How does the genetic code navigate through the mind-boggling list of alternatives? This brief article gives a clue.

Living organisms are caught between a hammer and an anvil, evolutionarily speaking. On the one hand, they need to buffer the influences of genetic mutations and environmental stresses if they are to develop normally and maintain a coherent and functional form. On the other, stabiliz- ing one’s development too much may mean not being able to respond at all to changes in the environment and starting down the primrose path to extinction. On page 618 of this issue, Queitsch et al.1 (...) propose that, in plants, the balance between stability and the potential for change is made possible in part through a protein involved in ‘heat- shock responses’ in a wide variety of species, from plants to insects. (shrink)

This book (in German) on "Physics, life and mind" is on the physical foundations of modern biology. The basic features of living systems, reproduction, mutation and metabolism, can be explained in terms of molecular processes involving nucleic acids as genetic material, and proteins as catalysts. The generation of structure and form in each generation results from spatiotemporal gene regulation in conjunction with the de novo formation of spatial order in which interplays of activation and inhibition play a crucial part. (...) Brain functions can be understood in terms of information processing in neural networks. Fundamental limitations of explanations of biological phenomena on the basis of physics are expected for the relation between neural and mental states, which may not be fully decodable by finite procedures. A complete algorithmic theory of the human mind encompassing all, including self-referential, aspects appears to be impossible even in principle, not only in practice. The range and limitations of explanations of life on the basis of physical laws and processes reflect the scope and limits of science in general. In contrast to the notions in circulation in the 19th century, modern science is open at the metatheoretical level to different philosophical, cultural and religious interpretations of man and the universe. -/- . (shrink)

Recent successes of systems biology clarified that biological functionality is multilevel. We point out that this fact makes it necessary to revise popular views about macromolecular functions and distinguish between local, physico-chemical and global, biological functions. Our analysis shows that physico-chemical functions are merely tools of biological functionality. This result sheds new light on the origin of cellular life, indicating that in evolutionary history, assignment of biological functions to cellular ingredients plays a crucial role. In this wider picture, even if (...) aggregation of chance mutations of replicator molecules and spontaneously self-assembled proteins led to the formation of a system identical with a living cell in all physical respects but devoid of biological functions, it would remain an inanimate physical system, a pseudo-cell or a zombie-cell but not a viable cell. In the origin of life scenarios, a fundamental circularity arises, since if cells are the minimal units of life, it is apparent that assignments of cellular functions require the presence of cells and vice versa. Resolution of this dilemma requires distinguishing between physico-chemical and biological symbols as well as between physico-chemical and biological information. Our analysis of the concepts of symbol, rule and code suggests that they all rely implicitly on biological laws or principles. We show that the problem is how to establish physico-chemically arbitrary rules assigning biological functions without the presence of living organisms. We propose a solution to that problem with the help of a generalized action principle and biological harnessing of quantum uncertainties. By our proposal, biology is an autonomous science having its own fundamental principle. The biological principle ought not to be regarded as an emergent phenomenon. It can guide chemical evolution towards the biological one, progressively assigning greater complexity and functionality to macromolecules and systems of macromolecules at all levels of organization. This solution explains some perplexing facts and posits a new context for thinking about the problems of the origin of life and mind. (shrink)

The concepts of the origin of the genetic code and the definitions of life changed dramatically after the RNA world hypothesis. Main narratives in molecular biology and genetics such as the “central dogma,” “one gene one protein” and “non-coding DNA is junk” were falsified meanwhile. RNA moved from the transition intermediate molecule into centre stage. Additionally the abundance of empirical data concerning nonrandom genetic change operators such as the variety of mobile genetic elements, persistent viruses and defectives do not (...) fit with the dominant narrative of error replication events (mutations) as being the main driving forces creating genetic novelty and diversity. The reductionistic and mechanistic views on physico-chemical properties of the genetic code are no longer convincing as appropriate descriptions of the abundance of non-random genetic content operators which are active in natural genetic engineering and natural genome editing. (shrink)

Molecular clocks based upon amino acid sequences in proteins have played a major role in the clarification of evolutionary phylogenies. Creationist criticisms of these methods sometimes rely upon data that might initially seem to be paradoxical. For example, human cytochrome c differs from that of an alligator by 13 amino acids but differs by 14 amino acids from a much more closely related primate, Otolemur garnettii. The apparent anomaly is resolved by taking into consideration the variable substitution rate of cytochrome (...) c, particularly among primates. This paper traces some of the history of extensive research into the topic of rate heterogeneity in cytochrome c including data from cytochrome c pseudogenes. (shrink)

The Protein Ontology (PRO) provides a formal, logically-based classification of specific protein classes including structured representations of protein isoforms, variants and modified forms. Initially focused on proteins found in human, mouse and Escherichia coli, PRO now includes representations of protein complexes. The PRO Consortium works in concert with the developers of other biomedical ontologies and protein knowledge bases to provide the ability to formally organize and integrate representations of precise protein forms so as to (...) enhance accessibility to results of protein research. PRO (http://pir.georgetown.edu/pro) is part of the Open Biomedical Ontologies (OBO) Foundry. (shrink)

This research note challenges the idea that Random Somatic Mutations are entirely random, highlighting their non-equiprobable nature and their influence on evolution, involution, or indeterminacy. It recalls the Neutrosophic Theory of Evolution, extending Darwin’s theory, and emphasizes the importance of distinguishing between different senses of ‘random mutation’ in evolutionary theory.

The Protein Ontology (PRO) web resource provides an integrative framework for protein-centric exploration and enables specific and precise annotation of proteins and protein complexes based on PRO. Functionalities include: browsing, searching and retrieving, terms, displaying selected terms in OBO or OWL format, and supporting URIs. In addition, the PRO website offers multiple ways for the user to request, submit, or modify terms and/or annotation. We will demonstrate the use of these tools for protein research and annotation.

The Protein Ontology (PRO; http://proconsortium.org) formally defines protein entities and explicitly represents their major forms and interrelations. Protein entities represented in PRO corresponding to single amino acid chains are categorized by level of specificity into family, gene, sequence and modification metaclasses, and there is a separate metaclass for protein complexes. All metaclasses also have organism-specific derivatives. PRO complements established sequence databases such as UniProtKB, and interoperates with other biomedical and biological ontologies such as the Gene Ontology (...) (GO). PRO relates to UniProtKB in that PRO’s organism-specific classes of proteins encoded by a specific gene correspond to entities documented in UniProtKB entries. PRO relates to the GO in that PRO’s representations of organism-specific protein complexes are subclasses of the organism-agnostic protein complex terms in the GO Cellular Component Ontology. The past few years have seen growth and changes to the PRO, as well as new points of access to the data and new applications of PRO in immunology and proteomics. Here we describe some of these developments. (shrink)

This article offers an explanation of perhaps Wittgenstein’s strangest and least intuitive thesis – the semantical mutation thesis – according to which one can never answer a mathematical conjecture because the new proof alters the very meanings of the terms involved in the original question. Instead of basing our justification on the distinction between mere calculation and proofs of isolated propositions, characteristic of Wittgenstein’s intermediary period, we generalize it to include conjectures involving effective procedures as well.

Biomedical ontologies are emerging as critical tools in genomic and proteomic research where complex data in disparate resources need to be integrated. A number of ontologies exist that describe the properties that can be attributed to proteins; for example, protein functions are described by Gene Ontology, while human diseases are described by Disease Ontology. There is, however, a gap in the current set of ontologies—one that describes the protein entities themselves and their relationships. We have designed a (...) class='Hi'>PRotein Ontology (PRO) to facilitate protein annotation and to guide new experiments. The components of PRO extend from the classification of proteins on the basis of evolutionary relationships to the representation of the multiple protein forms of a gene (products generated by genetic variation, alternative splicing, proteolytic cleavage, and other post-translational modification). PRO will allow the specification of relationships between PRO, GO and other OBO Foundry ontologies. Here we describe the initial development of PRO, illustrated using human proteins from the TGF-beta signaling pathway. (shrink)

The Protein Ontology (PRO; http://purl.obolibrary.org/obo/pr) formally defines and describes taxon-specific and taxon-neutral protein-related entities in three major areas: proteins related by evolution; proteins produced from a given gene; and protein-containing complexes. PRO thus serves as a tool for referencing protein entities at any level of specificity. To enhance this ability, and to facilitate the comparison of such entities described in different resources, we developed a standardized representation of proteoforms using UniProtKB as a sequence reference and PSI-MOD (...) as a post-translational modification reference. We illustrate its use in facilitating an alignment between PRO and Reactome protein entities. We also address issues of scalability, describing our first steps into the use of text mining to identify protein-related entities, the large-scale import of proteoform information from expert curated resources, and our ability to dynamically generate PRO terms. Web views for individual terms are now more informative about closely-related terms, including for example an interactive multiple sequence alignment. Finally, we describe recent improvement in semantic utility, with PRO now represented in OWL and as a SPARQL endpoint. These developments will further support the anticipated growth of PRO and facilitate discoverability of and allow aggregation of data relating to protein entities. (shrink)

Representing species-specific proteins and protein complexes in ontologies that are both human and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and (...) modified forms. Because proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. (shrink)

The Protein Ontology (PRO) is designed as a formal and principled Open Biomedical Ontologies (OBO) Foundry ontology for proteins. The components of PRO extend from a classification of proteins on the basis of evolutionary relationships at the homeomorphic level to the representation of the multiple protein forms of a gene, including those resulting from alternative splicing, cleavage and/or posttranslational modifications. Focusing specifically on the TGF-beta signaling proteins, we describe the building, curation, usage and dissemination of PRO. PRO provides (...) a framework for the formal representation of protein classes and protein forms in the OBO Foundry. It is designed to enable data retrieval and integration and machine reasoning at the molecular level of proteins, thereby facilitating cross-species comparisons, pathway analysis, disease modeling and the generation of new hypotheses. (shrink)

It is widely understood that protein functions can be exhaustively described in terms of no single parameter, whether this be amino acid sequence or the three-dimensional structure of the underlying protein molecule. This means that a number of different attributes must be used to create an ontology of protein functions. Certainly much of the required information is already stored in databases such as Swiss-Prot, Protein Data Bank, SCOP and MIPS. But the latter have been developed for (...) different purposes and the separate data-structures which they employ are not conducive to the needed data integration. When we attempt to classify the entities in the domain of proteins, we find ourselves faced with a number of cross-cutting principles of classification. Our question here is: how can we bring together these separate taxonomies in order to describe protein functions? Our proposed answer is: via a careful top-level ontological analysis of the relevant principles of classification, combined with a new framework for the simultaneous manipulation of classifications constructed for different purposes. (shrink)

Biochemical kinds such as proteins pose interesting problems for philosophers of science, as they can be studied from the points of view of both biology and chemistry. The relationship between the biological functions of biochemical kinds and the microstructures that they are related to is the key question. This leads us to a more general discussion about ontological reductionism, microstructuralism, and multiple realization at the biology-chemistry interface. On the face of it, biochemical kinds seem to pose a challenge for ontological (...) reductionism and hence motivate a dual theory of chemical and biological kinds, a type of pluralism about natural kinds. But it will be argued that the challenge, which is based on multiple realization, can be addressed. The upshot is that there are reasonable prospects for ontological reductionism about biochemical kinds, which corroborates natural kind monism. (shrink)

The short paper introduces the concept of possible branches of double-stranded DNA (later sometimes called palindromes): Certain sequences of nucleotides may be followed, after a short unpaired stretch, by a complementary sequence in reversed order, such that each DNA strand can fold back on itself, and the DNA assumes a cruciform or tree-like structure. This is postulated to interact with regulatory proteins. -/- .

Purpose: The purpose of the discussion is to call for an experimental trial in order to optimize the sociology of knowledge in the astronomical and cosmological sciences from a cognitive science and developmental psychology perspective. The potential of such experimental trial may also correlate developmental psychology with cosmology and astrophysics, therefore, contribute to public health from an astrobiological perspective. -/- Method: The discussion adopts a philosophizing method for the multidisciplinary and trans-disciplinary proposal, with the hypothesis that proton decay in cosmology (...) is correlative to neuronal development in human biochemistry. The method adopts a humanitarian paradigm of pragmatism in natural mutation from cosmic changes, in an exploratory heuristics for hydro-sampling of mutational potentials from environmental factors in cosmological large-scale structure. -/- Result: With an initial assessment on existing technologies, the potentials of the big data trend in astronomy and astrophysics can be applied to data analysis with solid-state electrolytes in sensor baselines to nuclear medicine methods. (shrink)

Protein α-helices provide an ordered biological environment that is conducive to soliton-assisted energy transport. The nonlinear interaction between amide I excitons and phonon deformations induced in the hydrogen-bonded lattice of peptide groups leads to self-trapping of the amide I energy, thereby creating a localized quasiparticle (soliton) that persists at zero temperature. The presence of thermal noise, however, could destabilize the protein soliton and dissipate its energy within a finite lifetime. In this work, we have computationally solved the system (...) of stochastic differential equations that govern the quantum dynamics of protein solitons at physiological temperature, T=310 K, for either a single isolated α-helix spine of hydrogen bonded peptide groups or the full protein α-helix comprised of three parallel α-helix spines. The simulated stochastic dynamics revealed that although the thermal noise is detrimental for the single isolated α-helix spine, the cooperative action of three amide I exciton quanta in the full protein α-helix ensures soliton lifetime of over 30 ps, during which the amide I energy could be transported along the entire extent of an 18-nm-long α-helix. Thus, macromolecular protein complexes, which are built up of protein α-helices could harness soliton-assisted energy transport at physiological temperature. Because the hydrolysis of a single adenosine triphosphate molecule is able to initiate three amide I exciton quanta, it is feasible that multiquantal protein solitons subserve a variety of specialized physiological functions in living systems. (shrink)

The objective of this article is to try to elucidate Wittgenstein’s ex-travagant thesis that each and every mathematical advancement involves some “semantical mutation”, i.e., some alteration of the very meanings of the terms involved. To do that we will argue in favor of the idea of a “modal incompati-bility” between the concepts involved, as they were prior to the advancement, and what they become after the new result was obtained. We will also argue that the adoption of this thesis (...) profoundly alters the traditional way of con-struing the idea of “progress” in mathematics. (shrink)

Mitchell & Gronenborn propose that we account for the presence of multiple models of protein structure, each produced in different contexts, through the framework of integrative pluralism. I argue that two interpretations of this framework are available, neither of which captures the relationship between a model and the protein structure it represents or between multiple models of protein structure. Further, it inclines us toward concluding prematurely that models of protein structure are right in their contexts and (...) makes extrapolation of findings from one context to another seem unwarranted. Instead, protein structure determination ought to be understood as modestly monistic. There is one model for every protein in each physicochemical context, and models of the same protein produced in different contexts are compatible with one another. ‘Integrating’ multiple models amounts to extrapolating from one context to another; this is possible because the effect of context on protein folding is relatively weak and predictable. Modest monism better describes the practice of protein structure determination than integrative pluralism and enables greater attention to how context affects protein folding. (shrink)

Objective: To determine the frequency and type of food allergy in patients having atopic dermatitis and to show the presence of mutations genetically. -/- Methods: Patients diagnosed as having atopic dermatitis according to the Hanifin Rajka criteria were evaluated retrospectively. Eosinophils, total immunoglobin E, milk-specific immunoglobulin E, egg-specific immunoglobulin E, wheat-specific immunoglobulin E, and filaggrin gene mutation results were recorded. Nutrient elimination was performed for 1 month in patients who were thought to have food allergy owing to skin prick (...) test and milk-specific immunoglobulin E results. The diagnosis was confirmed through a food loading test for the patients who benefited from the elimination. -/- Results: Of the 66 patients included in the study, 42 (63.63%) were male. Food allergies were detected in 40 patients (60.6%). According to the Scoring of Atopic Dermatitis index, 9 out of 16 patients aged 40 years and over had food allergy and 31 out of 50 patients aged under 40 years had food allergy. There was no significant difference between the groups (P=.56). All patients included in the study were examined for filaggrin. Only 1 patient with a Scoring of Atopic Dermatitis index below 40 and milk allergy was found to have p.R501 * and c.2282-2285delCAGT mutations. -/- Conclusion: Atopic dermatitis food allergy was found to be 60.6%. The most common improvement was egg allergy and egg elimination. There was no difference between atopic dermatitis severity and food allergy and laboratory tests. Severe atopic dermatitis was found to be 24.2%. (shrink)

In the beginning of the 20th century the groundbreaking work of Ramon y Cajal firmly established the neuron doctrine, according to which neurons are the basic structural and functional units of the nervous system. Von Weldeyer coined the term “neuron” in 1891, but the huge leap forward in neuroscience was due to Cajal’s meticulous microscopic observations of brain sections stained with an improved version of Golgi’s la reazione nera (black reaction). The latter improvement of Golgi’s technique made it possible to (...) visualize the arborizations of single neurons that were “colored brownish black even to their finest branchlets, standing out with unsurpassable clarity upon a transparent yellow background. All was sharp as a sketch with Chinese ink”. The high quality of both the visualization of individual nerve cells and the work performed on studying the anatomy of the central nervous system lead Ramon y Cajal to the conclusion that axons output the nervous impulses to the dendrites or the soma of other target neurons. (shrink)

Biological order provided by α-helical secondary protein structures is an important resource exploitable by living organisms for increasing the efficiency of energy transport. In particular, self-trapping of amide I energy quanta by the induced phonon deformation of the hydrogen-bonded lattice of peptide groups is capable of generating either pinned or moving solitary waves following the Davydov quasiparticle/soliton model. The effect of applied in-phase Gaussian pulses of amide I energy, however, was found to be strongly dependent on the site of (...) application. Moving solitons were only launched when the amide I energy was applied at one of the α-helix ends, whereas pinned solitons were produced in the α-helix interior. In this paper, we describe a general mechanism that launches moving solitons in the interior of the α-helix through phase-modulated Gaussian pulses of amide I energy. We also compare the predicted soliton velocity based on effective soliton mass and the observed soliton velocity in computer simulations for different parameter values of the isotropy of the exciton-phonon interaction. The presented results demonstrate the capacity for explicit control of soliton velocity in protein α-helices, and further support the plausibility of gradual optimization of quantum dynamics for achieving specialized protein functions through natural selection. (shrink)

The essential biological processes that sustain life are catalyzed by protein nano-engines, which maintain living systems in far-from-equilibrium ordered states. To investigate energetic processes in proteins, we have analyzed the system of generalized Davydov equations that govern the quantum dynamics of multiple amide I exciton quanta propagating along the hydrogen-bonded peptide groups in α-helices. Computational simulations have confirmed the generation of moving Davydov solitons by applied pulses of amide I energy for protein α-helices of varying length. The stability (...) and mobility of these solitons depended on the uniformity of dipole-dipole coupling between amide I oscillators, and the isotropy of the exciton-phonon interaction. Davydov solitons were also able to quantum tunnel through massive barriers, or to quantum interfere at collision sites. The results presented here support a nontrivial role of quantum effects in biological systems that lies beyond the mechanistic support of covalent bonds as binding agents of macromolecular structures. Quantum tunneling and interference of Davydov solitons provide catalytically active macromolecular protein complexes with a physical mechanism allowing highly efficient transport, delivery, and utilization of free energy, besides the evolutionary mandate of biological order that supports the existence of such genuine quantum phenomena, and may indeed demarcate the quantum boundaries of life. (shrink)

The Protein Ontology provides terms for and supports annotation of species-specific protein complexes in an ontology framework that relates them both to their components and to species-independent families of complexes. Comprehensive curation of experimentally known forms and annotations thereof is expected to expose discrepancies, differences, and gaps in our knowledge. We have annotated the early events of innate immune signaling mediated by Toll-Like Receptor 3 and 4 complexes in human, mouse, and chicken. The resulting ontology and annotation data (...) set has allowed us to identify species-specific gaps in experimental data and possible functional differences between species, and to employ inferred structural and functional relationships to suggest plausible resolutions of these discrepancies and gaps. (shrink)

Background: Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease, associated with a reciprocal translocation between chromosomes 9 and chromosome 22, lead to the formation of the BCRABL fusion gene (Philadelphia chromosome). This fusion gene is believed to play golden role in the initial development of CML with constitutive tyrosine kinase activation. Successful use of tyrosine kinase inhibiters (TKIs) play a role in improve survival and increase prevalence of CML, but un fortunately mutations in the BCR-ABL kinase domain may (...) cause, or contribute to increase, resistance to TKIs in CML patients. . Objective: This study was designed to assess the association of five most common BCR-ABL kinase domain mutations (T315I, M351T, E255K, M244V and E255V) with resistance state of CML patients on TKIs in Iraqi Middle Euphrates region. Patients and methods: A retrospective case-control study in which 85 patients with chronic myeloid leukemia in chronic phase (45 patients as cases group and 40 patient as control group) were selected from three hemato-oncology centers in middle Euphrates in Iraq during the period from January 2016 till October 2016 out of a total of 240 CML patients (108 male and 132 female) who were registered during this period in these three centers and all patients on TKI (Imatinib and Nilotinib). Venous blood sampling done for BCRABL kinase domain mutations screening. Results: four patients from cases group (4/45) were carriers of one of five selected ABL kinase domain mutations and no one of control group. T315I mutation was detected in 3/45 (6.6 %) of resistant patients, with a significant risk association to develop resistance to TKI therapy (odd ratio and C. I.) (6.67, 0.3340 - 133.2255). E255V was detected in 1/45 (2.2 %) and also had significant risk association to develop resistance to TKIs (odd ratio, C.I.) (2.73, 0.1081 -68.9424). No one of these mutations had significance correlation with demographic or hematological features. M351T, E255K and M244V were not detected in any one of our study groups CML patients. Conclusions: T315I and E255V among five ABL kinas domain mutations were detected in our CML patients with resistance to TKIs. All of them may play a role in development variable degree of resistance to first and second generation TKIs weather primary or secondary.T315I mutation is most common mutation within BCR-ABL domain kinase gene. (shrink)

This article examines Nietzsche’s enduring influence on Deleuze by showing how the interpretation advanced in Nietzsche and Philosophy informs Deleuze’s later work with Guattari. I analyse Deleuze’s reading of the will to power as a typology of forces and his interpretation of the Overman as a pinnacle of creative activity with an eye towards demonstrating that these are not merely Deleuzian creations but are also defensible interpretations of Nietzsche; and I suggest how these portions of Deleuze’s reading of Nietzsche influence (...) his concepts of desiring-production and nomadism, respectively. By analysing Deleuze’s relation to Nietzsche as a longue durée, we can better appreciate how Deleuze’s early reading of Nietzsche is carried forward in his later work. (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)

The article examines the collaborations between the pensionnaires of the Villa Medici in Rome and the members of the French School of Athens, shedding light on the complex relationships between architecture, art, and archeology. The second half of the 19th century was a period during which the exchanges and collaborations between archaeologists, artists, and architects acquired a reinvented role and a dominant place. Within such a context, Athens was the place par excellence, where the encounter between these three disciplines took (...) place. The main objective of the article is to render explicit how the revelations of archeology, actively disseminated by the members of the French School of Athens—the “Athéniens”—had an important impact on the approach of certain pensionnaires of the Villa Medici in Rome. Particular emphasis is placed on certain pensionnaires, who decided to devote their envois to ancient monuments of Greece. In parallel, the article intends to shed light on the methods that helped the pensionnaires-architects of the Villa Medici in Rome appropriate archaeological discoveries concerning Greek antiquities. The article takes, as a starting point, the following hypothesis: to better understand the figure of the architect-archaeologist, of whom Jacques Ignace Hittorff is an emblematic example, it is pivotal to bear in mind that before the second half of the 19th century neither the figure of Hellenic archeology nor the figure of the architect had yet acquired their autonomy. Taking into account that Johann Joachim Winckelmann, in the middle of the 18th century, forged an ideal Greek model, which was criticized during the second half of the 19th century, the article also sheds light on the fact that the revelations of archaeologists have called into question the Winckelmannian image of Greece. Another aspect that is explored in the article is Jacques Ignace Hittorff’s studies concerning the polychromy of ancient Greek monuments, paying special attention to his Restitution du temple d’Empédocle à Sélinonte ou l’Architecture polychrome chez les Grecs. The article also explores how the shifts of the status of philhellenism are related to the mutations of the meaning of travel to Greece. In parallel, it investigates the impact of Greek independence on the ideals of beauty and nature in arts, as well as how Greek independence is related to the intensification of the interest in the excavations of Greek antiquities. (shrink)

Abstract: Sickle cell disease (SCD) comprises an inherited blood disorder that is life long and affects many people globally. Despite progress in therapy, SCA is a considerable cause of mortality and morbidity. This study was designed to measure the immunological and inflammatory parameters of patients with sickle cell disease (SCD) and to found if there is any role of it in the pathogenicity of the disease. This study included A total of 32 patients, their ages ranged from 16 to 55 (...) years patients with Sickle cell disease who have been evaluated during vaso occlusive crisis and had been followed up till they attained steady state, and there are 32 normal control subjects matched with patients in age and sex. In general there was elevation in all parameters the study were included in patients than control and particularly in crisis, despite the IgM value which was insignificantly decrease, but the statically significant elevation reported only in CRP, IgG, IgA. (shrink)

A planetary panic and almost deserted cities, fear of food shortages, and the growing threat of an invisible virus that does more damage day by day. In the time of the COVID-19 pandemic, many believe that science fiction has now been overtaken by reality. In these times of adversity, what does it take to survive when the world comes crashing down? How do humans stay resilient, manage their growing stress, and somehow navigate through the crisis? More specifically, how do humans (...) cope with isolation and loneliness in the light of a global outbreak? What does science fiction have to tell us about this? For the bewildered population, science fiction has been recognized as an ingredient to understand an unexpected reality. In this article I explain, through the philosophical eye of Francis Lawrence’s movie I Am Legend (2007), how a coping skill such as imagination, in the age of pandemics and social distancing, can mutate into a “Second Reality” that fills the gap left by the former (pre-outbreak) reality. (shrink)

Macromolecular protein complexes catalyze essential physiological processes that sustain life. Various interactions between protein subunits could increase the effective mass of certain peptide groups, thereby compartmentalizing protein α-helices. Here, we study the differential effects of applied massive barriers upon the soliton-assisted energy transport within proteins. We demonstrate that excentric barriers, localized onto a single spine in the protein α-helix, reflect or trap three-spine solitons as effectively as concentric barriers with comparable total mass. Furthermore, wider protein (...) solitons, whose energy is lower, require heavier massive barriers for soliton reflection or trapping. Regulation of energy transport, delivery and utilization at protein active sites could thus be achieved through control of the soliton width, or of the effective mass of the protein subunits. (shrink)

Neutrosophic Genetics is the study of genetics using neutrosophic logic, set, probability, statistics, measure and other neutrosophic tools and procedures. In this paper, based on the Neutrosophic Theory of Evolution (that includes degrees of Evolution, Neutrality (or Indeterminacy), and Involution) – as extension of Darwin’s Theory of Evolution, we show the applicability of neutrosophy in genetics, and we present within the frame of neutrosophic genetics the following concepts: neutrosophic mutation, neutrosophic speciation, and neutrosophic coevolution.

that can serve as a foundation for more refined ontologies in the field of proteomics. Standard data sources classify proteins in terms of just one or two specific aspects. Thus SCOP (Structural Classification of Proteins) is described as classifying proteins on the basis of structural features; SWISSPROT annotates proteins on the basis of their structure and of parameters like post-translational modifications. Such data sources are connected to each other by pairwise term-to-term mappings. However, there are obstacles which stand in the (...) way of combining them together to form a robust meta-classification of the needed sort. We discuss some formal ontological principles which should be taken into account within the existing datasources in order to make such a metaclassification possible, taking into account also the Gene Ontology (GO) and its application to the annotation of proteins. (shrink)

Cancer research is experiencing ‘paradigm instability’, since there are two rival theories of carcinogenesis which confront themselves, namely the somatic mutation theory and the tissue organization field theory. Despite this theoretical uncertainty, a huge quantity of data is available thanks to the improvement of genome sequencing techniques. Some authors think that the development of new statistical tools will be able to overcome the lack of a shared theoretical perspective on cancer by amalgamating as many data as possible. We think (...) instead that a deeper understanding of cancer can be achieved by means of more theoretical work, rather than by merely accumulating more data. To support our thesis, we introduce the analytic view of theory development, which rests on the concept of plausibility, and make clear in what sense plausibility and probability are distinct concepts. Then, the concept of plausibility is used to point out the ineliminable role played by the epistemic subject in the development of statistical tools and in the process of theory assessment. We then move to address a central issue in cancer research, namely the relevance of computational tools developed by bioinformaticists to detect driver mutations in the debate between the two main rival theories of carcinogenesis. Finally, we briefly extend our considerations on the role that plausibility plays in evidence amalgamation from cancer research to the more general issue of the divergences between frequentists and Bayesians in the philosophy of medicine and statistics. We argue that taking into account plausibility-based considerations can lead to clarify some epistemological shortcomings that afflict both these perspectives. (shrink)

Chemical kinds (e.g. gold) are generally treated as having timelessly fixed identities. Biological kinds (e.g. goldfinches) are generally treated as evolved and/or evolving entities. So what kind of kind is a biochemical kind? This paper defends the thesis that biochemical molecules are clustered chemical kinds, some of which–namely, evolutionarily conserved units–are also biological kinds.On this thesis, a number of difficulties that have recently occupied philosophers concerned with proteins and kinds are shown to be resolved or dissolved.

Historically, hypotheses failed in most cases to correctly forecast the workings of complex biological systems. Francis Crick’s adaptor hypothesis, however, stands out as an exceptional case of a confirmed abstract prediction. This hypothesis presciently anticipated the existence of RNA adaptors that function as bridges between amino acids and the chemically different nucleic acid template for proteins. Crick conjectured that the adaptors are enzymatically charged with cognate amino acids, they bind to complementary protein-coding nucleic acid, and their liberated amino acids (...) are incorporated into growing protein chains. Independently from and concomitantly with Crick’s hypothesis, Mahlon Hoagland and Paul Zamecnik conducted experiments with no guiding theory that culminated in discoveries of the actual adaptors, transfer RNA (tRNA) molecules, and their amino acids charging enzymes. This paper traces the parallel histories of Crick’s adaptor hypothesis and of the experimental discovery of tRNA and compares their relative impacts on the scientific community. Remarkably, despite the brilliance of Crick’s confirmed prognostication, it had marginal impact on practicing scientists. Conversely, Hoagland and Zamecnik’s experimental discoveries and their evidence-based model of protein synthesis had immediate and enduring impact. I discuss possible explanations for the different impacts of the theoretical prediction and experimental identifications of the same entities. (shrink)

The extent to which normal (nonmalignant) cells of the body can evolve through mutation and selection during the lifetime of the organism has been a major unresolved issue in evolutionary and developmental studies. On the one hand, stable multicellular individuality seems to depend on genetic homogeneity and suppression of evolutionary conflicts at the cellular level. On the other hand, the example of clonal selection of lymphocytes indicates that certain forms of somatic mutation and selection are concordant with the (...) organism-level fitness. Recent DNA sequencing and tissue physiology studies suggest that in addition to adaptive immune cells also neurons, epithelial cells, epidermal cells, hematopoietic stem cells and functional cells in solid bodily organs are subject to evolutionary forces during the lifetime of an organism. Here we refer to these recent studies and suggest that the expanding list of somatically evolving cells modifies idealized views of biological individuals as radically different from collectives. (shrink)

The problem with reductionism in biology is not the reduction, but the implicit attitude of determinism that usually accompanies it. Methodological reductionism is supported by deterministic beliefs, but making such a connection is problematic when it is based on an idea of determinism as fixed predictability. Conflating determinism with predictability gives rise to inaccurate models that overlook the dynamic complexity of our world, as well as ignore our epistemic limitations when we try to model it. Furthermore, the assumption of a (...) strictly deterministic framework is unnecessarily hindering to biology. By removing the dogma of determinism, biological methods, including reductive methods, can be expanded to include stochastic models and probabilistic interpretations. Thus, the dogma of reductionism can be saved once its ties with determinism are severed. In this paper, I analyze two problems that have faced molecular biology for the last 50 years—protein folding and cancer. Both cases demonstrate the long influence of reductionism and determinism on molecular biology, as well as how abandoning determinism has opened the door to more probabilistic and unconstrained reductive methods in biology. (shrink)

The cashew nut is essential for physical and emotional well-being. It is an energetic diet and the best food medication for many illnesses. Nuts protects from malignant growth, coronary illness, circulatory strain, and various degenerative infirmities connected to aging. It can be used for several medicinal purposes. Every part of cashew has some important medicinal properties. Cashew kernel contains proteins, carbohydrates, vitamins, and fats which help gain energy. Cashew nuts are used for many purposes like blood sugar, weight loss, cancer, (...) cold and flu, aging, urinary disorders, digestive disorders, and bone relaxation. In comparing cashew with other nuts, Cashew kernels have good properties, including proteins, carbohydrates, fibers, and minerals, then almond, hazelnut, and walnuts. Cashew kernels contain the highest number of proteins (21%) when compared with Almonds (20.8%), Hazelnuts (15.6%), and Macadamia Nuts (60.9%). Cashew contain large amount of carbohydrate (22%) compared to other nuts like almonds, walnuts, etc. There are some strong benefits of Cashew for health. They boost the immune system, act as an antioxidant, remove gallstones, and beneficial for anemia. They are good sources of healthy fats that are necessary for our body to absorb fat-soluble vitamins. Its bark is known as the antihypertensive and glucose-lowering part. It has beneficial effect on the eyes and skin. This is rich in vitamin C, so it can be used for skin problems like acne, flawless freckles, skin lines and protects from aging. (shrink)

Upon separation of the protein from the nucleic acid component of tobacco mosaic virus by phenol, using a fast and gentle procedure, the nucleic acid is infective in assays on tobacco leaves. A series of qualitative and quantitative control experiments demonstrates that the biological activity cannot depend on residual proteins in the preparation, but is a property of isolated nucleic acid which is thus the genetic material of the virus.

Abstract The quasispecies theory is a helpful concept in the explanation of RNA virus evolution and behaviour, with a relevant impact on methods used to fight viral diseases. It has undergone some adaptations to integrate new empirical data, especially the non-deterministic nature of mutagenesis, and the variety of behavioural motifs in cooperation, competition, communication, innovation, integration, and exaptation. Also, the consortial structure of quasispecies with complementary roles of memory genomes of minority populations better fits the empirical data than did the (...) original concept of a master sequence and its mutant spectra. The high productivity of quasispecies variants generates unique sequences that never existed before and will never exist again. In the present essay, we underline that such sequences represent really new ontological entities, not just error copies of previous ones. Their primary unique property, the incredible variant production, is suggested here as quasispecies productivity, which replaces the error-replication narrative to better fit into a new relationship between mankind and living nature in the twenty-first century. (shrink)

Biomolecules and particularly proteins and DNA exhibit some mysterious features that cannot find satisfactory explanation by quantum mechanical modes of atoms. One of them, known as a Levinthal’s paradox, is the ability to preserve their complex three-dimensional structure in appropriate environments. Another one is that they possess some unknown energy mechanism. The Basic Structures of Matter Supergravitation Unified Theory (BSM-SG) allows uncovering the real physical structures of the elementary particles and their spatial arrangement in atomic nuclei. The resulting physical models (...) of the atoms are characterized by the same interaction energies as the quantum mechanical models, while the structure of the elementary particles influence their spatial arrangement in the nuclei. The resulting atomic models with fully identifiable parameters and angular positions of the quantum orbits permit studying the physical conditions behind the structural and bonding restrictions of the atoms connected in molecules. A new method for a theoretical analysis of biomolecules is proposed. The analysis of a DNA molecule leads to formulation of hypotheses about the energy storage mechanism in DNA and its role in the cell cycle synchronization. This permits shedding a light on the DNA feature known as a C-value paradox. The analysis of a tRNA molecule leads to formulation of a hypothesis about a binary decoding mechanism behind the 20 flavors of the complex aminoacyle-tRNA synthetases - tRNA, known as a paradox. (shrink)

While Darwin is commonly supposed to have demonstrated the inapplicability of the Aristotelian ontology of species to biological science, recent developments, especially in the wake of the Human Genome Project, have given rise to a new golden age of classification in which ontological ideas -- as for example in the Gene Ontology, the Cell Ontology, the Protein Ontology, and so forth -- are once again playing an important role. In regard to species, on the other hand, matters are more (...) complex. We provide a brief overview of recent proposals concerning the ontology of species, dealing with species as sets, classes and as collections, the views of Ernst Meyr, and mereological views. (shrink)

It has become customary to conceptualize the living cell as an intricate piece of machinery, different to a man-made machine only in terms of its superior complexity. This familiar understanding grounds the conviction that a cell's organization can be explained reductionistically, as well as the idea that its molecular pathways can be construed as deterministic circuits. The machine conception of the cell owes a great deal of its success to the methods traditionally used in molecular biology. However, the recent introduction (...) of novel experimental techniques capable of tracking individual molecules within cells in real time is leading to the rapid accumulation of data that are inconsistent with an engineering view of the cell. This paper examines four major domains of current research in which the challenges to the machine conception of the cell are particularly pronounced: cellular architecture, protein complexes, intracellular transport, and cellular behaviour. It argues that a new theoretical understanding of the cell is emerging from the study of these phenomena which emphasizes the dynamic, self-organizing nature of its constitution, the fluidity and plasticity of its components, and the stochasticity and non-linearity of its underlying processes. (shrink)

This article evaluates Furio Jesi’s conception of mythic violence, focusing in particular on his theory of revolt as a mode of collective experience qualitatively distinct from that of revolution. Jesi offers both a descriptive phenomenology of how uprisings alter the human experience of time and action, as well as a critique of the “autonomy” these moments afford their participants. In spite of their immense transformative power to interrupt historical time and generate alternate forms of collective subjectivation, the event-like structure of (...) revolt also harbors within it a unique set of dangers. Such creative mutations risk trapping political actors within a relational logic of the exception, a “ban” structure that, although distinct from the atomization that governs normal time, ultimately works to reinforce it in the long run. The article concludes by suggesting that Jesi’s late concept of the “cruel festival” offers a troubling premonition of our current era, in which revolts proliferate in the absence of any ideological horizon of revolution. (shrink)

The fight to find effective, long-lasting treatments for cancer has led many researchers to consider protein degrading entities. Recent developments in PROteolysis TArgeting Chimeras (PROTACs) have signified their potential as possible cancer therapies. PROTACs are small molecule, protein degraders that function by hijacking the built-in Ubiquitin-Proteasome pathway. This review mainly focuses on the general design and functioning of PROTACs as well as current advancements in the development of PROTACs as anticancer therapies. Particular emphasis is given to PROTACs designed (...) against various types of Leukemia/Blood malignancies. (shrink)