Nucleic acid hybridization is being increasingly used in viral diagnosis. Most of the assays described so far for this purpose require the use of radioactive probes. Their replacement by Non‐radioactive assays has many advantages and makes the technique feasible in routine diagnostic work. Non‐radioactive assays have had limited use but their diagnostic value has been demonstrated for a number of virus infections. They have the main advantages of employing stable probes, of avoiding safety hazards and of being (...) easy and rapid to perform with limited laboratory facilities. Their main disadvantage compared to radioactive assays is in having relatively low sensitivity. Improvements in probe construction, in labelling and detecting methods, in sample treatment and in hybridization conditions may well increase their usefulness. (shrink)

The use of molecules and reactions as evidence, markers and/or traits for evolutionary processes has a history more than a century long. Molecules have been used in studies of intra-specific variation and studies of similarity among species that do not necessarily result in the analysis of phylogenetic relations. Promoters of the use of molecular data have sustained the need for quantification as the main argument to make use of them. Moreover, quantification has allowed intensive statistical analysis, as a condition and (...) a product of increasing automation. All of these analyses are subject to the methodological anxiety characteristic of a community in search of objectivity. It is in this context that scientists compared and evaluated protein and nucleic acid sequence data with other types of molecular data – including immunological, electrophoretic and hybridization data. This paper argues that by looking at long-term historical processes, such as the use of molecular evidence in evolutionary biology, we gain valuable insights into the history of science. In that sense, it accompanies a growing concern among historians for big-pictures of science that incorporate the fruitful historical research on local cases of the last decades. (shrink)

This article examines how a molecular "solution" to an important biological problem-how is antibody diversity generated? was obtained in the 1970s. After the primarily biological clonal selection theory (CST) was accepted by 1967, immunologists developed several different contrasting theories to complete the SCST. To choose among these theories, immunology had to turn to the new molecular biology, first to nucleic acid hybridization and then to recombinant DNA technology. The research programs of Tonegawa and Leder that led to (...) the "solution" are discussed, and some of their strategies and heuristics are broadly characterized: (1) to what extent does the new recombinant DNA technology provide what the scientists claim is "direct evidence," what does that term mean, and what are the implications of that claim for biological "realism," and (2) is this episode one of reduction, partial reduction, or explanatory extension, and what do these terms mean in the context of a successful molecular "solution" to a biological problem. (shrink)

The paper tries to show that an evolutionary perspective helps us to address what is called the adaptation problem, that is, the remarkable coherence, and seemingly successful design, existing between our cognitive tools and the phenomena of the material world. It argues that a fine-grained description of the structure and function of experimental techniques—as a special type amongst evolving scientific practices—is a condition for a better understanding and, ultimately, an explanation of how adaptation among the heterogeneous elements of experimental knowledge (...) is attained. Some apparently contradictory features of techniques, such as their high context-dependency and their capabilities to reproduce and diversify outside their original contexts, are addressed with the help of the concepts of technical variation and the historical entrenchment of phenomena in techniques. In order to do so, a case-study on the construction of satellite-DNA and the evolution of nucleic acid hybridization, a research project carried out by Roy J. Britten and his colleagues in the 1960s, is presented in detail. This case illustrates the close relationship existing between the evolution of techniques and the stabilization of phenomena in experimental biology. (shrink)

We outline three very different concepts of the gene—instrumental, nominal, and postgenomic. The instrumental gene has a critical role in the construction and interpretation of experiments in which the relationship between genotype and phenotype is explored via hybridization between organisms or directly between nucleic acid molecules. It also plays an important theoretical role in the foundations of disciplines such as quantitative genetics and population genetics. The nominal gene is a critical practical tool, allowing stable communication between bioscientists (...) in a wide range of fields grounded in well-defined sequences of nucleotides, but this concept does not embody major theoretical insights into genome structure or function. The post-genomic gene embodies the continuing project of understanding how genome structure supports genome function, but with a deflationary picture of the gene as a structural unit. This final concept of the gene poses a significant challenge to conventional assumptions about the relationship between genome structure and function, and between genotype and phenotype. (shrink)

ResumeLa question du filtrage de ľinformation génétique dans la cellule est fondamentale. Comment la cellule sélectionne‐t‐elle, avant de les transformer en RNA puis en protéines, certaines parties bien déterminées de son information génétique? Il ne sera probablement pas possible de donner une explication cohérente du développement embryonnaire, de la différentiation cellulaire et du maintien de ľétat différencie tant que nous n'aurons pas repondu de manière satis‐faisante à cette question.Dans un premier chapitre, quelques notions de base concernant ľexpression génétique sont préséntées. (...) Le dogme de flux de ľinformation génétique dans la cellule, DNARNA protéine est valable à la fois pour les procaryotes et les eucaryotes malgré des différences significatives au niveau de la structure et de la régulation des gènes. Contrairement aux génes procaryotes, la plu‐part des gènes eucaryotes sont morcelés. Le DNA codant pour une protéine est interrompu par des régions non‐codantes dont les transcrits sont éliminés par excision pendant la maturation du RNA messager ultérieurement traduit en protéine. Une grande variété de mécanismes interviennent dans la régulation de ľactivité de ces gènes.Le pouvoir et les limites des méthodes modernes de ľanalyse structurale et fonctionnelle des génes sont discutés dans la deuxième partie de ľarticle. Ľhybridation moléculaire reposant sur la complémentarité des bases azotées des acides nucléiques joue un rôle déterminant dans ľétude de la complexity des génomes et de leur expression. Récemment, ľapplication de la technologie du DNA recombinant et des techniques annexes a permis ľisolement ainsi que la caractérisation de plusieurs génes eucaryotes. La question de ľexpression différentielle de ces génes est actuellement intensément étudiée dans plusieurs systèmes de transcription ayant chacun ses points forts et ses faiblesses.En guise de conclusion, quelques implications de ľessor prodigieux que connaît la génétique moléculaire sont discutées.SummaryThe question of selective expression of genetic information in the cell is fundamental. How does a cell choose particular parts of its genetic information prior to transforming them into RNA and then into proteins? It will probably not be possible to give a coherent explanation of embryonic development, of cell differentiation, and of the maintenance of the differentiated state as until we have answered this question satisfactorily.In the first chapter, several basic notions concerning genetic expression are presented. The central dogma of the flow of genetic information in the cell, DNARNA‐ protein is valid both for prokaryotes and eukaryotes despite significant differences at the level of gene structure and regulation. In contrast to prokaryotic genes, most eukaryotic genes are split. The DNA coding for a protein is interrupted by non‐coding regions whose transcripts are eliminated by excision during the maturation of the messenger RNA which will subsequently be translated into protein. A wide variety of mecanisms are implicated in the regulation of these genes.The scope and limits of modern methods for the structural and functional analyses of genes are discussed in the second part of the article. Molecular hybridization, which is based on the complementarity between the bases of the nucleic acids, plays a key role in the study of the complexity and expression of genes. Recently, the application of recombinant DNA technology and associated techniques has allowed the isolation as well as the characterization of several eukaryotic genes. The question of the differential expression of these genes is currently studied intensively in many transcription systems which all have their strengths and weaknesses.As a conclusion, several implications of the prodigious progress of molecular genetics are discussed.ZusammenfassungDie Frage nach der selektiven Expression der genetischen Information in der Zelle ist fundamental. Wie wählt eine Zelle bestimmte Teile ihrer genetischen Information, um diese dann in RNA und Proteine zu übersetzen? Wahrscheinlich wird es nicht möglich sein, eine vollständige Erklärung für die Embryonalentwicklung, für die Zeildifferenzierung und für di Aufrechterhaltung des differenzierten Zustandes zu geben, bevor wir eine befriedigende Antwort auf diese Frage gefunden haben.Im ersten Kapitel sind mehrere grundlegende Erkenntnisse über die Genexpression dargestellt. Das zentrale Dogma über den Fluss der genetischen Information in der Zelle, DNA RNA Protein, gilt sowohl für Prokaryonten als auch für Eukaryonten trotz bedeutender Unterschiede auf der Ebene der Genstruktur und Genregulation. Im Gegensatz zu den Genen von Prokaryonten sind die meisten Gene der Eukaryonten unterteilt. Die DNA, welche für ein Protein kodiert, ist durch nicht‐kodierende Regionen unterbrochen, welche wahrend des Reifungsprozesses der messenger RNA herausgeschnitten werden. Diese messenger RNA wird schliesslich in ein Protein iibersetzt. Sehr verschiedenartige Mechanismen sind an der Regulation dieser Gene beteiligt.Im zweiten Teil des Artikels werden Ziele und Grenzen moderner Methoden zur Analyse von Struktur und Funktion von Genen diskutiert. Molekulare Hybridisation, welche auf der Komplementarität zwischen den Basen der Nukleinsäuren beruht, spielt eine Schlüsselrolle in der Analyse der Komplexität und Expression der Gene. Die Anwendung der rekombinanten DNA Technologie sowie damit zusammenhängender Methoden hat kürzlich die Isolierung und Charak‐terisierung verschiedener eukaryontischer Gene erlaubt. Die Frage nach der differenziellen Expression dieser Gene wird gegenwärtig mit Hilfe verschiedener Transkriptionssysteme, welche alle ihre Stärken und Schwächen haben, intensiv studiert.Zusammenfassend werden verschiedene Implikationen des gewaltigen Fortschrittes der molekularen Genetik diskutiert. (shrink)

A number of novel gene detection techniques all revolve around the ligation of synthetic nucleic acid probes. In such ligase‐assisted gene detection reactions, specific DNA or RNA sequences are investigated by using them as guides for the covalent joining of pairs of probe molecules. The probes are designed to hybridize immediately next to each other on the target nucleic acid strand. Demonstration of ligated probes results in highly specific detection of and efficient distinction between similar sequence (...) variants under standard reaction conditions. Accordingly, the principle has been applied in automated genetic screening procedures. Ligation reactions are also integral to a number of amplification procedures and they will be of value in an expanding range of genetic analyses. (shrink)

Extracellular nucleic acids are found in different biological fluids in the organism and in the environment: DNA is a ubiquitous component of the organic matter pool in the soil and in all marine and freshwater habitats. Data from recent studies strongly suggest that extracellular DNA and RNA play important biological roles in microbial communities and in higher organisms. DNA is an important component of bacterial biofilms and is involved in horizontal gene transfer. In recent years, the circulating extracellular (...) class='Hi'>nucleic acids were shown to be associated with some diseases. Attempts are being made to develop noninvasive methods of early tumor diagnostics based on analysis of circulating DNA and RNA. Recent observations demonstrated the possibility of nucleic acids exchange between eukaryotic cells and extracellular space suggesting their participation in so far unidentified biological processes. BioEssays 29:654–667, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Enzymes that degrade nucleic acids are emerging as important players in the pathogenesis of inflammatory disease. This is exemplified by the recent identification of four genes that cause the childhood inflammatory disorder, Aicardi‐Goutières syndrome (AGS). This is an autosomal recessive neurological condition whose clinical and immunological features parallel those of congenital viral infection. The four AGS genes encode two nucleases: TREX1 and the hetero‐trimeric Ribonuclease H2 (RNase H2) complex. The biochemical activity of these enzymes was initially characterised 30 years (...) ago but a role in neurological inflammation was entirely unanticipated until they were found to be mutated in AGS. This has led to a hypothesis that accumulation of intracellular nucleic acids occurs as a consequence of mutation in these enzymes and triggers an inflammatory response through activation of innate immune pattern recognition receptors. ©2007 Wiley Periodicals, Inc BioEssays 30:833–842, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Bacteria have a significant impact on human production and life, endangering human life and health, so rapid detection of infectious agents is essential to improve human health. Aptamers, which are pieces of oligonucleotides (DNA or RNA) have been applied to biosensors for bacteria detection due to their high affinity, selectivity, robust chemical stability, and their compatibility with various signal amplification and signal transduction mechanisms. In this review, we summarize the different bacterial aptamers selected in recent years using SELEX technology and (...) discuss the differences in optical and electrochemical bacterial aptamer sensors. In addition the technological developments and innovations in bacterial aptamer sensor technology are introduced. Combining new materials and methods, the efficiency and stability of the sensors have also been improved. This review summarizes the progress of current bacterial aptamer sensors based on their practical application status and provides an outlook on their future development. (shrink)

There is growing evidence of evolutionary genome plasticity. The evolution of repetitive DNA elements, the major components of most eukaryotic genomes, involves the amplification of various classes of mobile genetic elements, the expansion of satellite DNA, the transfer of fragments or entire organellar genomes and may have connections with viruses. In addition to various repetitive DNA elements, a plethora of large and small RNAs migrate within and between cells during individual development as well as during evolution and contribute to changes (...) of genome structure and function. Such migration of DNA and RNA molecules often results in horizontal gene transfer, thus shaping the whole genomic network of interconnected species. Here, we propose that a high evolutionary dynamism of repetitive genome components is often related to the migration/movement of DNA or RNA molecules. We speculate that the cytoplasm is probably an ideal compartment for such evolutionary experiments. (shrink)

In addition to their function in transport of water, ions, small metabolites, and growth factors in normal plant tissue, the plasmodesmata presumably serve as routes for cell‐to‐cell movement of plant viruses in infected tissue. Virus cell‐to‐cell spread through plasmodesmata is an active process mediated by specialized virus encoded movement proteins; however, the mechanism by which these proteins operate is not clear. We incorporate recent information on the biochemical properties of plant virus movement proteins and their interaction with plasmodesmata in a (...) model for transport of nucleic acids through plasmodesmatal channels. We propose that only single stranded (ss) nucleic acids can be transported efficiently through plasmodesmata, and that movement proteins function as molecular chaperones for ss nucleic acids to form unfolded movement protein‐ss nucleic acid complexes. These complexes are targeted to plasmodesmata. Plasmodesmatal permeability is then increased following interaction with movement protein and the entire movement complex or its nucleic acid component is translocated across the plasmodesmatal channel. (shrink)

Structures of multisubunit RNA polymerases strongly differ from the many known structures of single subunit DNA and RNA polymerases. However, in functional complexes of these diverse enzymes, nucleic acids take a similar course through the active center. This finding allows superposition of diverse polymerases and reveals features that are functionally equivalent. The entering DNA duplex is bent by almost 90° with respect to the exiting template–product duplex. At the point of bending, a dramatic twist between subsequent DNA template bases (...) aligns the “coding“ base with the binding site for the incoming nucleoside triphosphate (NTP). The NTP enters through an opening that is found in all polymerases, and, in most cases, binds between an α‐helix and two catalytic metal ions. Subsequent phosphodiester bond formation adds a new base pair to the exiting template–product duplex, which is always bound from the minor groove side. All polymerases may undergo “induced fit” upon nucleic acid binding, but the underlying conformational changes differ. BioEssays 24:724–729, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The central dogma of molecular biology dictates that, with only a few exceptions, information proceeds from DNA to protein through an RNA intermediate. Examining the enigmatic steps from prebiotic to biological chemistry, we take another road suggesting that primordial peptides acted as template for the self-assembly of the first nucleic acids polymers. Arguing in favour of a sort of archaic “reverse translation” from proteins to RNA, our basic premise is a Hadean Earth where key biomolecules such as amino acids, (...) polypeptides, purines, pyrimidines, nucleosides and nucleotides were available under different prebiotically plausible conditions, including meteorites delivery, shallow ponds and hydrothermal vents scenarios. Supporting a protein-first scenario alternative to the RNA world hypothesis, we propose the primeval occurrence of short two-dimensional peptides termed “selective amino acid- and nucleotide-matching oligopeptides” (henceforward SANMAOs) that noncovalently bind at the same time the polymerized amino acids and the single nucleotides dispersed in the prebiotic milieu. In this theoretical paper, we describe the chemical features of this hypothetical oligopeptide, its biological plausibility and its virtues from an evolutionary perspective. We provide a theoretical example of SANMAO’s selective pairing between amino acids and nucleosides, simulating a poly-Glycine peptide that acts as a template to build a purinic chain corresponding to the glycine’s extant triplet codon GGG. Further, we discuss how SANMAO might have endorsed the formation of low-fidelity RNA’s polymerized strains, well before the appearance of the accurate genetic material’s transmission ensured by the current translation apparatus. (shrink)

In this essay, we consider helicases, defined as enzymes that use the free energies of binding and hydrolysis of ATP to drive the unwinding of double‐stranded nucleic acids, and ask how they function within, and are “coupled” to, the macromolecular machines of gene expression. To illustrate the principles of the integration of helicases into such machines, we consider the macromolecular complexes that direct and control DNA replication and DNA‐dependent RNA transcription, and use these systems to illustrate how machines centered (...) around coupled polymerase–helicase systems can be regulated by small changes in the interactions of their functional components. BioEssays 25:1168–1177, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

In human cancers, histone methyltransferase SETDB1 (SET domain, bifurcated 1) is frequently overexpressed but its significance in carcinogenesis remains elusive. A recent study shows that SETDB1 downregulation induces de‐repression of retroelements and innate immunity in cancer cells. The possibility of SETDB1 functioning as a surveillant of retroelement expression is discussed in this study: the cytoplasmic presence of retroelement‐derived nucleic acids (RdNAs) drives SETDB1 into the nucleus by the RNA‐interference route, rendering the corresponding retroelement transcriptionally inert. These RdNAs could, therefore, (...) be signals of genome instability sent out for SETDB1 present in the cytoplasm to maintain genome integrity. (shrink)

The Y‐box proteins are the most evolutionarily conserved nucleic acid binding proteins yet defined in bacteria, plants and animals. The central nucleic acid binding domain of the vertebrate proteins is 43% identical to a 70‐amino‐acid‐long protein (CS7.4) from E. coli. The structure of this domain consists of an antiparallel fivestranded β‐barrel that recognizes both DNA and RNA. The diverse biological roles of these Y‐box proteins range from the control of the E. coli cold‐shock stress response (...) to the translational masking of messenger RNA in vertebrate gametes. This review discusses the organization of the prokaryotic and eukaryotic Y‐box proteins, how they interact with nucleic acids, and their biological roles, both proven and potential. (shrink)

Divergent evolution can explain how many proteins containing structurally similar domains, which perform a variety of related functions, have evolved from a relatively small number of modules or protein domains. However, it cannot explain how protein domains with similar, but distinguishable, functions and similar, but distinguishable, structures have evolved. Examples of this are the RNA‐binding proteins containing the RNA‐binding domain (RBD), and a newly established protein group, the cold‐shock domain (CSD) protein family. Both protein domains contain conserved RNP motifs on (...) similar single‐stranded nucleic acid‐binding surfaces. Apart from the RNP motifs, which have a similar function, the two families show little similarity in topology or amino acid sequence. This can be considered an interesting example of convergent evolution at the molecular level. Previously, a β‐sheet surface was found to interact with RNA in non‐homologous proteins from yeast, phage and man, revealing that this mode of RNA binding may be a widely recurring theme. (shrink)

The series Topics in Current Chemistry presents critical reviews of the present and future trends in modern chemical research. The scope of coverage is all areas of chemical science including the interfaces with related disciplines such as biology, medicine and materials science. The goal of each thematic volume is to give the non-specialist reader, whether in academia or industry, a comprehensive insight into an area where new research is emerging which is of interest to a larger scientific audience. Each review (...) within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years are presented using selected examples to illustrate the principles discussed. The coverage is not intended to be an exhaustive summary of the field or include large quantities of data, but should rather be conceptual, concentrating on the methodological thinking that will allow the non-specialist reader to understand the information presented. Contributions also offer an outlook on potential future developments in the field. Review articles for the individual volumes are invited by the volume editors. Readership: research chemists at universities or in industry, graduate students. (shrink)

Oxidative damage to DNA appears to be a factor in cancer, yet explanations for why highly elevated levels of such lesions do not always result in cancer remain elusive. Much of the genome is non‐coding and lesions in these regions might be expected to have little biological effect, an inference supported by observations that there is preferential repair of coding sequences. RNA has an important coding function in protein synthesis, and yet the consequences of RNA oxidation are largely unknown. Some (...) non‐coding nucleic acid is functional, e.g. promoters, and damage to these sequences may well have biological consequences. Similarly, oxidative damage to DNA may promote microsatellite instability, inhibit methylation and accelerate telomere shortening. DNA repair appears pivotal to the maintenance of genome integrity, and genetic alterations in repair capacity, due to single nucleotide polymorphisms or mutation, may account for inter‐individual differences in cancer susceptibility. This review will survey these aspects of oxidative damage to nucleic acids and their implication for disease. BioEssays 26:533–542, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Flap EndoNuclease‐1 (FEN‐1) is a multifunctional and structure‐specific nuclease involved in nucleic acid processing pathways. It plays a critical role in maintaining human genome stability through RNA primer removal, long‐patch base excision repair and resolution of dinucleotide and trinucleotide repeat secondary structures. In addition to its flap endonuclease (FEN) and nick exonuclease (EXO) activities, a new gap endonuclease (GEN) activity has been characterized. This activity may be important in apoptotic DNA fragmentation and in resolving stalled DNA replication forks. (...) The multiple functions of FEN‐1 are regulated via several means, including formation of complexes with different protein partners, nuclear localization in response to cell cycle or DNA damage and post‐translational modifications. Its functional deficiency is predicted to cause genetic diseases, including Huntington's disease, myotonic dystrophy and cancers. This review summarizes the knowledge gained through efforts in the past decade to define its structural elements for specific activities and possible pathological consequences of altered functions of this multirole player. BioEssays 27:717–729, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

The generation of viral mutants in vitro was demonstrated by treatment of the isolated RNA of Tobacco Mosaic Virus by nitrous acid. This agent causes deaminations converting cytosine into uracil, and adenine into hypoxanthine. Our assay for mutagenesis was the production of local lesions on a tobacco variety on which the untreated strain produces systemic infections only. A variety of different mutants are generated in this way. Quantitative analysis of the kinetics of mutagenesis leads to the conclusion that alteration (...) of a single out of the 6000 nucleotides of the viral RNA is sufficient for causing a mutation. (shrink)

The type-level abstraction is a formal way to represent molecular structures in biological practice. Graphical representations of molecular structures of biological objects are also used to identify functional processes of things. This paper will reveal that category theory is a formal mathematical language not only to visualize molecular structures of biological objects as type-level abstraction formally but also to understand how to infer biological functions from the molecular structures of biological objects. Category theory is a toolkit to understand biological knowledge (...) at the type-level formally, not individual token-level, as well as typical heuristic strategies in molecular biology. (shrink)

Famously, James Watson credited the discovery of the double-helical structure of DNA in 1953 to an X-ray diffraction photograph taken by Rosalind Franklin. Historians of molecular biology have long puzzled over a remarkably similar photograph taken two years earlier by the physicist and pioneer of protein structure William T. Astbury. They have suggested that Astbury’s failure to capitalize on the photograph to solve DNA’s structure was due either to his being too much of a physicist, with too little interest in (...) or knowledge of biology, or to his being misled by an erroneous theoretical model of the gene. Drawing on previously unpublished archival sources, this paper offers a new analysis of Astbury’s relationship to the problem of DNA’s structure, emphasizing a previously overlooked element in Astbury’s thinking: his concept of biological specificity. (shrink)

In this paper, a mathematical model was used to evaluate a dynamical hybrid system for optimizing and controlling the efficacy of plant-based protein in aquafeeds. Fishmeal, raw rapeseed meal, and a fermented meal with yeast and fungi were used as test ingredients for the determination of apparent digestibility coefficients of dry matter, crude protein, crude lipid, energy, and essential amino acids for olive flounder using diets containing 0.5% Cr2O3 as an inert indicator. Among all ingredients tested, FM had the maximum (...) ADC of dry matter, and energy. Fermented meals showed higher ADC. Amino acid digestibility reflects protein digestibility in most cases. Interestingly, protease, lipase, and amylase activities were better expressed in RM-Koji, RM-Yeast, and FM over RM, respectively. The current results deliver important information on nutrients and energy bioavailability in raw and fermented RM, which can be implemented to accurately formulate applied feeds for olive flounder. Compared with other applicable systems, the complexity of the approach implemented has been considerably reduced. (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.

Acid fracturing is the most important stimulation method in the carbonate reservoir. Due to the high cost and high risk of acid fracturing, it is necessary to predict the reservoir productivity before acid fracturing, which can provide support to optimize the parameters of acid fracturing. However, the productivity of a single well is affected by various construction parameters and geological conditions. Overfitting can occur when performing productivity prediction tasks on the high-dimension, small-sized reservoir, and acid (...) fracturing dataset. Therefore, this study developed a stacking heterogeneous ensemble model with a hybrid wrapper-based feature selection strategy to forecast reservoir productivity, resolve the overfitting problem, and improve productivity prediction. Compared to other baseline models, the proposed model was found to have the best predictive performances on the test set and effectively deal with the overfitting. The results proved that the hybrid wrapper-based feature selection strategy introduced in this study reduced data acquisition costs and improved model comprehensibility without reducing model performance. (shrink)

Synthetic biologists try to engineer useful biological systems that do not exist in nature. One of their goals is to design an orthogonal chromosome different from DNA and RNA, termed XNA for xeno nucleic acids. XNA exhibits a variety of structural chemical changes relative to its natural counterparts. These changes make this novel information‐storing biopolymer “invisible” to natural biological systems. The lack of cognition to the natural world, however, is seen as an opportunity to implement a genetic firewall that (...) impedes exchange of genetic information with the natural world, which means it could be the ultimate biosafety tool. Here I discuss, why it is necessary to go ahead designing xenobiological systems like XNA and its XNA binding proteins; what the biosafety specifications should look like for this genetic enclave; which steps should be carried out to boot up the first XNA life form; and what it means for the society at large. (shrink)

The present study examines the physiological alterations in prolactin (PRL) messenger ribonucleic acid (mRNA) and serum PRL levels during the rat estrous cycle and the effed of naloxone, an endogenous opioid peptide receptor antagonist, on PRL gene expression during the rat estrous cycle. Adult female rats exhibiting at least two consecutive 4-day estrous cycles were used in this study. A single injection of naloxone (2mg/kg b.w.) or saline was given sc 30 mm prior to decapitation. Animals were sacrificed at (...) 10:00 h of each stage of the estrous cycle, and at 2-h intervals from 10:00 h to 20:00 h during the proestrus. PRL mRNA and serum PRL levels were determined by an RNA-blot hybridization with the rat PRL cDNA probe and by a PRL radioimmunoassay, respectively. PRL mRNA and serum PRL levels were not dramatically altered in the morning of each stage of diestrus I, II, and proestrus, and naloxone failed to modify the two parameters. During estrus naloxone clearly suppressed serum PRL levels, but it was unable to modify PRL mRNA levels. A more detailed examination of the proestrus stage revealed that PRL mRNA and serum PRL levels fluctuated as a function of time: PRL mRNA levels reached a maximum level at 12:00 h and gradually decreased until 18:00 h. PRL mRNA levels then rose at 20:00 h. No difference in PRL mRNA levels between the control and naloxone-treated groups was observed. Changes in serum PRL level during proestrus were conversely related to changes in PRL mRNA: serum PRL levels were low from 10:00 h to 14:00 h, then increased and reached a maximum level at 16:00-18:00 h. Following then, serum PRL levels were decreased. Naloxone was effective in suppressing the characteristic afternoon surge of PRL from 16:00 h to 20:00 h. These data clearly showed that alterations in PRL mRNA levels were conversely correlated with changes in serum PRL levels on proestrus, indicating differential regulation of PRL gene expression and secretion. (shrink)

Life on earth is bound together by a common heritage, centered around a molecule that is present in almost every living cell of every living creature. Deoxyribonucleic acid (DNA), composed of four base pairs, the nucleic acids thymine, adenine, cytosine, and guanine, encodes the data that directs, in conjunction with the environment, the development and metabolism of all nondependent living creatures. Except for some viruses that rely only on ribonucleic acid (RNA), all living things are built by (...) the interaction of DNA and RNA within cells and their environments. There is no worldwide consensus yet as to whether portions of the human genome should be granted intellectual property protection, as indeed they are in the United States and a number of other nations. DNA posed numerous challenges to the legal framework for patent protection and may suggest developing an entirely new social and legal category recognizing its uniqueness. (shrink)

Basic proteins and nucleic acids are assembled into complexes in a reaction that must be facilitated by nuclear chaperones in order to prevent protein aggregation and formation of non‐specific nucleoprotein complexes. The nucleophosmin/nucleoplasmin (NPM) family of chaperones [NPM1 (nucleophosmin), NPM2 (nucleoplasmin) and NPM3] have diverse functions in the cell and are ubiquitously represented throughout the animal kingdom. The importance of this family in cellular processes such as chromatin remodeling, genome stability, ribosome biogenesis, DNA duplication and transcriptional regulation has led (...) to the rapid growth of information available on their structure and function. The present review covers different aspects related to the structure, evolution and function of the NPM family. Emphasis is placed on the long‐term evolutionary mechanisms leading to the functional diversification of the family members, their role as chaperones (particularly as it pertains to their ability to aid in the reprogramming of chromatin), and the importance of NPM2 as an essential component of the amphibian chromatin remodeling machinery during fertilization and early embryonic development. BioEssays 29: 49–59, 2007. © 2006 Wiley Periodicals, Inc. (shrink)

The universally recognized backbone of molecular biology describes the flow of genetic information from deoxyribonucleic acid (DNA) to ribonucleic acid (RNA) to protein or gene product, that is, DNA is transcribed into another nucleic acid (RNA), which is single stranded, next some types of RNA are in turn translated into proteins. Translation of nucleic acids to proteins is literally a translation from the genomic language to the metabolic language. Codons formed of a sequence of three (...) nucleic acids summon a specific amino acid. Translation from codons to proteins, that is, protein synthesis, takes place by specialized machinery comprising mRNA, ribosomes, and free amino acids. Inferring the structure of DNA opened the door for tremendous advances in understanding the role of genes in creating life, directing replication, and ongoing metabolic processes responsible for maintaining life at both the cellular and organism level. (shrink)

Advocates of an ‘extended evolutionary synthesis’ have claimed that standard evolutionary theory fails to accommodate epigenetic inheritance. The opponents of the extended synthesis argue that the evidence for epigenetic inheritance causing adaptive evolution in nature is insufficient. We suggest that the ambiguity surrounding the conception of the gene represents a background semantic issue in the debate. Starting from Haig’s gene-selectionist framework and Griffiths and Neumann-Held’s notion of the evolutionary gene, we define senses of ‘gene’, ‘environment’, and ‘phenotype’ in a way (...) that makes them consistent with gene-centric evolutionary theory. We argue that the evolutionary gene, when being materialized, need not be restricted to nucleic acids but can encompass other heritable units such as epialleles. If the evolutionary gene is understood more broadly, and the notions of environment and phenotype are defined accordingly, current evolutionary theory does not require a major conceptual change in order to incorporate the mechanisms of epigenetic inheritance. _1_ Introduction _2_ The Gene-centric Evolutionary Theory and the ‘Evolutionary Gene’ _2.1_ The evolutionary gene _2.2_ Genes, phenotypes, and environments _3_ Epigenetic Inheritance and the Gene-Centred Framework _3.1_ Treating the gene as the sole heritable material? _3.2_ Epigenetics and phenotypic plasticity _4_ Conclusion. (shrink)

I present a reconstruction of F.H.C. Crick's two 1957 hypotheses "Sequence Hypothesis" and "Central Dogma" in terms of a contemporary philosophical theory of causation. Analyzing in particular the experimental evidence that Crick cited, I argue that these hypotheses can be understood as claims about the actual difference-making cause in protein synthesis. As these hypotheses are only true if restricted to certain nucleic acids in certain organisms, I then examine the concept of causal specificity and its potential to counter claims (...) about causal parity of DNA and other cellular components. I first show that causal specificity is a special kind of invariance under interventions, namely invariance of generalizations that range over finite sets of discrete variables. Then, I show that this notion allows the articulation of a middle ground in the debate over causal parity. (shrink)

The CRISPR-Cas systems of bacterial and archaeal adaptive immunity have become a household name among biologists and even the general public thanks to the unprecedented success of the new generation of genome editing tools utilizing Cas proteins. However, the fundamental biological features of CRISPR-Cas are of no lesser interest and have major impacts on our understanding of the evolution of antivirus defense, host-parasite coevolution, self versus non-self discrimination and mechanisms of adaptation. CRISPR-Cas systems present the best known case in point (...) for Lamarckian evolution, i.e. generation of heritable, adaptive genomic changes in response to encounters with external factors, in this case, foreign nucleic acids. CRISPR-Cas systems employ multiple mechanisms of self versus non-self discrimination but, as is the case with immune systems in general, are nevertheless costly because autoimmunity cannot be eliminated completely. In addition to the autoimmunity, the fitness cost of CRISPR-Cas systems appears to be determined by their inhibitory effect on horizontal gene transfer, curtailing evolutionary innovation. Hence the dynamic evolution of CRISPR-Cas loci that are frequently lost and acquired by archaea and bacteria. Another fundamental biological feature of CRISPR-Cas is its intimate connection with programmed cell death and dormancy induction in microbes. In this and, possibly, other immune systems, active immune response appears to be coupled to a different form of defense, namely, “altruistic” shutdown of cellular functions resulting in protection of neighboring cells. Finally, analysis of the evolutionary connections of Cas proteins reveals multiple contributions of mobile genetic elements to the origin of various components of CRISPR-Cas systems, furthermore, different biological systems that function by genome manipulation appear to have evolved convergently from unrelated MGE. The shared features of adaptive defense systems and MGE, namely the ability to recognize and cleave unique sites in genomes, make them ideal candidates for genome editing and engineering tools. (shrink)

The present thesis explores some metaphysical issues concerning biochemical kinds and the relations between chemical and biological properties and phenomena. The main result of this thesis is that there is something sui generis about biochemical kinds. This result is motivated by two theoretical steps. The first is characterising biochemical functions as weakly emergent from the chemical structure [Chapter 3, Chapter 6]. The second is via an account for which biochemical kinds are natural categories [Chapter 4, Chapter 7]. The thesis comprises (...) four parts. Part I [Chapter 1, Chapter 2] aims to offer the methodological and conceptual tools that underpin this research. Chapter 1 presents the debate on the unity of science and the motivation of the research. Chapter 2 presents the account of natural kinds that will be used throughout the thesis. Part II [Chapter 3, Chapter 4] offers a detailed metaphysical analysis of the molecular gene. Chapter 3 argues that molecular genes are weakly emergent from nucleic acids. Chapter 4 argues that the category "molecular gene" can be deemed a natural kind, following the account presented in Chapter 2. Part III [Chapter 5, Chapter 6, Chapter 7] explores some of the themes related to biochemical kinds and generalises some of the results from Part II. Chapter 5 considers biochemical functions and how functional attribution should be interpreted for biochemical molecules. Chapter 6 considers the relation between biochemical functions and structure, spelt in terms of weak emergence and explores unity in biochemistry. Chapter 7 considers the topic of biochemical kinds per se and argues that biochemical kinds are natural categories. Part IV [Chapter 8] elucidates the main outcome and the implications that this research can have for future discussion in the philosophy and metaphysics of biochemistry and the unity of science. (shrink)

The “histone code” conjecture of gene regulation is our point of departure for analyzing the interplay between the (quasi)digital script in nucleic acids and proteins on the one hand and the body on the other, between the recorded and organic memory. We argue that the cell’s ability to encode its states into strings of “characters” dramatically enhances the capacity of encoding its experience (organic memory). Finally, we present our concept of interaction between the natural (bodily) world, and the transcendental (...) realm of the digital codes. (shrink)

The concept of genetic information is controversial because it attributes semantic properties to what seem to be ordinary biochemical entities. I argue that nucleic acids contain information in a semantic sense, but only about a limited range of effects. In contrast to other recent proposals, however, I analyze genetic information not in terms of a naturalized account of biological functions, but instead in terms of the way in which molecules determine their products during processes known as template-directed syntheses. I (...) argue that determining an outcome in a certain way is constitutive for being an instruction. On this account, the content of genetic information is identified with the template's properties, which determine the product in the way constitutive for instructions. (shrink)

The genetic code has been regarded as arbitrary in the sense that the codon-amino acid assignments could be different than they actually are. This general idea has been spelled out differently by previous, often rather implicit accounts of arbitrariness. They have drawn on the frozen accident theory, on evolutionary contingency, on alternative causal pathways, and on the absence of direct stereochemical interactions between codons and amino acids. It has also been suggested that the arbitrariness of the genetic code justifies (...) attributing semantic information to macromolecules, notably to DNA. I argue that these accounts of arbitrariness are unsatisfactory. I propose that the code is arbitrary in the sense of Jacques Monod's concept of chemical arbitrariness: the genetic code is arbitrary in that any codon requires certain chemical and structural properties to specify a particular amino acid, but these properties are not required in virtue of a principle of chemistry. This notion of arbitrariness is compatible with several recent hypotheses about code evolution. I maintain that the code's chemical arbitrariness is neither sufficient nor necessary for attributing semantic information to nucleic acids. (shrink)

Autonomous transposable elements, generally considered as junk and selfish, encode transposition proteins that can bind, copy, break, join or degrade nucleic acids as well as process or interact with other proteins. Such a repertoire of activities might be of interest for the host cell. There is indeed substantial evidence that mobile DNA can serve as a dynamic reservoir for new cellular functions. Transposable element genes encoding transposase, integrase, reverse transcriptase as well as structural and envelope proteins have been repeatedly (...) recruited by their host during evolution in most eukaryotic lineages. Such domesticated sequences protect us against infections, are necessary for our reproduction, allow the replication of our chromosomes and control cell proliferation and death; others are essential for plant development. Many new candidates for domesticated sequences have been revealed by sequencing projects. Their functional analysis will uncover new aspects of evolutionary alchemy, the turning of junk into gold within genomes. BioEssays 28: 913–922, 2006. © 2006 Wiley periodicals, Inc. (shrink)