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)

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)

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.

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)

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)

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)

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. -/- .

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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.

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)

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.

Different chemical species are often cited as paradigm examples of structurally delimited natural kinds. While classificatory monism may thus seem plausible for simple molecules, it looks less attractive for complex biological macromolecules. I focus on the case of proteins that are most plausibly individuated by their functions. Is there a single, objective count of proteins? I argue that the vagaries of function individuation infect protein classification. We should be pluralists about macromolecular classification.

The purpose of this study was to compare the nutrient contents and phytochemical composition of the leaves, roots, and stem bark of Cissus populnea. The specimens came from Nsukka in Nigeria's Enugu State. Laboratory experimental design was used for this study. Samples of leaves, roots, and stem barks were prepared by drying them for two hours at 50 0C in a food dehydrator, ground into fine powder and dried again using the air-drying process The analyses were carried out using standard (...) methods. The proximate analyses showed that the samples contain crude protein (1.89 - 2.11%), crude fibre (22.23 - 22.48%), crude fat (1.99 - 2.09%), carbohydrates (43.71 - 64.96%), ash (4.11 - 6.64%) and moisture (4.46- 4.84%). The phytochemical data showed that all plant components contained phenol, alkaloids, tannins, and terpenoids, but not steroids. Both saponin and flavoloid were found in the plant's roots and leaves only. Flavonoid was not detected in the stem. The results of mineral compositions showed that the root, stem, and leaf samples included potassium (340.83 – 439.33 mg/100g) calcium (132.99 – 295.78 mg/100g), iron (1.12 – 4.21 mg/100g), magnesium (27.41- 39.67 mg/100g) and manganese (0.14 – 3.99 mg/100g). Because of its nutrient contents and phytochemical proportions, consumers are encouraged to use any parts, though root parts of the plant seem to contain high nutrient. (shrink)

Space Time Information (a thought experiment) proves that protein evolution is the result of computation: possibly due to a simulation.

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)

Previous studies have shown that zinc deficiency leads to apoptosis of neuronal precursor cells in vivo and in vitro. In addition to the role of p53 as a nuclear transcription factor in zinc deficient cultured human neuronal precursors (NT-2), we have now identified the translocation of phosphorylated p53 to the mitochondria and p53-dependent increases in the pro-apoptotic mitochondrial protein BAX leading to a loss of mitochondrial membrane potential as demonstrated by a 25% decrease in JC-1 red:green fluorescence ratio. Disruption (...) of mitochondrial membrane integrity was accompanied by efflux of the apoptosis inducing factor (AIF) from the mitochondria and translocation to the nucleus with a significant increase in reactive oxygen species (ROS) after 24 h of zinc deficiency. Measurement of caspase cleavage, mRNA, and treatment with caspase inhibitors revealed the involvement of caspases 2, 3, 6, and 7 in zinc deficiency-mediated apoptosis. Down-stream targets of caspase activation, including the nuclear structure protein lamin and polyADP ribose polymerase (PARP), which participates in DNA repair, were also cleaved. Transfection with a dominant-negative p53 construct and use of the p53 inhibitor, pifithrin- ␮, established that these alterations were largely dependent on p53. Together these data identify a cascade of events involving mitochondrial p53 as well as p53-dependent caspase-mediated mechanisms leading to apoptosis during zinc deficiency. (shrink)

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)

Objective: Lung cancer is the most common cause of morbidity and mortality. Platinum-based chemotherapy, which is the primary line of treatment, offers limited benefit due to drug resistance and side effects. Berberine (BBR), which is characterised by its potent and safe anticancer activity, represents a promising combination option in chemotherapy. To overcome the limitations in lung cancer chemotherapy, we investigated whether BBR and cisplatin (CIS) exert synergistic effects on non-small cell lung cancer cell line (A549) based on cytotoxicity and apoptotic (...) response markers. -/- Methods: The potential cytotoxic effects of the combination treatment were evaluated using the MTT and Chou-Talalay methods. Elisa assays were also performed to measure the levels of the pro-apoptotic protein Bax and the effector protein caspase (Cas)-3. -/- Results: The results showed that BBR alone reduced A549 cell viability in a dose-dependent manner and synergized with CIS (CI =0.34±0.05 at IC50 concentrations). Elisa results showed that the combined treatment (both at IC50 concentrations) modulated apoptotic signalling pathways in A549 cells. Bax and Cas3 protein levels were dramatically enhanced in A549 cells treated with CIS +BBR compared to control (0.5% DMSO) (p < 0.001). -/- Conclusion: Our results suggest that BBR can synergistically enhance the therapeutic effect of CIS in A549 cells. The potential therapeutic efficacy of BBR as part of a combination in current chemotherapy should be supported by in-depth research and clinical studies on the molecular mechanisms associated with cancer. (shrink)

This essay examines the relationship between metabolic brain processes and psycho-physiological activities or mental activity. It is argued that metabolic brain processes, including those involved in the production of energy, proteins and other molecules are restorative and conditional, rather than directly involved in mental activities. This stance suggests that life-time acquired learning and memory is precipitated as a permanent and personal configuration of the brain, that is in principle accessible to neurophysiological examination. Current neuroscience largely ignores implicitly or explicitly the (...) search for new emergent configurations of the brain. (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)

The unit of selection is the concept of that ‘something’ to which biologists refer when they speak of an adaptation as being ‘for the good of’ something. Darwin identified the organism as the unit of selection because for him the ‘struggle for existence’ was an issue among individuals. Later on it was suggested that, in order to understand the evolution of social behavior, it is necessary to argue that groups, and not individuals, are the units of selection. The last addition (...) to this debate was the formulation by Dawkins, in 1976, that the genes themselves are the units of selection while organisms are merely the temporary receptacles and vehicles for such genes. Thus, the preposterous dissolution of the organism into genes and the proteins coded by such genes has been introduced in the evolutionary discourse by neglecting that the explanations for biological phenomena can be either synchronic or diachronic, depending on the phenomenon to be explained. Therefore explanations in molecular biology are synchronic while evolutionary biology needs diachronic explanations. Nevertheless, for ultra-Darwinians such as Dawkins, efficient replication is all that biology is about. Here I develop an argument in order to show that there is nothing in molecular and cell biology that might support such a contention and that the idea of the gene as the unit of selection is incompatible with the evident evolution of biological complexity. (shrink)

Following Kripke and Putnam, the received view of chemical kinds has been a microstructuralist one. To be a microstructuralist about chemical kinds is to think that membership in said kinds is conferred by microstructural properties. Recently, the received microstructuralist view has been elaborated and defended, but it has also been attacked on the basis of complexities, both chemical and ontological. Here, I look at which complexities really challenge the microstructuralist view; at how the view itself might be made more complicated (...) in order to accommodate such challenges; and finally, at what this increasingly complicated picture implies for our standard assessment of chemical kindhood—primarily, for the widespread assumption that chemical kinds in general are more neat and tidy than those messy biological ones. _1_ The Received View _2_ A Taxonomy of Chemical Kinds _3_ Atomic Number _4_ H2O, H3O+, OH−, and More _5_ Complicating the Microstructuralist Picture _6_ Concrete and Other Mixtures _7_ Macromolecules, Especially Proteins _8_ Abandoning Sameness of Elemental Composition _9_ Not So Different after All. (shrink)

In a now classic paper published in 1991, Alberch introduced the concept of genotype–phenotype (G!P) mapping to provide a framework for a more sophisticated discussion of the integration between genetics and developmental biology that was then available. The advent of evo-devo first and of the genomic era later would seem to have superseded talk of transitions in phenotypic space and the like, central to Alberch’s approach. On the contrary, this paper shows that recent empirical and theoretical advances have only sharpened (...) the need for a different conceptual treat- ment of how phenotypes are produced. Old-fashioned metaphors like genetic blueprint and genetic programme are not only woefully inadequate but positively misleading about the nature of G!P, and are being replaced by an algorithmic approach emerging from the study of a variety of actual G!P maps. These include RNA folding, protein function and the study of evolvable soft- ware. Some generalities are emerging from these disparate fields of analysis, and I suggest that the concept of ‘developmental encoding’ (as opposed to the classical one of genetic encoding) provides a promising computational–theoretical underpinning to coherently integrate ideas on evolvability, modularity and robustness and foster a fruitful framing of the G!P mapping problem. (shrink)

This paper explores the evolution of consciousness and subjectivity through a biological framework for understanding the universe. It posits that functional patterns in biological systems mirror cosmic mathematical principles, defining our objective reality. Similar to wave and Fibonacci patterns in different physical phenomena, biological patterns are intrinsic to all things and can be quantified using Dedre Gentner’s approach to analogy. For example, Earth’s ocean currents and the melting and freezing of Antarctica resemble the circulatory system and heart, while the production (...) of music from instruments is analogous to ribosomal protein synthesis. Shelves, tables, and chairs function like cytosol by holding objects in space, and a coffee cup mirrors red blood cell distribution. These analogies reveal a universal order rooted in biology’s functional patterns, essential for shaping the emergence and evolution of life. The paper traces the development of consciousness from its rudimentary cellular states to complex human cognition, highlighting the role of biologically-patterned environments in driving evolutionary changes. Organisms that recognized and organized according to these patterns evolved as “pattern recognition engines” crucial for survival—thus, Life (survival) being the primary measure of consciousness. Humans advanced this capacity, gaining cognitive freedom by insulating themselves from environmental constraints, but faced increased subjectivity complexity. Consciousness, while inherently subjective and necessary for cognitive development, evolves in humans to understand objective reality and its biological nature, so to understand and navigate complexities of subjectivity. Ultimately, the paper asserts consciousness is the ability to recognize and adhere to life-sustaining patterns and principles. Successful adherence deems them worthy of continued existence, while failure leads to demise. Parallels with historical concepts like Atman and Brahman in Hinduism suggest ancient recognition of the correspondence between human and universal patterns. This ancient understanding, coupled with modern scientific evidence, reveals the interconnectedness and intrinsic biological nature of reality. (shrink)

The biomedical literature makes extensive use of the concept of a genetic program. So far, however, the nature of genetic programs has received no satisfactory elucidation from the standpoint of computer science. This unsettling omission has led to doubts about the very existence of genetic programs, on the grounds that gene regulatory networks lack a predetermined schedule of execution, which may seem to contradict the very idea of a program. I show, however, that we can make perfect sense of genetic (...) programs, if only we abandon the preconception that all computers have a von Neumann architecture. Instead, genetic programs instantiate the computational architecture of Post–Newell Production Systems. That is, genetic programs are unordered sets of conditional instructions, instructions that fire independently when their conditions are matched. For illustration I present a paradigm Production System that regulates the functioning of the well-known lac operon of E. coli. On close reflection it turns out that not only genes, but also proteins encode instructions. I propose, therefore, to rename genetic programs to biomolecular programs. Biomolecular and/or genetic programs, and the cellular computers than run them, are to be understood not as von Neumann computers, but as Post–Newell production systems. (shrink)

We propose a novel paradigmatic approach to sentient reality as a whole, with specific application to Information-guided DNA dynamics, leading to a triadic genomic configuration , which accommodates besides the parental hereditar legacy, a transcendental originating highly complex guiding matrix able to control the specific way the protein-synthesis is performed. The Self’s own “Soul Genome”, transcending the zero point energy interdimensional barrier, couples to the zygote’s quantum-governed energetic configuration by way of resonant bands of subtle energy superposition effects at (...) the instance of fertilization, triggered by a Zinc-spark related biophotonic bridge. Thus, unique secondary torsion parameters in the DNA strands determine the way the basic protein-generating template is read, supplying the new entity’s psycho-cognitive particularities along purposeful developmental vectors. (shrink)

The mathematical universe hypothesis is a theory that the physical universe is not merely described by mathematics, but is mathematics, specifically a mathematical structure. Our research provides evidence that the mathematical structure of the universe is biological in nature and all systems, processes, and objects within the universe function in harmony with biological patterns. Living organisms are the result of the universe’s biological pattern and are embedded within their physiology the patterns of this biological universe. Therefore physiological patterns in living (...) organisms can be used as models to structurally map analogies from the biological domain to any target domain to reveal and understand the biological nature of the target domain. Our paper explores various analogies, structurally mapping a red blood cell to a cup; proteins produced from ribosomes to music produced from instruments; a beating heart to the melting and freezing of Antartica; cells, tissue, organs and blood, to people, organizations, industries, and money, and; bio-economic concepts in cellular society to socioeconomic concepts in human society. It also discusses how phenomena in cellular mitosis can help explain phenomena in the universe, such as black holes, dark matter, dark energy, and the structure of the universe. Building upon the concept of perennial wisdom, our research has provided evidence that the ideas of a biological universe were expressed across many past cultures and historical periods. The implications of this theory are vast, encompassing fields such as physics, science, philosophy, religion, law, economics, politics, and engineering, thus serving as a unifying theory for all knowledge. Our theory is supported by meta-analysis of scientific, historic, and religious literature, observations and first principles logic. (shrink)

The development of cultured meat has gained urgency through the increasing problems associated with meat, but what it might become is still open in many respects. In existing debates, two main moral profiles can be distinguished. Vegetarians and vegans who embrace cultured meat emphasize how it could contribute to the diminishment of animal suffering and exploitation, while in a more mainstream profile cultured meat helps to keep meat eating sustainable and affordable. In this paper we argue that these profiles do (...) not exhaust the options and that feelings as well as imagination are needed to explore possible future options. On the basis of workshops, we present a third moral profile, “the pig in the backyard”. Here cultured meat is imagined as an element of a hybrid community of humans and animals that would allow for both the consumption of animal protein and meaningful relations with domestic animals. Experience in the workshops and elsewhere also illustrates that thinking about cultured meat inspires new thoughts on “normal” meat. In short, the idea of cultured meat opens up new search space in various ways. We suggest that ethics can take an active part in these searches, by fostering a process that integrates feelings, imagination and rational thought and that expands the range of our moral identities. (shrink)

Background: A bean is the seed of one of several genera of the flowering plant family Fabaceae, which are used as vegetables for human or animal food. They can be cooked in many different ways, including boiling, frying, and baking, and are used in many traditional dishes throughout the world. Beans are one of the longest-cultivated plants. Broad beans, also called fava beans, in their wild state the size of a small fingernail, were gathered in Afghanistan and the Himalayan foothills. (...) In a form improved from naturally occurring types, Beans were an important source of protein throughout old and new world history, and still are today. Objectives: The main goal of this expert system is to get the appropriate diagnosis of disease and the correct treatment. Methods: In this paper, the design of the proposed Expert System was produced to help farmers and those interested in agriculture in diagnosing many of the Bean diseases such as Fusarium wilt, Charcoal rot or ashy stem blight, Bacterial leaf spot and blight, Mung bean yellow mosaic virus, Cercospora leaf spot. The proposed expert system presents an overview of Bean diseases are given, the cause of diseases outlined and the treatment of disease whenever possible is given out. CLIPS Expert System language was used for designing and implementing the proposed expert system. Results: The proposed Bean diseases diagnosis expert system was evaluated by Agricultural experts and some friends interested in agriculture and they were satisfied with its performance. Conclusions: The proposed expert system is very useful for Farmers and those interested in agriculture. (shrink)

We introduce a new type of pluralism about biological function that, in contrast to existing, demonstrates a practical integration among the term’s different meanings. In particular, we show how to generalize Sandra Mitchell’s notion of integrative pluralism to circumstances where multiple epistemic tools of the same type are jointly necessary to solve scientific problems. We argue that the multiple definitions of biological function operate jointly in this way based on how biologists explain the evolution of protein function. To clarify (...) how our account relates to existing views, we introduce a general typology for monist and pluralist accounts along with standardized criteria for judging which is best supported by evidence. (shrink)

Because factory-farmed meat production inflicts gratuitous suffering upon animals and wreaks havoc on the environment, there are morally compelling reasons to become vegetarian. Yet industrial plant agriculture causes the death of many field animals, and this leads some to question whether consumers ought to get some of their protein from certain kinds of non factory-farmed meat. Donald Bruckner, for instance, boldly argues that the harm principle implies an obligation to collect and consume roadkill and that strict vegetarianism is thus (...) immoral. But this argument works only if the following claims are true: all humans have access to roadkill, roadkill would go to waste if those who happen upon it don’t themselves consume it, it’s impossible to harvest vegetables without killing animals, the animals who are killed in plant production are all-things-considered harmed by crop farming, and the best arguments for vegetarianism all endorse the harm principle. As I will argue in this paper, each claim is deeply problematic. Consequently, in most cases, humans ought to strictly eat plants and save the roadkill for cats. (shrink)

In the wake of the advent of genome editing technology CRISPR-Cas9 (clustered regularly interspaced palindromic repeat (CRISPR)-associated protein 9), there has been a global debate around the implications of manipulating the human genome. While CRISPR-based germline gene editing is new, the debate about the ethics of gene editing is not – for several decades now, scholars have debated the ethics of making heritable changes to the human genome. The arguments that have been raised both for and against the use (...) of genetic technologies in human reproduction reiterate much of the arguments made in the pre-CRISPR debate. As such, it is instructive for South Africa to reflect on these arguments now, in considering our position on the regulation of the use of this novel biotechnology. There are two dominant schools of thought in this area, bioliberalism and bioconservatism. Bioconservatives raise concerns about the risks of genetic manipulation, and argue that it ought to be limited or prohibited to avert these risks to human health and human nature. Bioliberal scholars are more open to the prospect of genetic manipulation, because of its potential utility. In this article, I conclude that in liberal democracies such as our own, bioliberal arguments ought to be seriously considered when formulating policy on human genome editing because of the extent to which they resonate with our Constitutional values and human rights. I further suggest that there is a need for an enquiry into the relevance of African perspectives on the ethical questions that arise concerning germline genome editing. (shrink)

Synthetic biology (SynBio) covers two main areas: application engineering, exemplified by metabolic engi- neering, and the design of life from artificial building blocks. As the general public is often reluctant to embrace synthetic approaches, preferring nature to artifice, its immediate future will depend very much on the public’s reaction to the unmet needs created by the pervasive demands of sustainability. On the other hand, this reluctance should not have a negative impact on research that will now take into account the (...) existence of the multiple transitions that cells face over time. The ages of life—birth, development, maturation, senescence and death—reflect specific key transitions and have, until now, rarely been taken into account in SynBio designs. This results in a mismatch between novelty and the very long evolutionary time that led to the existing chassis [remember that this is the common term used to describe the cellular framework as seen by synthetic biologists (de Lorenzo & Danchin, 2008)]. It also implies that, in general, transitions between growth stages will be taken into account with the appro- priate embodiment of highly specific processes. This is particularly important when adapting new models to their host, whether natural or artificial. Adaptation fol- lows two stages, short-term accommodation of new entities and long-term assimilation into the cell as a whole. This requires discrimination between classes of entities. We suggest that proteins playing the essential role of Maxwell’ demons, here named Maxwell’s dis- criminators (MxDs) to refer to their original function, will permit the assimilation and accommodation of artificial constructs. As a consequence, we can foresee that class discrimination, beyond mere recognition, will be implemented in SynBio 2.0, leading to an authentic par- adigm shift (Kuhn, 1996), based on conceptions that embody information as a genuine currency of reality. (shrink)

Abstract: Fish are important for both nutritional and economic reasons. They are a good source of protein, vitamins, and minerals and play a significant role in human diets, especially in coastal and island communities. In addition, fishing and fish farming are major industries that provide employment and income for millions of people worldwide. Moreover, fish play a critical role in marine ecosystems, serving as prey for larger predators and helping to maintain the balance of aquatic food chains. Overall, fish (...) play a vital role in supporting human well-being and the health of our planet. . Fishes have a lots of types such that: Red Mullet, Sea Bass, Striped Red Mullet and Shrimp. Each of them has its own shape and characteristics that differ from other types. We proposed a system that recognize nine types of fishes using deep learning. We trained the model with a dataset that contain 9000 images that were slit into 6300 images for training, 1350 for validation and 1350 for testing. The proposed model achieved accuracy (99.68%), precision (99.69%), recall (99.68%), and f1-score (99.68%). This indicates that our proposed model can effectively predicate and classify different types of fish with very high accuracy. (shrink)

Cells are cognitive entities possessing great computational power. DNA serves as a multivalent information storage medium for these computations at various time scales. Information is stored in sequences, epigenetic modifications, and rapidly changing nucleoprotein complexes. Because DNA must operate through complexes formed with other molecules in the cell, genome functions are inherently interactive and involve two-way communication with various cellular compartments. Both coding sequences and repetitive sequences contribute to the hierarchical systemic organization of the genome. By virtue of nucleoprotein complexes, (...) epigenetic modifications, and natural genetic engineering activities, the genome can serve as a read-write storage system. An interactive informatic conceptualization of the genome allows us to understand the functional importance of DNA that does not code for protein or RNA structure, clarifies the essential multidirectional and systemic nature of genomic information transfer, and emphasizes the need to investigate how cellular computation operates in reproduction and evolution. (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)