphics enhancements; (b) new implementations of Chimera's most highly used tools, many with further improvements; (c) several entirely new analysis features; (d) support for new areas such as virtual reality, light‐sheet microscopy, and medical imaging data; (e) major ease‐of‐use advances, including toolbars with icons to perform actions with a single click, basic “undo” capabilities, and more logical and consistent commands; and (f) an app store for researchers to contribute new tools. ChimeraX includes full user documentation and is free for noncommercial use, with downloads available for Windows, Linux, and macOS from https://www.rbvi.ucsf.edu/chimerax .     

Whose crisis counts? Intersectionality,austerity and the politics of survival

Foregrounding the voices of minority women in England, Scotland and France, Minority Women and Austerity provides a rich and compelling account of austerity’s lived effects. Through its intersectional analyses and historically attendant frame, the book locates minority women’s experiences of austerity not as fundamentally “new” but rather as an extension and sharpening of conditions of “routinized crisis” and inequality. In doing so it compels its readers to ask: whose crisis counts? In this review paper, I summarize the book’s key contributions. In particular, I discuss the book’s theorizations of “political racelessness” to critique the erasure of minority women’s experiences and activism. I reflect on what this means for those researching austerity and its deleterious effects, and for those participating in anti-austerity activism. I end by discussing the analytical tools that the book offers for interrogating the Left’s response to on-going austerity within a post-Brexit Britain.     

Prayer,Silence, and Psychotherapy

A new interpretation of L.S. Vygotsky's “The Tragedy of Hamlet, the Prince of Denmark” and his little-known publication “Traurnye stroki-Den' 9 ava.” An essential question (object) of these texts is the secret of genuine human overcoming of suffering. This is also the main problem of psychotherapy. Vygotsky's answer has both psychological and religious sgnificance: the experience of a tragedy is mediated by prayer. Vygotsky's idea creates the basis for religiously oriented, “synergetic” psychotherapy where the main process will be spiritual, including prayer.     

Concept,Definition, Prevalence,and Host-Interactions of Xenosomes (Cytoplasmic and Nuclear Endosymbionts)1,2

ABSTRACT. In this paper the concept of “xenosome” is greatly expanded from its current usage, which has been based on its application during the past 10 years by Soldo and co-workers solely to certain bacterial invaders of the cytoplasm in species of a single genus of marine scuticociliales. The author proposes that the term now be considered to embrace all DNA-containing, membrane-bounded bodies or organelles—prokaryotic or eukaryotic in original nature—found within the cytoplasm or nucleus of eukaryotic cells of any or all kinds, whether the occupation (“colonization”) is temporary and transient or permanent and stable. Thus, virulent or pathogenically infectious organisms can be included as well as the commonly recognized cell endosymbionts sensu stricto, which are often mutualistic in nature. Of significance, such “normal” cell organelles as plastids, mitochondria, and even nuclei may also be embraced by this expanded definition of xenosome, based on the conjecture that these inclusions might have been “alien” or “foreign” extracellular, independent, free-living organisms in their own past evolutionary histories. The author's enlarged concept and unifying principle allows more meaningful comparative consideration of the numerous and diverse kinds of xenosome-host interrelationships, many of which involve species of protozoa and algae from a large number of the taxonomic groups comprising the kingdom Protista.     

Links between the discovery of primates and anatomical comparisons with humans,the chain of being,our place in nature,and racism

I focus on the crucial links between the discovery of nonhuman primates by Westerners, discussions on our place in nature, the chain of being, racism, and the history of primate comparative anatomy and of so‐called “anatomical human racial studies.” Strikingly, for more than a millennium humans knew more about the internal anatomy of a single monkey species than about that of their own bodies. This is because Galen used monkeys to infer human anatomy, in line with the human‐animal continuity implied by the Greek notion of scala naturae. With the rise of Christianity, nonhuman primates were increasingly seen in a negative way. A more positive view emerged in the 14th century when nonhuman primates were directly studied/seen by Europeans, culminating in Tyson's 1699 work showing that chimps share more gross anatomical similarities with humans than with monkeys. However, the discomfort caused by this human‐chimp similarity then led to a new idea of animal‐human discontinuity, now related not to anatomy but to “civilization”: between Europeans vs. non‐Europeans + other primates. Moreover, Linnaeus' Systema Naturae and the emergence of “anatomical racial studies” influenced by Camper's craniology then led to even more extreme ideas, such as the notion that Europeans were both mentally and morphologically “ideal.” Unfortunately the biased and often incorrect “results” of such studies, combined with ideas based on Darwin's “struggle for survival”, became crucial in propaganda that lead to the rise of eugenics in the end of the 19th/first half of 20th centuries and that culminated in Nazism. Since the 1950s there has been an emphasis on the continuity/unity between all human groups and other primates, in great part influenced by what happened during World War 2. Reviews such as this one are, therefore, particularly necessary to illuminate and guard against attitudes against “the Other” and racist ideologies that are re‐emerging in modern political discourse across the globe.     

HALDANE'S RULE IS EXTENDED TO PLANTS WITH SEX CHROMOSOMES

Haldane's rule is an empirical phenomenon that has been observed in animals with sex chromosomes. The rule states that the heterogametic sex (XY or ZW) will be “absent, rare, or sterile” following hybridization between two species. Despite the near ubiquity of Haldane's rule in animal hybridizations, it has not been documented in organisms other than animals. Here, we show evidence for both rarity and sterility in hybrid male but not female offspring in crosses between three dioecious plant species from the genus Silene with heteromorphic (XY) sex chromosomes. Our results are consistent with Haldane's rule, extending its applicability to plants with sex chromosomes.     

“Words matter.” A Response to Jørgensen's Treatment of Historic Range and Definitions of Reintroduction

According to Jørgensen, the definition of reintroductions is crucial to their proper implementation and she highlights a number of ambiguities in existing definitions, particularly associated with the concept of historic range. We could not agree more and have incorporated her suggested term of “indigenous range” rather than “historic range” into the current revision of the InternationalUnion for the Conservation of Nature (IUCN) Guidelines for Reintroductions and other Conservation Translocations (in preparation by IUCN Species Survival Commission Reintroduction and Invasive Species Specialist Groups). We also agree with Jørgensen's interpretation that reintroductions are not always necessitated by humans causing the extirpation of species. However, we disagree with other aspects of Jørgensen's argument such as the critique of Seddon, the interpretation of previous IUCN guidance documents, and the recommendation that the conservation community “rethink the basic definition of reintroduction” rather than moving toward other translocation‐based interventions. With regard to the latter point, we emphasize that reintroductions are part of a spectrum of translocations and to focus on reintroductions alone would overlook the fact that introductions beyond a species' indigenous range are being attempted. The new revision of the IUCN guidelines incorporates the whole conservation translocation spectrum and aims to avoid the ambiguities of previous definitions highlighted by Jørgensen.