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PubMed1998

A constructionist model predicting the emergence, complementarity and classification of the nucleotide bases.

We are proposing an analytical matrix that models a logical process simulating the emergence of the bases of vital nucleotides. The construction and properties of the matricial model are outlined. The Graph 1 matrix specifies a unique distribution pattern of eight terms coded in binary triplet configurations and obeys specific dynamic laws. The whole set of binary triplet configurations is in dynamic equilibrium. For that reason, it is possible to carry out an analysis by entering by any one of the eight terms on the condition that the operating mode obeys all the internal laws of orientation and symmetries inherent in the matrix. The four chemical elements at the origin of life are distributed following their atomic structures in the order hydrogen (H), carbon (C), nitrogen (N) and oxygen (O) and organized according to the model. The dynamic properties of the model necessitate the running of three successive circular periodic studies per analysis in order to show the emergence of the four bases--adenine, guanine, cytosine and thymine--precisely in that order. The fifth base of the nucleotides--uracil--shows up twice but always in an intermediate position, thus in transition, as it is the case for messenger ribonucleic acid (mRNA). We show also that the model provides for a logical explanation of the law of complementarity of the bases and their chemical classification. It is proposed that subsequent developments of the dynamic laws of this matrix may lead to the study of the logical operations for the formation of protein sequences and of their analysis and to genetic bioprogramming in general. Thus, a strictly logical and dynamic approach to molecular genetics is possible.

Base Sequence↗
PubMed2006

[Physico-chemical determinants of physiOlogical evolution: from protocell to the human].

One of the key physiological problems of evolution is elucidation of the role of environmental inorganic factors in origin of life. A statement is substantiated that a highly significant event in evolution of life was the appearance of protocells with the K cytoplasm in K water reservoirs with their subsequent adaptation to the environment in which Na dominated. This step was accompanied by replacement of the cell envelope with the cell plasma membrane. Precursors of animals' elaborated mechanism of maintenance of the K-cytoplasm with Na-counterkation in the environment. In plants, Na remains a trace element, in animals the Na and K contents are approximately equal, but they are present in different fluid phases. In animals presence of Na+ in the external medium, K+ inside cells has become an initial pre-requisition for electrogenesis and appearance of asymmetrical cells. Electrogenesis of these cells has become a physiological pre-requisition for cell differentiation, the appearance of the nerve cell. Asymmetrical cell has provided development of absorption, digestion, excretion, respiration. Formation of the inner medium has become a prerequisite for establishment of homeostasis. Serum osmolality, sodium concentration, pH, Ca2+ are the most rigidly maintained constants in the blood serum of humans.

Animals↗
PubMed2004

Stepwise evolution of nonliving to living chemical systems.

Steps by which a nonliving chemical system could have transformed into a living system are described and discussed, assuming general features of Wächtershäuser's chemo-autotrophic surface theory of the origin of life. Environmental species such as CO2 and H2S are proposed to have reacted to form a quasi-steady state metal-bound intermediate (CH3-M) that slowly decayed into waste (CH4). Unpredictable dispersive reactions expanded the system to include surface-bound forms of the citric acid cycle intermediates (oxaloacetate-->citrate). Further reaction yielded an autocatalytic system in which raw materials are converted into the system at exponential rates. Combinatorial dispersive reactions that improved the performance of this system were automatically selected and incorporated into it. Systems evolved critical features of living systems (proteins, membranes, proteins, nucleic acids, etc.) using two related mechanisms called grafting and waste-conversion. Such living systems were transformed from less recognizable types (characterized by autocatalytic spreading, decentralization, poorly defined boundaries, etc.) into more recognizable ones (encapsulated by membranes, controlled by single-molecule genomes, etc.) that self-replicated by a cell division cycle and could evolve by the standard gene-based Darwinian mechanism. The resulting systems are viewed as having an autocatalytic network composed of three linked autocatalytic subreactions.

Cell Cycle↗
PubMed1997

Surprising fidelity of template-directed chemical ligation of oligonucleotides.

BACKGROUND: Nucleic acid replication via oligonucleotide ligation has been shown to be extremely prone to errors. If this is the case, it is difficult to envision how the assembly and replication of short oligonucleotides could have contributed to the origin of life and to the evolution of a putative RNA world. In order to assess the fidelity of oligonucleotide replication more accurately, chemical ligation reactions were performed with constant-sequence DNA templates and random-sequence DNA pools as substrates. RESULTS: In keeping with earlier results, constant-sequence hairpin templates were not faithfully copied by random-sequence substrates. Linear templates, however, showed exceptional replication fidelity, particularly when random hexamers were ligated at 25 degrees C. Surprisingly, at low temperatures the formation of G.A base pairs was common and sometimes occurred even more readily than the formation of the corresponding Watson-Crick A-T and G-C base pairs. CONCLUSIONS: The fidelity of ligation reactions increases with temperature and decreases with the length of the random-sequence substrates. Oligonucleotides with a defined sequence can be copied faithfully in the absence of enzymes. Thus, to the extent that short oligonucleotides could readily have been generated by prebiotic mechanisms, it is possible that the earliest self-replicators arose via oligonucleotide ligation.

Base Composition↗
PubMed1993

Prebiotic ammonia from reduction of nitrite by iron (II) on the early Earth.

Theories for the origin of life require the availability of reduced (or 'fixed') nitrogen-containing compounds, in particular ammonia. In reducing atmospheres, such compounds are readily formed by electrical discharges, but geochemical evidence suggests that the early Earth had a non-reducing atmosphere, in which discharges would have instead produced NO. This would have been converted into nitric and nitrous acids and delivered to the early oceans as acid rain. It is known, however, that Fe(II) was present in the early oceans at much higher concentrations than are found today, and thus the oxidation of Fe(II) to Fe(III) provides a possible means for reducing nitrites and nitrates to ammonia. Here we explore this possibility in a series of experiments which mimic a broad range of prebiotic seawater conditions (the actual conditions on the early Earth remain poorly constrained). We find that the reduction by Fe(II) of nitrites and nitrates to ammonia could have been a significant source of reduced nitrogen on the early Earth, provided that the ocean pH exceeded 7.3 and is favoured for temperatures greater than about 25 degrees C.

Ammonia↗
PubMed1997

Substrate-directed formation of small biocatalysts under prebiotic conditions.

One of the most debated issues concerning the origin of life, is how enzymes which are essential for existence of any living organism, evolved. It is clear that, regardless of the exact mechanism, the process should have been specific and reproducible, involving interactions between different molecules. We propose that substrate templating played a crucial role in maintaining reproducible and specific formation of prebiotic catalysts. This work demonstrates experimentally, for the first time, substrate-directed formation of an oligopeptide that possesses a specific catalytic activity toward the substrate on which it was formed. In our experiments we used the substrate O-nitrophenol-beta-D-galactopyranoside (ONPG) as a molecular template for the synthesis of a specific catalyst that is capable of cleaving the same substrate. This was achieved by incubation of the substrate with free amino acids and a condensing agent (dicyandiamide) at elevated temperatures. A linear increase with time of the reaction rate (d[product]/d2t), pointed to an acceleration regime, where the substrate generates the formation of the catalyst. The purified catalyst, produced by a substrate-directed mechanism, was analyzed, and identified as Cys2-Fe+2. The mechanism of substrate-directed formation of prebiotic catalysts provides a solution to both the specificity and the reproducibility requirements from any prebiotic system which should evolve into the biological world.

Amino Acids↗
PubMed1988

Prebiotic ribose synthesis: a critical analysis.

The discovery of catalytic ability in RNA has given fresh impetus to speculations that RNA played a critical role in the origin of life. This question must rest on the plausibility of prebiotic oligonucleotide synthesis, rather than on the properties of the final product. Many claims have been published to support the idea that the components of RNA were readily available on the prebiotic earth. In this article, the literature cited in support of the prebiotic availability of one subunit, D-ribose, is reviewed to determine whether it justifies the claim. Polymerization of formaldehyde (the formose reaction) has been the single reaction cited for prebiotic ribose synthesis. It has been conducted with different catalysts: numerous basic substances, neutral clays and heat, and various types of radiation. Ribose has been identified (yields are uncertain, but unlikely to be greater than 1%) in reactions run with concentrated (0.15 M or greater) formaldehyde. It has been claimed in reactions run at lower concentration, but characterization has been inadequate, and experimental details have not been provided. The complex sugar mixture produced in the formose reaction is rapidly destroyed under the reaction conditions. Nitrogenous substances (needed for prebiotic base synthesis) would interfere with the formose reaction by reacting with formaldehyde, the intermediates, and sugar products in undesirable ways. The evidence that is currently available does not support the availability of ribose on the prebiotic earth, except perhaps for brief periods of time, in low concentration as part of a complex mixture, and under conditions unsuitable for nucleoside synthesis.

Catalysis↗
PubMed2006

Glyoxylate as a backbone linkage for a prebiotic ancestor of RNA.

The origin of the first RNA polymers is central to most current theories for the origin of life. Difficulties associated with the prebiotic formation of RNA have lead to the general consensus that a simpler polymer preceded RNA. However, polymers proposed as possible ancestors to RNA are not much easier to synthesize than RNA itself. One particular problem with the prebiotic synthesis of RNA is the formation of phosphoester bonds in the absence of chemical activation. Here we demonstrate that glyoxylate (the ionized form of glyoxylic acid), a plausible prebiotic molecule, represents a possible ancestor of the phosphate group in modern RNA. Although in low yields ( approximately 1%), acetals are formed from glyoxylate and nucleosides under neutral conditions, provided that metal ions are present (e.g., Mg2+), and provided that water is removed by evaporation at moderate temperatures (e.g., 65 degrees C), i.e. under "drying conditions". Such acetals are termed ga-dinucleotides and possess a linkage that is analogous to the backbone in RNA in both structure and electrostatic charge. Additionally, an energy-minimized model of a gaRNA duplex predicts a helical structure similar to that of A-form RNA. We propose that glyoxylate-acetal linkages would have had certain advantages over phosphate linkages for early self-replicating polymers, but that the distinct functional properties of phosphoester and phosphodiester bonds would have eventually lead to the replacement of glyoxylate by phosphate.

Chromatography, High Pressure Liquid↗
PubMed2002

Origins of gene, genetic code, protein and life: comprehensive view of life systems from a GNC-SNS primitive genetic code hypothesis.

We have investigated the origin of genes, the genetic code, proteins and life using six indices (hydropathy, alpha-helix, beta-sheet and beta-turn formabilities, acidic amino acid content and basic amino acid content) necessary for appropriate three-dimensional structure formation of globular proteins. From the analysis of microbial genes, we have concluded that newly-born genes are products of nonstop frames (NSF) on antisense strands of microbial GC-rich genes [GC-NSF(a)] and from SNS repeating sequences [(SNS)n] similar to the GC-NSF(a) (S and N mean G or C and either of four bases, respectively). We have also proposed that the universal genetic code used by most organisms on the earth presently could be derived from a GNC-SNS primitive genetic code. We have further presented the [GADV]-protein world hypothesis of the origin of life as well as a hypothesis of protein production, suggesting that proteins were originally produced by random peptide formation of amino acids restricted in specific amino acid compositions termed as GNC-, SNS- and GC-NSF(a)-0th order structures of proteins. The [GADV]-protein world hypothesis is primarily derived from the GNC-primitive genetic code hypothesis. It is also expected that basic properties of extant genes and proteins could be revealed by considerations based on the scenario with four stages.

Amino Acids↗
PubMed2006

The origin of replicators and reproducers.

Replicators are fundamental to the origin of life and evolvability. Their survival depends on the accuracy of replication and the efficiency of growth relative to spontaneous decay. Infrabiological systems are built of two coupled autocatalytic systems, in contrast to minimal living systems that must comprise at least a metabolic subsystem, a hereditary subsystem and a boundary, serving respective functions. Some scenarios prefer to unite all these functions into one primordial system, as illustrated in the lipid world scenario, which is considered as a didactic example in detail. Experimentally produced chemical replicators grow parabolically owing to product inhibition. A selection consequence is survival of everybody. The chromatographized replicator model predicts that such replicators spreading on surfaces can be selected for higher replication rate because double strands are washed away slower than single strands from the surface. Analysis of real ribozymes suggests that the error threshold of replication is less severe by about one order of magnitude than thought previously. Surface-bound dynamics is predicted to play a crucial role also for exponential replicators: unlinked genes belonging to the same genome do not displace each other by competition, and efficient and accurate replicases can spread. The most efficient form of such useful population structure is encapsulation by reproducing vesicles. The stochastic corrector model shows how such a bag of genes can survive, and what the role of chromosome formation and intragenic recombination could be. Prebiotic and early evolution cannot be understood without the models of dynamics.

Biological Evolution↗
PubMed2006

Abiotic condensation synthesis of glyceride lipids and wax esters under simulated hydrothermal conditions.

Precursor compounds for abiotic proto cellular membranes are necessary for the origin of life. Amphipathic compounds such as fatty acids and acyl glycerols are important candidates for micelle/bilayer/vesicle formation. Two sets of experiments were conducted to study dehydration reactions of model lipid precursors in aqueous media to form acyl polyols and wax esters, and to evaluate the stability and reactions of the products at elevated temperatures. In the first set, mixtures of n-nonadecanoic acid and ethylene glycol in water, with and without oxalic acid, were heated at discrete temperatures from 150 ( composite function)C to 300 ( composite function)C for 72 h. The products were typically alkyl alkanoates, ethylene glycolyl alkanoates, ethylene glycolyl bis-alkanoates and alkanols. The condensation products had maximum yields between 150 ( composite function)C and 250 ( composite function)C, and were detectable and thus stable under hydrothermal conditions to temperatures < 300 ( composite function)C. In the second set of experiments, mixtures of n-heptanoic acid and glycerol were heated using the same experimental conditions, with and without oxalic acid, between 100 ( composite function)C and 250 ( composite function)C. The main condensation products were two isomers each of monoacylglycerols and diacylglycerols at all temperatures, as well as minor amounts of the fatty acid anhydride and methyl ester. The yield of glyceryl monoheptanoates generally increased with increasing temperature and glyceryl diheptanoates decreased noticeably with increasing temperature. The results indicate that condensation reactions and abiotic synthesis of organic lipid compounds under hydrothermal conditions occur easily, provided precursor concentrations are sufficiently high.

Esters↗
PubMed2006

Protocell-like microspheres from thermal polyaspartic acid.

One of the most prominent amino acids to appear in monomer-generating origin-of-life experiments is aspartic acid. Hugo Schiff found in 1897 that aspartic acid polymerizes when heated to form polyaspartylimide which hydrolyzes in basic aqueous solution to form thermal polyaspartic acid which is a branched polypeptide. We recently reported at the ISSOL 2005 Conference that commercially made thermal polyaspartic acid forms microspheres when heated in boiling water and allowed to cool. In a new experiment we heated aspartic acid at 180 degrees C for up to 100 h to form thermal polyaspartylimide which when heated in boiling water without addition of base hydrolyzed to form thermal polyaspartic acid which upon cooling formed microspheres. Thermal polyaspartic acid microspheres appear protocell-like in the sense of being prebiotically plausible lattices or containers that could eventually have been filled with just the right additions of primordial proteins, nucleic acids, lipids, and metabolites so as to constitute protocells capable of undergoing further chemical and biological evolution. Thermal polyaspartic acid microspheres are extremely simple models of protocells that are more amenable to precise quantitative experimental investigation than the proteinoid microspheres of Sidney W. Fox. We present here scanning electron microscope images of such thermal polyaspartic acid microspheres. Figure 1 shows thermal polyaspartic acid microspheres from L: -aspartic acid heated at 180 degrees C for 50 h, at a magnification of 3,500x. Figure 2 shows thermal polyaspartic acid microspheres from the same sample at a magnification of 7,000x. The thermal polyaspartic acid microspheres have a diameter of approximately 1 mum These images were viewed with a Hitachi S2460N scanning electron microscope at 20 kV acceleration voltage. Figure 1 Thermal polyaspartic acid microspheres from L: -aspartic acid heated at 180 degrees C for 50 h, at a magnification of 3,500x. Figure 2 Thermal polyaspartic acid microspheres from L: -aspartic acid heated at 180 degrees C for 50 h, at a magnification of 7,000x.

Evolution, Chemical↗
PubMed2004

Chronic pelvic pain of bladder origin: epidemiology, pathogenesis and quality of life.

Interstitial cystitis (IC) is chronic pelvic pain of bladder origin that is far more common than previously thought. Although prevalence estimates vary greatly, studies consistently indicate that IC affects approximately 20% of women. The pathogenesis remains unknown but is thought to be multifactorial. Many women with IC have an abnormality of the bladder surface; ongoing exposure to urine solutes permeates the urothelium and causes significant pain and inflammation. The increased number of C-fibers and increased amount of substance P found in IC patients also contribute to the inflammation and pain associated with this condition. Long-standing and/or severe disease significantly impairs the ability to work and quality of life among IC patients. The physical and psychological consequences of IC should be a "call to arms" for clinicians to promptly and accurately diagnose and manage IC.

Chronic Disease↗
PubMed2001

Why is DNA damage signaling so complicated? Chaos and molecular signaling.

Molecular signaling in eukaryotic cells is accomplished by complex and redundant pathways converging on key molecules that are allosterically controlled by a limited number of signaling proteins. The p53-signaling pathway is an example of a complicated sequence of signals produced in response to DNA damage. This pattern of signaling may arise from chance occurrences at the origin of life and the necessities imposed on a nanomolar system. From this viewpoint, chaos theory may explain the origin, complexity, and convergence of these pathways.

Animals↗
PubMed2004

A sulfur-based survival strategy for putative phototrophic life in the venusian atmosphere.

Several observations indicate that the cloud deck of the venusian atmosphere may provide a plausible refuge for microbial life. Having originated in a hot proto-ocean or been brought in by meteorites from Earth (or Mars), early life on Venus could have adapted to a dry, acidic atmospheric niche as the warming planet lost its oceans. The greatest obstacle for the survival of any organism in this niche may be high doses of ultraviolet (UV) radiation. Here we make the argument that such an organism may utilize sulfur allotropes present in the venusian atmosphere, particularly S(8), as a UV sunscreen, as an energy-converting pigment, or as a means for converting UV light to lower frequencies that can be used for photosynthesis. Thus, life could exist today in the clouds of Venus.

Atmosphere↗
PubMedDate not supplied

Laryngeal ventricle. Historical features.

The author reviews some of the salient historical features related to the anatomical description of the laryngeal ventricle and its saccule. The paper is based on a translation of Morgagni's original work published in 1719. This information is presented along with a short biographical note of Morgangni's life. Only original sources were used and photographs of the original illustrations are included.

History, 18th Century↗
PubMedDate not supplied

Carbonaceous meteorites as a source of sugar-related organic compounds for the early Earth.

The much-studied Murchison meteorite is generally used as the standard reference for organic compounds in extraterrestrial material. Amino acids and other organic compounds important in contemporary biochemistry are thought to have been delivered to the early Earth by asteroids and comets, where they may have played a role in the origin of life. Polyhydroxylated compounds (polyols) such as sugars, sugar alcohols and sugar acids are vital to all known lifeforms-they are components of nucleic acids (RNA, DNA), cell membranes and also act as energy sources. But there has hitherto been no conclusive evidence for the existence of polyols in meteorites, leaving a gap in our understanding of the origins of biologically important organic compounds on Earth. Here we report that a variety of polyols are present in, and indigenous to, the Murchison and Murray meteorites in amounts comparable to amino acids. Analyses of water extracts indicate that extraterrestrial processes including photolysis and formaldehyde chemistry could account for the observed compounds. We conclude from this that polyols were present on the early Earth and therefore at least available for incorporation into the first forms of life.

Carbohydrates↗
PubMed1994

Adjustment issues with adult children of alcoholics.

The current study assessed locus of control, general level of life satisfaction, and self-reported grade-point averages among adults who had experienced either alcoholism within the family of origin, traumatic life events other than alcoholism, or who indicated neither problem during their childhood. Results indicated that both the adult children of alcoholics (ACOA) and traumatic experience (TE) groups had lower life satisfaction scores than the control group. Significantly lower levels of locus of control also were found for the ACOA group in comparison to the control group. There were no significant differences among the three groups based on self-reported GPAs. Results of the current study support the concept that family dysfunction during childhood can influence negatively later life experiences and adjustment.

Activities of Daily Living↗