. ‘Shattered into a Multiplicity of Warring Functions’: Synthesis, Disintegration and ‘Distractibility’ 1. Intellectual History Review: Vol. 17, No. 3, pp. 305-326.

In this paper, we compare the mechanisms of protein synthesis and natural selection. We identify three core elements of mechanistic explanation: functional individuation, hierarchical nestedness or decomposition, and organization. These are now well understood elements of mechanistic explanation in fields such as protein synthesis, and widely accepted in the mechanisms literature. But Skipper and Millstein have argued that natural selection is neither decomposable nor organized. This would mean that much of the current mechanisms literature does not apply (...) to the mechanism of natural selection.We take each element of mechanistic explanation in turn. Having appreciated the importance of functional individuation, we show how decomposition and organization should be better understood in these terms. We thereby show that mechanistic explanation by protein synthesis and natural selection are more closely analogous than they appear—both possess all three of these core elements of a mechanism widely recognized in the mechanisms literature. (shrink)

The etiological account of teleological function is beset by several difficulties, which I propose to solve by grafting onto the etiological theory a subordinated goal-contribution clause. This approach enables us to ascribe neither too many teleofunctions nor too few; to give a unitary, one-clause analysis that works just as well for teleological functions derived from Darwinian evolution, as for those derived from human intention; and finally, to save the etiological theory from falsification, by explaining how, in spite of appearances, the (...) theory can allow for evolutionary function loss. (shrink)

Applying mild methods of preparation, part of the ribosomes of rabbit reticulocytes are found in aggregates (later called polyribosomes) of up to six ribosomal units. Upon treatment with RNA-ase, they desintegrate into single ribosomes. The fast-sedimenting aggregates are found to be more active in protein synthesis in terms of incorporation of radioactive amino acids, whereas the single ribosomes are more receptive to stimulation by the artificial messenger RNA poly-U. The findings indicate that the linkage of ribosomes into aggregates is (...) due to the messenger RNA. They support a tape-reading mechanism of protein synthesis whereby growth of the peptide chain is accompanied by shifting the active site of the ribosome from one coding group of nucleotides of the messenger RNA to the next. (shrink)

One distinguishing feature of vertebrate oocyte meiosis is its discontinuity; oocytes are released from their prophase I arrest, usually by hormonal stimulation, only to again halt at metaphase II, where they await fertilization. The product of the c‐mos proto‐oncogene, Mos, is a key regulator of this maturation process. Mos is a serine‐threonine kinase that activates and/or stabilizes maturation‐promoting factor (MPF), the master cell cycle switch, through a pathway that involves the mitogen‐activated protein kinase (MAPK) cascade. Oocytes arrested at prophase I (...) lack detectable levels of Mos, which must be synthesized from a pool of maternal mRNAs for proper maturation. While Mos is necessary throughout maturation in Xenopus, it seems to be required only for meiosis II in the mouse. The translational activation of c‐mos mRNA at specific times during meiosis requires cytoplasmic polyadenylation. Cis‐ and trans‐acting factors for polyadenylation are, therefore, essential elements of maturation. (shrink)

The pathway for initiation of protein synthesis in eukaryotic cells has been defined and refined over the last 25 years using purified components and in vitro reconstituted systems. More recently, powerful genetic analysis in yeast has proved useful in unraveling aspects of translation inherently more difficult to address by strictly biochemical approaches. One area in particular is the functional analysis of multi‐subunit protein factors, termed eukaryotic initiation factors (eIFs), that play an essential role in translation initiation. eIF‐3, the (...) most structurally complex of the eIFs, has until recently eluded this approach. The identification of the yeast GCD10 gene as the structural gene for the ζ subunit of yeast eIF‐3(1) and the analysis of mutant phenotypes has opened the door to the genetic dissection of the eIF‐3 protein complex. (shrink)

There have been two principal paradigms for the formulation of the causal relation--logical implication and functional relationship. In this paper, I present a case for preferring the functional relationship formulation and then discuss how the functional relationship formulation may be implemented in the probabilistic case in a manner analogous to the way others have implemented the logical implication formulation in the probabilistic case. I show how the "local independence" assumption found in many models used in the behavioral (...) and social sciences is a consequence of the functional relation concept of probabilistic causality. I also discuss why causal relations are underdetermined in experience and are to be dealt with pragmatically in a hypothesis-testing framework. (shrink)

This essay discusses the instructional value of mathematical proofs using different interpretations of the analysis cum synthesis method in Apollonius’ Conics as a case study. My argument is informed by Descartes’ complaint about ancient geometers and William Thurston’s discussion on how mathematical understanding is communicated. Three historical frameworks of the analysis/synthesis distinction are used to understand the instructive function of the analysis cum synthesis method: the directional interpretation, the structuralist interpretation, and the phenomenological interpretation. I apply these (...) interpretations to the analysis cum synthesis method in order reveal how the same underlying mathematical activity occurs at different levels of scale: at the level of an individual proof, at the level of a collection of proofs, and at the level of a single line within a proof. On the basis of this investigation, I argue that the instructive value of mathematical proof lies in engendering in the reader the same mathematical activity experienced by the author themselves. (shrink)

In the paper, the formal model of the noetic synthesis functions is presented. Together with the functions of noematic synthesis, they are understood as components of functions of intentional reference, which are meant to be, in turn, formalizations of intentional acts of reference performed in the stream of consciousness. This research perspective allows us to extend the category of speech acts to the category of all intentional acts of reference. The functions of noetic synthesis are understood as (...) composed of the function of noetic intention acting on qualia, noetic moods and noetic modes. The model allows us to explain the phenomenon of autism as having its source in disorders of the noetic synthesis functions. The constructed model is not intended as the faithful reconstruction of the Husserlian conception of noesis. Intuitions of the creator of phenomenology are treated as the only source of inspiration. (shrink)

In the paper, being the second part of the work entitled Noema and Noesis, the formal model of the noematic synthesis functions is presented. Together with functions of noetic synthesis, they are understood as components of functions of intentional reference, which are to be, in turn, formalizations of intentional acts of reference performed in the stream of consciousness. Noemata are understood as mental representations associated with mental worlds. The processes of their synthesis in the mind engage the (...) work of many noematic functions: generating predicative senses, producing noematic cores, and locating noemata in mental worlds (mental spaces). The constructed model is not intended as the faithful reconstruction of the Husserlian conception of noemata. Intuitions of the creator of phenomenology are treated as the only source of inspiration. (shrink)

This book considers some issues common to the philosophical systems of Kant and Husserl. The distinction between Kant's Synthesis and Husserl's Intentionality is the main subject of this book. The theme of the analysis is the variation of the position and essence of the term Intuition - Anschauung in the two systems. In both systems, Intuition has a central significance. In Kant's system it is because of his conception that the structure of knowledge is a synthesis of intuition (...) and reason. In Husserl's system this is because he considered Intuition to be the medium for the discernment of data. Given the structured nature of philosophical systems, these topics cannot be isolated from the systems in which they function, relating them in each case with various paths of investigation and different interpretations of phenomenology. (shrink)

Talk at University of Turin, 'Kant, oltre Kant, May 5th 2023. --- -/- It is useful, while keeping in mind a holistic approach, to concentrate on a common theme in Kant’s text, which it will turn out is the quintessential element of his novel ‘way of thinking’, as he himself put it in preface of the second edition of the Critique of Pure Reason. This common theme is the idea of synthesis, which is what holds together, and is the (...) entryway to, all the other familiar aspects of Kant’s thought: his concept of self-consciousness or how mind is involved in cognition, his ideas about the role of the imagination, his theory of knowledge and his metaphysics of experience, and not unimportantly, its relation to what is probably the most Kantian element here: the categories of the understanding as the first principles of knowledge. But the meaning of synthesis and its role in its various facets, though frequently the subject of discussion in papers and monographs alike, is hardly understood in contemporary Kant scholarship. Most readings of the text of the Deduction, the part in which Kant elucidates his concept of synthesis, exhibit a shallow, mechanical understanding of it. -/- A compounding factor is that synthesis can’t really be understood independently of the other aforementioned elements of Kant’s thought. Grasping the meaning of synthesis implies coming to grips with his concept of self-consciousness and the way both self-consciousness and the categories are intricately and intimately involved. Most interpretations consider these aspects too much as if they were indeed separable faculties or entities that serve separable functions, undercutting an important feature of Kant’s metaphysics: the possibility of a priori unified cognition, for which an indivisible self-legislating subject is responsible. Rather, they are expressions of various aspects of a singular function of the mind as the ground of possible unified knowledge. -/- One striking example of such a superficial reading of the text is the way the relation between figurative synthesis and intellectual synthesis—or in the case of the A-Deduction the threefold synthesis—is standardly interpreted, as if the two are independent or quasi-independent functions of different faculties of the mind, the imagination and the understanding. In this paper, I focus on the relation between figurative and intellectual synthesis, while arguing that failing to understand this properly, indeed the relation between the imagination and the understanding, leads to a vicious regress in the explanation of the ground of knowledge, for which a priori synthesis is specifically designed. In other words, failing to see the intimate relation between the imagination and the understanding, the very identity that lies at their root, risks losing sight of the primary aim of Kant’s thought: the possibility of a priori unified knowledge. (shrink)

In the complex process of the formation of new religious-religious paradigms, the problem of the interrelationship of religious and national is taken as a priority, since the synthesis of these elements influences the realization of religious experience and, in fact, acts as a characteristic feature of its functioning in the Ukrainian Greek Catholicism itself.

It is of fundamental importance to understand how the individual processes of gene expression, transcription, and translation, as well as mRNA and protein stability, act in concert to produce dynamic cellular proteomes. We use the concept of response times to illustrate the relation between degradation processes and responsiveness of the proteome to system changes and to provide supporting experimental evidence: proteins with short response times tend to be more strongly up‐regulated after 1 hour of TNFα stimulation than proteins with longer (...) response times. Furthermore, based on process‐dependent response times, we demonstrate that synthesis and degradation act in concert to enable rapid responses. Finally, by building on a previously published data set quantifying the mammalian gene expression cascade, we speculate on how combinations of stable and unstable mRNAs and proteins may be wired to transcriptional or translational regulation to support gene function. (shrink)

Among biologists and philosophers, there is an ongoing debate over the Modern Synthesis and the Extended Evolutionary Synthesis. Some argue that our current evolutionary biology is in need of (at least) some substantial revision or nontrivial extension, while others maintain that the Modern Synthesis remains the foundational framework for evolutionary biology. It has been widely debated whether the Extended Evolutionary Synthesis provides a more promising framework than the Modern Synthesis. The nature and methodological implications of (...) the Extended Evolutionary Synthesis were also examined. This paper offers an integrated historical and philosophical examination of the debate over the Extended Evolutionary Synthesis. It reviews the development of evolutionary biology of the twentieth century. It argues that there are substantial conceptual and theoretical differences between the Modern Synthesis and the Extended Evolutionary Synthesis, but they are not incommensurable paradigms in the Kuhnian sense. It also argues for a functional approach to the debate over these two frameworks of evolutionary theory. (shrink)

Kant uses terms translatable as ‘synthesis’ and ‘perception’ in different ways in different contexts, which suggests that there are different kinds of synthesis and perception. I propose that there are two main basic functions of perception according to Kant: that of singling out a thing and that of getting perceptually informed about the configuration of the thing’s perceptible features. I argue that the first function is not dependent on the kinds of syntheses Kant analyzes in the Critique of (...) Pure Reason but grounds any such synthesis. I also argue that if singling out a thing is considered to involve synthesis, then the term ‘synthesis’ is identified with a unification of sensory information itself, which is not of much consequence for the transcendental philosopher. The paper also aims to clarify what ‘manifold’ consists in and what the starting point of the ‘synthesis in apprehension’ might be. (shrink)

The primary function of smooth muscle cells is to contract and alter the stiffness or diameter of hollow organs such as blood vessels, the airways and the gastrointestinal and urogenital tracts. In addition to purely structural functions, smooth muscle cells may play important metabolic roles, particularly in various inflammatory responses. In cell culture, these cells have been shown to be metabolically dynamic, synthesizing and secreting extracellular matrix proteins, glycosaminoglycans and a wide variety of cell–cell signaling proteins, such as interleukins, chemokines (...) and peptide growth factors. Secreted cell signaling proteins participate in the inflammatory response of smooth muscle‐containing organs, and some can also stimulate smooth muscle migration, proliferation and contraction. The cellular signaling pathways controlling synthesis of these signaling proteins are similar to those used by cells mediating innate immunity and may contribute to pathogenesis of diverse diseases including atherosclerosis, asthma, inflammatory bowel diseases and preterm labor. Appreciating the role of smooth muscle cells in these diseases may lead to better understanding of the beneficial effects of anti‐inflammatory drugs as well as identification of new targets for anti‐inflammatory therapy. BioEssays 26:646–655, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Insights into the role of sleep in the molecular mechanisms of memory consolidation may come from studies of activity-dependent synaptic plasticity, such as long-term potentiation (LTP). This commentary posits a specific contribution of sleep to LTP stabilization, in which mRNA transported to dendrites during wakefulness is translated during sleep. Brain-derived neurotrophic factor may drive the translation of newly transported and resident mRNA.

BackgroundHealth behavior change is among the top recommendations for improving health of patients with lifestyle-related chronic diseases. An array of behavior change techniques have been developed to support behavior change initiation and maintenance. These BCTs often show limited success when they are not informed by theory, leading to a mismatch between the intention of the BCT and patients’ needs or expectations. Previous studies have identified a number of resources which patients may require to initiate and maintain health behavior change. Indeed, (...) not yet well established is how BCTs address these resources, i.e., the functional mechanisms of BCTs.PurposeProvide a theoretical framework of the functional mechanisms of BCTs for developing and implementing successful interventions for health behavior change.MethodsConceptual review, including literature analysis and synthesis as well as conceptualization of a new model based on the synthesis.ResultsThrough the integration of dual-process models as well as reward and motivation proceeding, i.e., affective, emotional, or intuitive neurobiological cues, into the rational framework of rather linear cognitive or task-related decision progress, we categorize previously identified resources into three distinct sets: external, internal reflective, and internal affective resources. Based on this triad, we classify BCTs according to their functional mechanisms into facilitating, boosting, and nudging. Consequently, we present a simplified Behavior Change Resource Model that is centered on patients’ resources.ConclusionThe model can be applied to develop health behavior change interventions, which promote engagement and empowerment. Future studies should aim at testing the applicability and practicality of the BCRM. (shrink)

‘Smart’ contrast agents (CA) exhibit dynamic and reversible modulation of their relaxivity by specific physiological or biochemical triggers such as changes in pH, Ca2+ concentration or enzymatic activity (1-3). The extracellular concentration of Ca2+ plays important role in physiological and pathological processes in the nervous system. This led to the designing of a chelating system in which relaxivity is influenced as a function of Ca2+ concentration by changing coordination number around the paramagnetic metal ion. We synthesized a novel bifunctional bismacrocycle (...) [Gd-(DO3A-DTPA- DO3A); Fig.] based on DO3A-EA [{4,7-Bis-carboxymethyl-10-(2-aminoethyl)-1,4,7,10-tetraazacyclododec-1-yl}-acetic acid] coupled to DTPA-bis-anhydride via a flexible alkyl spacer to form the.. (shrink)

We discuss two problems for a general scientific understanding of language, sequences and synergies: how language is an intricately sequenced behavior and how language is manifested as a multidimensionally structured behavior. Though both are central in our understanding, we observe that the former tends to be studied more than the latter. We consider very general conditions that hold in human brain evolution and its computational implications, and identify multimodal and multiscale organization as two key characteristics of emerging cognitive function in (...) our species. This suggests that human brains, and cognitive function specifically, became more adept at integrating diverse information sources and operating at multiple levels for linguistic performance. We argue that framing language evolution, learning, and use in terms of synergies suggests new research questions, and it may be a fruitful direction for new developments in theory and modeling of language as an integrated system. (shrink)

Numerous eukaryotic DNA processing enzymes, such as DNA polymerases and ligases, bind the processivity factor PCNA, which acts as a platform to recruit and regulate the binding of enzymes to their DNA substrate. Multiple PCNA‐interacting motifs (PIPs) are present in these enzymes, but their individual structural and functional role has been a matter of debate. Recent cryo‐EM reconstructions of high‐fidelity DNA polymerase Pol δ (Pol δ), translesion synthesis DNA polymerase κ (Pol κ) and Ligase 1 (Lig1) bound to (...) a DNA substrate and PCNA demonstrate that the critical interaction with PCNA involves the internal PIP proximal to the catalytic domain. The ancillary PIPs, located in long disordered regions, are instead invisible in the reconstructions, and appear to function as flexible tethers when the enzymes fall off the DNA. In this review, we discuss the recent structural advancements and propose a functional hierarchy for the PIPs in Pol δ, Pol κ, and Lig1. (shrink)

As the title indicates, this most recent of Hartshorne's works blends doctrinal exposition with analyses of methodological issues. Each of the sixteen chapters can be read as an independent essay, although the entire work is intended as "an essay in systematic metaphysics." The paradox is resolved once we realize that Hartshorne does not separate substantive discussion and the examination of methodological principles--the text exemplifies the principles latent in "creative synthesis" as he understands it. Each chapter takes shape out of (...) a position-matrix in terms of which a number of possible positions on problems of relations, modality, and temporality are exhibited and finally sifted in order to determine the most viable for future philosophic inquiry. Portions of six of the chapters had previously been published, one as early as 1958; the remaining ten appear for the first time in this volume. Although much of the doctrinal content will be familiar to those who have read Hartshorne's earlier works, the clarity and coherence of these essays make it an especially valuable work for students of metaphysics, whether they accept the neoclassical position or not. In the first chapter, "A Philosophy of Shared Creative Experience," Hartshorne presents his case for the inclusive priority of "becoming" over "being"; in the next three chapters, he turns to a more detailed analysis of technical problems in metaphysics--the specification of the domain of metaphysical inquiry, the viability of the notion of inclusive contrast as the heart of "relativity", and the ultimate coincidence of modal and temporal categories as the summit of the analyses of "abstractions". Each of these chapters is an excellent example of Hartshorne's working through "position-matrices"; but for those who are unfamiliar with Hartshorne's work, or for those who desire a less 'naïve' approach to metaphysical inquiry it might be advisable to turn to Chapters V and VI immediately after Chapter I. In these two essays, Hartshorne presents a general exposition of the structure of his system, exposing and defending the conception of relativity which lies at the heart of his system: the triadicity [[sic]] of creative synthesis must be construed relatively, the contrast of relative and absolute being included within the relative member of the contrast. In the succeeding chapters, the difficulties which such a conception must face are explored in detail. Among the difficulties which Hartshorne focuses upon are the possibility of "non-restrictive or necessary existential truths", the psychological reeducation which a conception of the priority of events necessitates, the explanatory power of directed or asymmetrical relations as opposed to non-directed, symmetrical ones, and the critique of the notion of ens realissimum and its substitution by the universal forms of dependence and independence. It is interesting that at various places in this work Hartshorne indicates that the importance of the problem of the relations among contemporaries must be relegated to secondary status in the philosophy of shared creative experience. It becomes increasingly evident that were the author to stress its importance, he should have to turn to a conception of eternal objects functioning relationally or affirm interaction between God and any other individual in strictly simultaneous states. Either move would necessitate a major shift in his methodological principles and substantive doctrines. That he has struggled with the problem of the relations among contemporaries for so long shows his willingness to confront the possibility of such a shift. This is one of the major criteria for evaluating metaphysicians, as Hartshorne notes; in the light of this criterion, Hartshorne's newest work will be judged a significant contribution to metaphysical inquiry.--R. L. C. (shrink)

Daily rhythms in the rate and specificity of protein synthesis occur in most mammalian cells through an interaction between cell‐autonomous circadian regulation and daily cycles of systemic cues. However, the overall protein content of a typical cell changes little over 24 h. For most proteins, translation appears to be coordinated with protein degradation, producing phases of proteomic renewal that maximize energy efficiency while broadly maintaining proteostasis across the solar cycle. We propose that a major function of this temporal compartmentalization—and (...) of circadian rhythmicity in general—is to optimize the energy efficiency of protein synthesis and associated processes such as complex assembly. We further propose that much of this temporal compartmentalization is achieved at the level of translational initiation, such that the translational machinery alternates between distinct translational mechanisms, each using a distinct toolkit of phosphoproteins to preferentially recognize and translate different classes of mRNA. (shrink)

Many areas of science develop by discovering mechanisms and role functions. Cummins' (1975) analysis of role functions-according to which an item's role function is a capacity of that item that appears in an analytic explanation of the capacity of some containing system-captures one important sense of "function" in the biological sciences and elsewhere. Here I synthesize Cummins' account with recent work on mechanisms and causal/mechanical explanation. The synthesis produces an analysis of specifically mechanistic role functions, one that uses the (...) characteristic active, spatial, temporal, and hierarchical organization of mechanisms to add precision and content to Cummins' original suggestion. This synthesis also shows why the discovery of role functions is a scientific achievement. Discovering a role function (i) contributes to the interlevel integration of multilevel mechanisms, and (ii) provides a unique, contextual variety of causal/mechanical explanation. (shrink)

In this chapter I advance a moderately conceptualist interpretation of Kant’s account of the threefold synthesis in the A-Deduction. Often the first version of TD, the A-Deduction, is thought to be less conceptualist than the later B-version from 1787 (e.g. Heidegger 1991, 1995). Certainly, it seems that in the B-Deduction Kant puts more emphasis on the role of the understanding in determining the manifold of representations in intuition than he does in the A-Deduction. It also appears that in the (...) A-Deduction the seemingly pre-conceptual aspects of a priori synthesis, namely those of the synthesis of apprehension and the imagination, are more prominently featured than in the B-Deduction. And the fact that in the A-Deduction judgement does not appear to play any significant role reinforces the view that the A-Deduction is less strongly conceptualist. I believe that Kant is a conceptualist also in the A-Deduction (as much as in the B-Deduction) in the sense that all syntheses, which are expounded in the second section of the A-Deduction, must be seen as involving the categories or the understanding as the seat of the categories. However, despite some apparent strong modal claims regarding apperception in the A-Deduction, I argue that Kant is a moderate conceptualist in the sense that he allows for the real possibility that some representations are apprehended that are not subsumed or subsumable under the categories, or determined or determinable by the understanding as the seat of the categories. Not all representations must be synthesised and hence be conceptualised (by means of the categories), nor are all representations necessarily conceptualisable (by means of the categories). Often it is argued that the application of the categories must be seen as separate from or prior to conceptualisation (that is, employment of concepts in a judgement), so that the categories must be considered to apply to representations at least to the extent that the productive imagination or recognitive synthesis is involved, even if no empirical concepts are applied in an actual judgement. But it is difficult to see how categories can apply outside the context of an actual judgement in which ipso facto empirical concepts are employed, because, after all, categories are nothing but logical functions of judgement (e.g. B143). More in particular, I shall argue for the claims that (1) appearances to the contrary, all three levels of syntheses in the A-Deduction, including the synthesis of recognition, are interdependent and are not to be seen as operating singly or independently of each other, and hence of the categories; (2) ‘mere’ apprehension, or ‘mere’ intuition, is not dependent on the understanding and the application or possible application of the categories; and that (3) ‘mere’ apprehension does not even invoke a priori synthesis of apprehension and hence is as such fully lawless in terms of Kantian a priori laws. In this context, I also address Kant’s argument in the A-Deduction about the role of the imagination in the production of spatial objects and explain his apt use of the example of cinnabar to show that the kind of association that is at issue here concerns the possibility of knowledge, not the possibility of mere association, as is often assumed. (shrink)

This paper analyzes the biosocial origins of ritual by pointing to its significant social and evolutionary functions. Furthermore, it offers a detailed analysis of ethological studies on rituals in non-human species that are considered groundwork for an integrated analysis of rituals in people. Due to the fact that sociological and anthropological studies of rituals were aimed at studying social functions of rituals and rituals as a form of social interaction and neglected the existence of biogenetic models as the basis of (...) ritual behavior, the aim of this paper was to indicate that ritual is not only a product of cultural development but that it has played an adaptive role in the processes of biological and cultural evolution. (shrink)

Explanatory Externalism states that the only adaptive force in evolution is natural selection. Explanatory Externalism is a central thesis of the Modern Evolutionary Synthesis. The etiological theory of natural selected-effect functions also advocates Explanatory Externalism. According to this theory, natural selection is the process responsible for determining the proper natural functions of traits. However, I will point out several challenges to Explanatory Externalism that are proposed primarily by developmental biology and its various subfields. Based on these challenges, this paper (...) will argue why biological functions cannot be fully explained by the selected-effect theory, i.e., that a theory of biological functions must adopt some kind of Explanatory Internalism. At the end of this paper, I will discuss whether or not Explanatory Internalism entails a pluralistic view of biological functions, and how this discussion is related to the different explanations of fit and diversity found in evolutionary biology. (shrink)

Neurosteroid 17 beta-estradiol (E2) is a steroid synthesized de novo in the nervous system that might influence neuronal activity and behavior. Nevertheless, the impact of E2 on the functioning of those neural systems in which it is slightly synthesized is less questioned. The vestibulo-ocular reflex (VOR) adaptation, may provide an ideal arena for investigating this issue. Indeed, E2 modulates cerebellar parallel fiber-Purkinje cell synaptic plasticity that underlies encoding of VOR adaptation. Moreover, aromatase expression in the cerebellum of adult rodents is (...) maintained at very low levels and localized to Purkinje cells. The significance of age-related maintenance of low levels of aromatase expression in the cerebellum on behavior, however, has yet to be explored. Our aim in this study was to determine whether E2 synthesis exerts an effective and persistent modulation of VOR adaptation in adult male rats. To answer this question, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in VOR adaptation using an oral dose (2.5 mg/kg) of the aromatase inhibitor Letrozole in peri-pubertal and post-pubertal male rats. We found that Letrozole acutely impaired gain increases and decreases in VOR adaptation without altering basal ocular-motor performance and that these effects were similar in peri-pubertal and post-pubertal rats. Thus, in adult male rats neurosteroid E2 effectively modulates VOR adaptation in both of the periods studied. These findings imply that the adult cerebellum uses E2 synthesis for modulating motor memory formation and suggest that low and extremely localized E2 production may play a role in adaptive phenomena. (shrink)

A synthesis of the two primary theory structures in Robert Rosen’s relational complexity, relational entailment mapping based on category theory as described by Rosen and Louie, and relational holism based on modeling relations, as described by Kineman, provides an integral foundation for relational complexity theory as a natural science and analytical method. Previous incompatibilities between these theory structures are resolved by re-interpreting Aristotle’s four causes, identifying final and formal causes as relations with context. Category theory is applied to introduce (...) contextual entailment algebra needed to complete the synthesis. The modeling relation is represented as a recursive four-cause hierarchy, which is a unit of both whole and part analysis that relates realized and contextual domains of nature as complementary inverse entailments between structure and function. Context is a non-localized domain of distributed potentials for existence, as contrasted with the realized domain of localized interactive and measurable events. Synthesis is achieved by giving modeling relations an algebraic form in category theory and by expanding relational analysis to include contextual entailments. The revised form of analysis is applied and demonstrated to examine Rosen’s M-R diagram, showing that structure–function relations imply adaptive interaction with the environment, and that contextual relations imply three forms of the M-R entailment corresponding with the generally known three forms of life; Archaea, Bacteria, and Eukaryota, which can be represented by their holon diagrams. The result of this synthesis is a consistent foundation for relational science that should have important implications in many disciplines. (shrink)

A team of US researchers recently reported the design, assembly and in vivo functionality of a synthetic chromosome III (SynIII) for the yeast Saccharomyces cerevisiae. The synthetic chromosome was assembled bottom‐up from DNA oligomers by teams of students working over several years with researchers as the first part of an international synthetic yeast genome project. Embedded into the sequence of the synthetic chromosome are multiple design changes that include a novel in‐built recombination scheme that can be induced to catalyse intra‐chromosomal (...) rearrangements in a variety of different conditions. This system, along with the other synthetic sequence changes, is intended to aid researchers develop a deeper understanding of how genomes function and find new ways to exploit yeast in future biotechnologies. The landmark of the first synthesised designer eukaryote chromosome, and the power of its massively parallel recombination system, provide new perspectives on the future of synthetic biology and genome research. (shrink)

Perceptual representations are either correct or incorrect. Their correctness depends on their content and on the way the world is. Teleosemantics delivers compelling explanations of why our perceptual representations have contents, whereby it assigns the notion of "function" a central explanatory role. The author of this thesis engages in the search for a theory of function suited for this purpose. After a detailed evaluation of the selected effects​ theory and dispositional theories, the author argues that a synthesis is best (...) suited to be used by teleosemantics. (shrink)

What role does non-genetic inheritance play in evolution? In recent work we have independently and collectively argued that the existence and scope of non-genetic inheritance systems, including epigenetic inheritance, niche construction/ecological inheritance, and cultural inheritance—alongside certain other theory revisions—necessitates an extension to the neo-Darwinian Modern Synthesis (MS) in the form of an Extended Evolutionary Synthesis (EES). However, this argument has been challenged on the grounds that non-genetic inheritance systems are exclusively proximate mechanisms that serve the ultimate function of (...) calibrating organisms to stochastic environments. In this paper we defend our claims, pointing out that critics of the EES (1) conflate non-genetic inheritance with early 20th-century notions of soft inheritance; (2) misunderstand the nature of the EES in relation to the MS; (3) confuse individual phenotypic plasticity with trans-generational non-genetic inheritance; (4) fail to address the extensive theoretical and empirical literature which shows that non-genetic inheritance can generate novel targets for selection, create new genetic equilibria that would not exist in the absence of non-genetic inheritance, and generate phenotypic variation that is independent of genetic variation; (5) artificially limit ultimate explanations for traits to gene-based selection, which is unsatisfactory for phenotypic traits that originate and spread via non-genetic inheritance systems; and (6) fail to provide an explanation for biological organization. We conclude by noting ways in which we feel that an overly gene-centric theory of evolution is hindering progress in biology and other sciences. (shrink)

It has been known for 20 years that the ribosomal protein S6 is rapidly phosphorylated when cells are stimulated to grow or divide. Furthermore, numerous studies have documented that there is a strong correlation between increases in S6 phosphorylation and protein synthesis, leading to the idea that S6 phosphorylation is involved in up‐regulating translation. In an attempt to define a mechanism by which S6 phosphorylation exerts translational control, other studies have focused on characterizing the sites of phosphorylation of this (...) protein and its location within the ribosome. Recent data show that S6 is a protein which may have diverse cellular functions and is essential for normal development, and that it may be involved in the translational regulation of a specific class of messages. (shrink)

One foundational question in contemporarybiology is how to `rejoin evolution anddevelopment. The emerging research program(evolutionary developmental biology or`evo-devo) requires a meshing of disciplines,concepts, and explanations that have beendeveloped largely in independence over the pastcentury. In the attempt to comprehend thepresent separation between evolution anddevelopment much attention has been paid to thesplit between genetics and embryology in theearly part of the 20th century with itscodification in the exclusion of embryologyfrom the Modern Synthesis. This encourages acharacterization of evolutionary developmentalbiology as the (...) marriage of evolutionary theoryand embryology via developmental genetics. Butthere remains a largely untold story about thesignificance of morphology and comparativeanatomy (also minimized in the ModernSynthesis). Functional and evolutionarymorphology are critical for understanding thedevelopment of a concept central toevolutionary developmental biology,evolutionary innovation. Highlighting thediscipline of morphology and the concepts ofinnovation and novelty provides an alternativeway of conceptualizing the `evo and the `devoto be synthesized. (shrink)

It may be that eukaryotic nuclei contain a collection of operationally independent units (genes), each controlled through its interactions with soluble protein factors which diffuse at random throughout the nucleoplasmic space. Alternatively, nuclei might be organized in such a sophisticated fashion that specific genes, occupy distinct sites and that spatially ordered RNA synthesis, processing and transport delivers mature RNAs to predestined sites in the cytoplasm.Different fields of research support each of these extreme views. Molecular biologists inspecting the precise details (...) of specific interactions, usually in vitro, inevitably favour the former, while cell biologists working with far more complicated systems generally assume that more elaborate arrangements exist. In considering the importance of nuclear architecture, I have attempted to relate a collection of experiments each of which intimates some close relationship between structural aspects of chromatin organization and the precise mechanisms underlying nuclear function. I will argue that higherorder structures are crucial for achieving the observed efficiency and coordination of many nuclear processes. (shrink)

Evolutionary epistemology has experienced a continuous rise over the last decades. Important new theoretical considerations and novel empirical findings have been integrated into the existing framework. In this paper, I would like to suggest three lines of research that I believe will significantly contribute to further advance EE: ontogenetic considerations, key ideas from cognitive biology, and the framework of the Extended Evolutionary Synthesis. EE, in particular the program of the evolution of epistemological mechanisms, seeks to provide a phylogenetic account (...) of the generation of cognitive processes underlying knowledge creation. Traditionally, EE and EEM have been oriented towards an account of evolutionary theory that mainly drew from the tenets of the Modern Synthesis. The Modern Synthesis largely dismisses ontogenetic processes and considers them irrelevant for evolutionary explanations. If anything, the role of development in evolution is believed to be that of a constraint. There is, however, ample evidence for a tight intertwinement of developmental and evolutionary processes. Organisms employ their cognitive apparatus to interact with the environment in order to achieve a fully functioning perceptual and cognitive nervous system. Also, ontogeny provides generative potentials to enable variations that natural selection can act upon. EEM’s agenda may, therefore, strongly benefit from bringing together ontogenetic and phylogenetic approaches. To grapple with this challenge, an alternative vision of the evolutionary theory termed Extended Evolutionary Synthesis could be used. This extended evolutionary theory explores relationships between the processes of individual development and phenotypic change during evolution and can provide a more suitable framework for EEM to draw from. In recent years, cognitive biology has gained momentum as an independent research field. Cognitive biology builds on the concepts of EEM and understands knowledge as a biogenic phenomenon. Its main objective is also the formulation of substantiated interrelations between cognition and evolution but it focuses on cognitive functionality at all levels of biological organization. It thus employs a “vertical” approach that encompasses nested hierarchies which span from single molecules, cells, and tissues to the organismal level, communities, and societies. In contrast to cognitive biology, EEM is here understood to adopt a “horizontal” approach that focuses on phylogenetic explanations of cognition and knowledge acquisition. Linking EEM with the key ideas of cognitive biology could make EEM’s research program stronger as it can more easily accommodate phylogenetic and ontogenetic questions within a hierarchical, multilevel perspective. This is of particular importance for a more comprehensive account of cognition since living systems are subject to context-dependent causal influences from different organizational levels. In addition to EEM, there is a second program of EE. This program has been labeled evolutionary epistemology of theories and understands the increase in human knowledge, such as scientific theories, as naturalistic accounts of evolution. Both, EEM and EET initially drew from the core concepts of the Modern Synthesis. Several scholars have severely criticized the analogies made between EET and the Neo-Darwinian key processes of evolution. In particular processes of random mutation, the rate of variation, natural selection as the unique driving force, and the adaptationist agenda are believed to reveal disanalogies. In contrast to the Modern Synthesis, the Extended Evolutionary Synthesis not only recognizes developmental processes but also ecological interactions and systems dynamics as well as social and cultural evolutionary reciprocity as important evolutionary processes. Concepts of the Extended Evolutionary Synthesis are therefore expected to be more fruitful for re-conceptualizing parallels between scientific theorizing and biological evolution. (shrink)

For the current, turning point in the history of Ukraine characterized by the desire of ideologues of different confessions to speak from the standpoint of the global vision of the world, the inclusion in the public consciousness of the ideological function of religion, through which the religious interpretation of the relationship "man - the world" is revealed. To achieve this they seek, in particular, through the involvement in theological outlook of theological interpretations of the achievements of the combined science, which (...) supposedly only in such a way acquire perfection and true meaning. (shrink)

Since the 1940s, microbiologists, biochemists and population geneticists have experimented with the genetic mechanisms of microorganisms in order to investigate evolutionary processes. These evolutionary studies of bacteria and other microorganisms gained some recognition from the standard-bearers of the modern synthesis of evolutionary biology, especially Theodosius Dobzhansky and Ledyard Stebbins. A further period of post-synthesis bacterial evolutionary research occurred between the 1950s and 1980s. These experimental analyses focused on the evolution of population and genetic structure, the adaptive gain of (...) new functions, and the evolutionary consequences of competition dynamics. This large body of research aimed to make evolutionary theory testable and predictive, by giving it mechanistic underpinnings. Although evolutionary microbiologists promoted bacterial experiments as methodologically advantageous and a source of general insight into evolution, they also acknowledged the biological differences of bacteria. My historical overview concludes with reflections on what bacterial evolutionary research achieved in this period, and its implications for the still-developing modern synthesis. (shrink)

Advocates of Extended Evolutionary Synthesis claim that the gene-centric framework of Modern Synthesis (MS) inadequately addresses epigenetics and extended heredity. Historically, epigenetic inheritance relates to Lamarck's inheritance of acquired characters, which was widely accepted before the dominance of MS. In this talk, I argue that the challenge posed by epigenetic inheritance to the gene-centric view arises partly from the ambiguous use of "gene," "phenotype," and "environment" concepts. A functional analysis of the gene concept played in the formal (...) evolutionary models shows that the gene can include materials like exogenes, demonstrating the flexibility of evolutionary theory beyond the verbal MS. Properly understanding the evolutionary gene concept reveals that incorporating epigenetic inheritance does not demand a radical revision of the contemporary evolutionary theory. (shrink)

DNA replication stress threatens ordinary DNA synthesis. The evolutionarily conserved DNA replication stress response pathway involves sensor kinase Mec1/ATR, adaptor protein Mrc1/Claspin, and effector kinase Rad53/Chk1, which spurs a host of changes to stabilize replication forks and maintain genome integrity. DNA replication forks consist of largely distinct sets of proteins at leading and lagging strands that function autonomously in DNA synthesis in vitro. In this article, we discuss eSPAN and BrdU‐IP‐ssSeq, strand‐specific sequencing technologies that permit analysis of protein (...) localization and DNA synthesis at individual strands in budding yeast. Using these approaches, we show that under replication stress Rad53 stalls DNA synthesis on both leading and lagging strands. On lagging strands, it stimulates PCNA unloading, and on leading strands, it attenuates the replication function of Mrc1‐Tof1. We propose that in doing so, Rad53 couples leading and lagging strand DNA synthesis during replication stress, thereby preventing the emergence of harmful ssDNA. (shrink)

This lecture will deal with the heuristic power of the deductive method and its contributions to the scientific task of finding new knowledge. I will argue for a new reading of the term 'deductive method.' It will be presented as an architectural scheme for the reconstruction of the processes of gaining reliable scientific knowledge. This scheme combines the activities of doing science with the activities of presenting scientific results. It combines the heuristic and the deductive side of science. The heuristic (...) side is represented, e.g., by the creative methods to find the 'best' hypotheses, to design experimental systems for empirical research in order to formulate general laws, or to create axiomatic systems. The other side consists of the production of deductive knowledge. This combination leads to a clear hierarchy: the heuristic side provides the basic presuppositions from which the deductive side takes off. The former is used to make deductions possible. The deductive method can be presented as an analysis-synthesis scheme as it can be found, e.g., in the tradition of Kant, Jakob Friedrich Fries, and Leonard Nelson. Nelson's critical philosophy can be seen as a key for understanding the philosophy behind David Hilbert's early axiomatic method. This axiomatic method is usually restricted to a non-philosophical approach to pure mathematics. But Hilbert was not an exclusive formalist; he proposed a mathesis universalis in the Cartesian-Leibnizian sense according to which mathematics is the syntactical tool for a general philosophy of science, applicable to all scientific disciplines. In this function, mathematics takes its problems from the sciences. Hilbert did not deny that mathematics should play a role in explaining the world. The analysis-synthesis scheme helps to provide a consistent interpretation of these two sides of Hilbert's attitude towards his working field. (shrink)

"These notes are about the process of design: the process of inventing things which display new physical order, organization, form, in response to function." This book, opening with these words, presents an entirely new theory of the process of design. In the first part of the book, Christopher Alexander discusses the process by which a form is adapted to the context of human needs and demands that has called it into being. He shows that such an adaptive process will be (...) successful only if it proceeds piecemeal instead of all at once. It is for this reason that forms from traditional un-self-conscious cultures, molded not by designers but by the slow pattern of changes within tradition, are so beautifully organized and adapted. When the designer, in our own self-conscious culture, is called on to create a form that is adapted to its context he is unsuccessful, because the preconceived categories out of which he builds his picture of the problem do not correspond to the inherent components of the problem, and therefore lead only to the arbitrariness, willfulness, and lack of understanding which plague the design of modern buildings and modern cities. In the second part, Mr. Alexander presents a method by which the designer may bring his full creative imagination into play, and yet avoid the traps of irrelevant preconception. He shows that, whenever a problem is stated, it is possible to ignore existing concepts and to create new concepts, out of the structure of the problem itself, which do correspond correctly to what he calls the subsystems of the adaptive process. By treating each of these subsystems as a separate subproblem, the designer can translate the new concepts into form. The form, because of the process, will be well-adapted to its context, non-arbitrary, and correct. The mathematics underlying this method, based mainly on set theory, is fully developed in a long appendix. Another appendix demonstrates the application of the method to the design of an Indian village. (shrink)

In this article, I argue that the relationship between place and self can be accounted for by recent theoretical work on autobiographical memory. The link between place and self is conceptualized as a transitory mental representation that emerges as a “place of mine” (personal autobiographical experience) from a “place” (declarative knowledge). The function of “place of mine” is to guide personal memory and self-knowing consciousness of periods of our lives. I combine inquiries of memory, self, and place in a triadic (...) relationship, a synthesis, suggesting a conceptual model for the phenomenon of place-related self as a sub-system of the self. This is formed by a causal progression from a physical place across time via emotional and cognitive bonds, components of the autobiographical information grounding the self, apportioned across declarative memory. Finally, using the methods of factor analysis and structural equation modeling, I show that the proposed model accounts for previous and new data on place-related identity. (shrink)

The cognitive and behavioral functions of the frontal lobes have been of great interest to neuroscientists, neurologists, psychologists and psychiatrists. Recent technical advances have made it possible to trace their neuroanatomical connections more precisely and to conduct evoked potential and neuroimaging studies in patients. This book presents a broad and authoritative synthesis of research progress in this field. It encompasses neuroanatomical studies; experiments involving temporal organization and working memory tasks in non-human primates; clinical studies of patients following frontal lobe (...) excisions for intractable epilepsy; metabolic imaging in schizophrenia and affective disorder; neurobehavioral studies of patients with dementia, frontal lobe tumors, and head injuries; magnetic resonance imaging methods for studying human frontal lobe anatomy; theoretical approaches to describing frontal lobe functions; and rehabilitation of patients with frontal lobe damage including their core problem of diminished awareness. Written by a distinguished group of neuroscientists, psychologists and clinicians, Frontal Lobe Function and Dysfunction provides the best current source of information on this region of the brain and its role in cognition, behavior and clinical disorders. (shrink)

The fungal cell wall is a dynamic structure that protects the cell from changes in osmotic pressure and other environmental stresses, while allowing the fungal cell to interact with its environment. The structure and biosynthesis of a fungal cell wall is unique to the fungi, and is therefore an excellent target for the development of anti‐fungal drugs. The structure of the fungal cell wall and the drugs that target its biosynthesis are reviewed. Based on studies in a number of fungi, (...) the cell wall has been shown to be primarily composed of chitin, glucans, mannans and glycoproteins. The biosynthesis of the various components of the fungal cell wall and the importance of the components in the formation of a functional cell wall, as revealed through mutational analyses, are discussed. There is strong evidence that the chitin, glucans and glycoproteins are covalently cross‐linked together and that the cross‐linking is a dynamic process that occurs extracellularly. BioEssays 28: 799–808, 2006. © 2006 Wiley Periodicals, Inc. (shrink)