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PubMed1987

Nucleotide sequence and organization of the human S-protein gene: repeating peptide motifs in the "pexin" family and a model for their evolution.

The S-protein/vitronectin gene was isolated from a human genomic DNA library, and its sequence of about 5.3 kilobases including the adjacent 5' and 3' flanking regions was established. Alignment of the genomic DNA nucleotide sequence and the cDNA sequence indicated that the gene consisted of eight exons and seven introns. The intron positions in the S-protein gene and their phase type were compared to those in the hemopexin gene which shares amino acid sequence homologies with transin and the S-protein. Three introns have been found at equivalent positions; two other introns are very close to these positions and are interpreted as cases of intron sliding. Introns 3-7 occur at a conserved glycine residue within repeating peptide segments, whereas introns 1 and 2 are at the boundaries of the Somatomedin B domain of S-protein. The analysis of the exon structure in relation to repeating peptide motifs within the S-protein strongly suggests that it contains only seven repeats, one less than the hemopexin molecule. A very similar repeat pattern like that in hemopexin is shown to be present also in two other related proteins, transin and interstitial collagenase. An evolutionary model for the generation of the repeat pattern in the S-protein and the other members of this novel "pexin" gene family is proposed, and the sequence modifications for some of the repeats during divergent evolution are discussed in relation to known unique functional properties of hemopexin and S-protein.

Amino Acid Sequence↗
PubMed2006

Genetic architecture of the cryptic species complex of Acanthocyclops vernalis (Crustacea: Copepoda). II. Crossbreeding experiments, cytogenetics, and a model of chromosomal evolution.

Collectively, populations of Acanthocyclops vernalis, a species complex of freshwater copepods, are remarkably similar as to morphology and DNA content, despite variability in chromosome number. Reproductive isolation had been reported among some populations, but with each new investigation the species boundaries and factors that may influence them appeared less clear. To clarify the pattern of biological species within this group of populations, we adopted a comprehensive approach and examined patterns of reproductive isolation in populations for which morphology, chromosome number, DNA content, and 18S rDNA sequences are known. In this study we established nine isofemale lines from four sites in Wisconsin and performed 266 crosses. Crosses within and among these lines were used to relate the degree of reproductive isolation to chromosome differences and to construct a model to explain the origin and maintenance of chromosome number variability. Different gametic and somatic chromosome numbers were observed among specimens within some isofemale lines. In a few cases, gametes with different haploid numbers were produced by a single female. Matings within isofemale lines always produced at least some reproductively successful replicate crosses (produced viable, fertile offspring). Crosses between lines from the same site showed reduced success relative to within-line crosses. Crosses between populations from distant sites showed limited genetic compatibility, producing viable, fertile F1 offspring but infertile F2 adults. One cross between lines with different chromosome numbers (one with 2n = 8 and one with 2n = 10) produced fertile viable offspring, which reproduced for at least 60 generations. These hybrids had either eight or nine chromosomes in the third generation of inbreeding, and eight chromosomes after 20 generations. These hybrids also had reduced nuclear DNA contents at the third generation, a level that persisted through the 20th generation. Successful backcrosses between some hybrids and their parental lines further demonstrated the potential for genetic compatibility among forms with different chromosome numbers. We propose a model in which alterations due to Robertsonian fusions, translocations, and/or loss of chromosomal fragments generate heritable variation, only some of which leads to reproductive isolation. Hence, some of the criteria traditionally used to recognize species boundaries in animals (morphology, DNA content, chromosome number) may not apply to this species complex.

Animals↗
PubMed1990

Gene structure of nuclear lamin LIII of Xenopus laevis; a model for the evolution of IF proteins from a lamin-like ancestor.

The lamin LIII gene of Xenopus laevis has been characterized. The gene is duplicated in the Xenopus genome. The transcribed region spreads over 22 kb of genomic DNA encoding 12 exons. Two alternatively spliced mRNAs are observed which encode LIII isoforms that differ only by the 12 C-terminal amino acids which, however, both contain the CaaX motif known to be the target of post-translational modifications. The intron pattern of the lamin LIII gene is strikingly similar to that of an invertebrate intermediate filament (IF) gene over the entire protein coding sequence. The similarity in gene structure is restricted to the rod domain when compared with vertebrate types I-III IF genes. Our data suggest a model of how IF proteins evolved from a lamin-like ancestor by deletion of two signal sequences; the nuclear localization signal and the C-terminal ras-related CaaX motif. The data rule out the previously proposed hypothesis that IF proteins evolved from an intronless ancestor with an early divergence of neuronal and non-neuronal IF proteins. Together with the data presented in the accompanying paper by Dodemond et al. it can be concluded that the tail domains of lamins and invertebrate IF proteins, but not those of vertebrate IF proteins, are homologous. Thus, the different vertebrate IF proteins probably evolved by combination of the central rod domain with different tail domains by exon shuffling.

Amino Acid Sequence↗
PubMed2002

Magnetization evolution in network models of porous rock under conditions of drainage and imbibition.

Surface-enhanced relaxation of nuclear magnetization in fully and partially saturated water-wet porous media is studied using a pore network simulator. The simulator is based on a description of the pore space in terms of a regular cubic lattice of pores and throats following respective size distributions. The latter are obtained from geometric characterization of 3D stochastic replicas of real porous rock samples. Concepts of percolation theory are used to simulate the pore-scale distribution of a strongly wetting phase under conditions of quasistatic drainage by or imbibition against a nonwetting phase. The results of these simulations compare favorably with experimental mercury intrusion/retraction curves. The equations governing magnetization evolution in a connected pore system are then solved by matrix diagonalization for different values of wetting-phase saturation along the primary drainage and secondary imbibition paths. Analysis of the corresponding spectra of decay rates provides new insights regarding the influence of pore structure (pore and throat size distributions, spatial correlation), surface relaxation strength, and fluid distribution on diffusive coupling between pores. For pore and throat size distributions and surface relaxation strength representative of sandstones, diffusive coupling is quite important, especially under conditions of partial saturation. Remarkably, simulations show that correlated heterogeneity is the main reason pores appear poorly coupled with respect to NMR relaxation-an assumption underlying the correspondence between pore size and relaxation time distributions. Finally, for a given value of wetting-phase saturation, the history of saturation change (drainage or imbibition) is shown to have a profound effect on the spectrum of decay rates.

Journal Article↗
PubMed2004

A model for karyotypic evolution in testicular germ cell tumors.

Testicular germ cell tumor karyotypes are characterized by near-triploidy, with chromosome numbers ranging from 50 to 70, and by the frequent appearance of i(12p). The high chromosome number has been attributed to the formation of tetraploid carcinoma in situ cells followed by chromosomal losses that ultimately lead to tumor forms that are more advanced. In the present investigation, we show by analysis of the accumulated cytogenetic data on testicular germ cell tumors and computer simulations that two distinct processes are operating in the karyotypic evolution of these tumors. The results suggest that whole-chromosome changes originate from a multipolar cell division of a tetraploid cell, whereas imbalances caused by structural changes accumulate in a stepwise manner.

Cell Division↗
PubMed2006

Ripples in a pond: an open system model of the evolution of safety culture.

The development of an effective safety culture is essential to promote safe operations. Previous studies have either identified the characteristics of effective safety culture analytically, inferring them from signs and symbols derived from working practices, or have restricted the study of the development of safety culture to workers within an organisation. This paper describes a large-scale survey-based study in which the factors influencing the evolution of safety culture are identified empirically and, drawing upon open systems theory, are also extended beyond the bounds of the organisation. Three major determinants of safety culture are identified: safety concerns, influences and actions. Sub-components within each of these categories are also identified and the relationship between them is hypothesised.

Adult↗
PubMed2025

Multi-scale phylodynamic modelling of rapid punctuated pathogen evolution.

Computational multi-scale pandemic modelling remains a major and timely challenge. Here we identify specific requirements for a new class of models simulating pandemics across three scales: (1) pathogen evolution, often punctuated by the rapid emergence of new variants, (2) human interactions within a heterogeneous population, and (3) public health responses which constrain individual actions to control the disease transmission. We then present a pandemic modelling framework satisfying these requirements and capable of simulating feedback loops between dynamics unfolding at these different scales. The developed framework comprises a stochastic agent-based model of pandemic spread, coupled with a phylodynamic model that incorporates within-host pathogen evolution. It is validated with a case study, modelling the punctuated evolution of SARS-CoV-2, based on global and contemporary genomic surveillance data, which captures a large heterogeneous population. We demonstrate that the model replicates the essential features of the COVID-19 pandemic and virus evolution, while retaining computational tractability and scalability.

SARS-CoV-2↗
PubMed1985

Structural organization of the human kininogen gene and a model for its evolution.

The entire human kininogen gene has been isolated as a set of overlapping genomic DNA fragments, and the 11 exons encompassing approximately 27 kilobase pairs have been mapped by restriction enzyme analysis and nucleotide sequence determination. The nine 5'-terminal exons encode the 5'-untranslated region and the protein-coding region for the signal peptide and the heavy chain, which are common for high molecular weight (HMW) and low molecular weight (LMW) prekininogen mRNAs. Exon 10 consists of the common sequence for bradykinin and the immediately following unique sequence for HMW prekininogen mRNA. Exon 11 is then located following a 90-nucleotide sequence downstream from exon 10 and precisely specifies the sequence unique to LMW prekininogen mRNA. This, together with the hybridization analysis of total human cellular DNA, leads us to conclude that human HMW and LMW prekininogen mRNAs are produced from a single gene as a consequence of alternative RNA processing events. The structural analysis of the kininogen gene also shows that each of the nine 5'-terminal exons discretely specifies the nine protein domains observed in the amino-terminal portion of the kininogens. Furthermore, these nine genetic domains can be characterized by a thrice repeated pattern of three genetic segments, and two sets of these three domains, encompassing exons 3-5 and exons 6-8, are most closely related to each other. Therefore, we have proposed two successive duplication mechanisms as a model for the generation of the structure of the kininogen gene.

Base Sequence↗
PubMed2006

Effect of suddenly turning on interactions in the Luttinger model.

The evolution of correlations in the exactly solvable Luttinger model (a model of interacting fermions in one dimension) after a suddenly switched-on interaction is analytically studied. When the model is defined on a finite-size ring, zero-temperature correlations are periodic in time. However, in the thermodynamic limit, the system relaxes algebraically towards a stationary state which is well described, at least for some simple correlation functions, by the generalized Gibbs ensemble recently introduced by Rigol et al. (cond-mat/0604476). The critical exponent that characterizes the decay of the one-particle correlation function is different from the known equilibrium exponents. Experiments for which these results can be relevant are also discussed.

Journal Article↗
PubMed1985

Models of molecular evolution. 2. Stereospecificity of dipeptide syntheses by means of cyanamides and carbodiimides.

Acetyl, benzyloxycarbonyl and tosyl protected DL-alanine, DL-leucine, DL-methionine, DL-phenylalanine, and DL-valine were condensed with DL-amino acid methyl esters. Cyanamide, diethylcyanamide, diisopropyl carbodiimide, dicyclohexyl carbodiimide, and N-cyclohexyl-N'-(2-morpholino ethyl) carbodiimide-N''-methotosylate served as condensing reagents. Water, methanol, and dimethylformamide were used as reaction media. The stereochemical course of these dipeptide syntheses was elucidated by means of 13C-n.m.r. spectroscopy. The formation of L-L and D-D bonds (isotactic sequences) was favoured in ca. 80% of all condensations. L-L/L-D (D-D/D-L) ratios of up to 6:1 were found.

Dipeptides↗
PubMed1996

MCF10AT: a model for the evolution of cancer from proliferative breast disease.

A human cell line (MCF10A) originated from spontaneous immortalization of breast epithelial cells obtained from a patient with fibrocystic disease. MCF10A cells do not survive in vivo in immunodeficient mice. However, T24 c-Ha-ras oncogene-transfected MCF10A cells (MCF10AT) form small nodules in nude/beige mice that persist for at least 1 year and sporadically progress to carcinomas. By reestablishing cells in tissue culture from one of the carcinomas, a cell line designated MCF10AT1 was derived that forms simple ducts when transplanted in Matrigel into immunodeficient mice. With time in vivo, the epithelium becomes proliferative and a cribriform pattern develops within the xenografts. A significant number progress to lesions resembling atypical hyperplasia and carcinoma in situ in women, and approximately 25% progress to invasive carcinomas with various types of differentiation including glandular, squamous, and undifferentiated. Cells have been established in culture from lesions representing successive transplant generations. With each generation, cells are somewhat more likely to progress to high risk lesions resembling human proliferative breast disease. Although the incidence of invasive carcinoma remained fairly constant at 20 to 25%, the frequency of nodules showing proliferative breast disease rose from 23% in the first transplant generation to 56% in the fourth transplant generation.

Animals↗
PubMed1994

Malate dehydrogenase: a model for structure, evolution, and catalysis.

Malate dehydrogenases are widely distributed and alignment of the amino acid sequences show that the enzyme has diverged into 2 main phylogenetic groups. Multiple amino acid sequence alignments of malate dehydrogenases also show that there is a low degree of primary structural similarity, apart from in several positions crucial for nucleotide binding, catalysis, and the subunit interface. The 3-dimensional structures of several malate dehydrogenases are similar, despite their low amino acid sequence identity. The coenzyme specificity of malate dehydrogenase may be modulated by substitution of a single residue, as can the substrate specificity. The mechanism of catalysis of malate dehydrogenase is similar to that of lactate dehydrogenase, an enzyme with which it shares a similar 3-dimensional structure. Substitution of a single amino acid residue of a lactate dehydrogenase changes the enzyme specificity to that of a malate dehydrogenase, but a similar substitution in a malate dehydrogenase resulted in relaxation of the high degree of specificity for oxaloacetate. Knowledge of the 3-dimensional structures of malate and lactate dehydrogenases allows the redesign of enzymes by rational rather than random mutation and may have important commercial implications.

Amino Acid Sequence↗
PubMed1993

A protein alignment scoring system sensitive at all evolutionary distances.

Protein sequence alignments generally are constructed with the aid of a "substitution matrix" that specifies a score for aligning each pair of amino acids. Assuming a simple random protein model, it can be shown that any such matrix, when used for evaluating variable-length local alignments, is implicitly a "log-odds" matrix, with a specific probability distribution for amino acid pairs to which it is uniquely tailored. Given a model of protein evolution from which such distributions may be derived, a substitution matrix adapted to detecting relationships at any chosen evolutionary distance can be constructed. Because in a database search it generally is not known a priori what evolutionary distances will characterize the similarities found, it is necessary to employ an appropriate range of matrices in order not to overlook potential homologies. This paper formalizes this concept by defining a scoring system that is sensitive at all detectable evolutionary distances. The statistical behavior of this scoring system is analyzed, and it is shown that for a typical protein database search, estimating the originally unknown evolutionary distance appropriate to each alignment costs slightly over two bits of information, or somewhat less than a factor of five in statistical significance. A much greater cost may be incurred, however, if only a single substitution matrix, corresponding to the wrong evolutionary distance, is employed.

Algorithms↗
PubMed1986

Satellite DNA in the three C-bands of an unusual mouse marker chromosome. A model of chromosomal evolution.

A marker chromosome in the stemline of a new murine cell line is described on the basis of different stainings and in situ hybridization. The marker was characterized originally by three C-bands, one from each centromeric region of the three chromosomes constituting the marker. In the course of stemline evolution, two of the C-bands have been lost and the marker has developed into a monocentric chromosome, phenotypically and functionally normal.

Animals↗
PubMed1991

Avian trypanosomes as models of hemoflagellate evolution.

In the 15 years since the last review on avian trypanosomes(1), there has been a steady accrual of information on the distribution and dynamics of trypanosome infections in wild bird populations. Recent immunological and biochemical studies provide evidence that several trypanosome species can parasitize an ecological guild of host species but the relative roles of avian host phylogeny and vector ecology remain unanswered. In this article, Victor Apanius reviews the habitat preferences and behavior of trypanosomes within the avian host and attempts to draw similarities in the strategy employed by the parasite for persistence in different vertebrate classes. Next, the question of host specificity is raised and recent evidence on the subject is examined with an eye toward understanding the distribution of trypanosome species in host communities.

Journal Article↗
PubMedDate not supplied

Review of cefotaxime sodium for surgical prophylaxis. A model for the evolution toward single-dose or short-course cost-effective regimens.

Cefotaxime is a parenteral broad-spectrum cephalosporin, used extensively worldwide for chemotherapy of serious infections. Since its release in 1979, cefotaxime has also been studied to minimize surgery-related infections and, more than any other new compound, has been used in a volume of evaluable cases. Because of the current cost-containment medical practice environment, most cefotaxime prophylaxis studies have established single-dose or short-course regimens. Over 9000 published cefotaxime prophylaxis cases were reviewed, and 81 references were cited. Single-dose cefotaxime was clearly indicated for a wide variety of operations, including hysterectomy, cesarean sections, bone and joint procedures, upper gastrointestinal cases, biliary tract procedures, transurethral resections, open urologic procedures, and some vascular cases. Approximately 24 hr of prophylaxis (cefotaxime X 4 doses) may be required for colorectal resections, cardiac surgery, head and neck surgery, transplants, and some pediatric surgical cases. Although contaminated abdominal cases and trauma surgery were not a true prophylaxis use, cefotaxime regimens have reduced wound morbidity to less than or equal to 10%. Changing to one- to four-dose schedules will have very favorable clinical impact by reducing prophylaxis cost, pharmacy preparation time, adverse reactions, and antimicrobic-resistance pressures. Surgeons should not hesitate to employ new cephalosporins (cefotaxime and others) with proved limited dose indications that would greatly benefit their patients and the hospital environment.

Bacterial Infections↗