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PubMed1996

Antibiotic activity of polyketide products derived from combinatorial biosynthesis: implications for directed evolution.

A library of over 100 polyketides, generated via combinatorial cloning of genes encoding subunits of aromatic polyketide synthases, was screened for molecules capable of inhibiting the growth of gram-positive bacteria. A total of 26 polyketides, with varying levels of antibiotic activity in filter-disk assays, were purified. Most bioactive polyketides were produced as relatively minor compounds (< 1 mg/l), although two major anthraquinones, with yields in the range of 10-100 mg/l, were also identified and structurally characterized. When tested against Bacillus subtilis 168 beta, they were found to cause a 50% reduction in colony-forming units at concentrations of 20 and 300 micrograms/ml, respectively. We speculate that many of the minor (and possibly more potent) bioactive polyketides are synthesized via nonspecific enzymatic modifications of shunt products derived from engineered polyketide synthase pathways. If so, then these 'fortuitous' pathways should be amenable to further rationally guided manipulation. Our results support the notion that combinatorial biosynthesis can be used to generate novel, biologically active molecules. They also point to the feasibility of designing mutagenesis selection experiments aimed at the directed evolution of organic molecules with desirable pharmaceutical properties.

Anti-Bacterial Agents↗

PubMed1997

Coevolutionary chase on exploiter-victim systems with polygenic characters.

I study the dynamics of a simple quantitative genetic model describing coevolution of two antagonistic species of the victim-exploiter type. In this model, individuals are different with respect to an additive polygenic character that is under direct stabilizing selection and which also determines the strength of within and between species interactions. The model assumes that between species interactions are most intense when the victim's and exploiter's phenotypes match. I show that a cyclic coevolutionary chase is possible under a broad range of conditions. In most cases, the system cycles if the "victim" has a stronger incentive to win and/or a larger genetic variance, and is under stronger stabilizing selection than the "exploiter". The results presented here provide counter-examples to recent studies that (1) question the applicability of "Red Queen" and "arms race" metaphors for continuously varying traits; (2) argue for the existence of crucial differences between major and minor loci dynamics; and (3) attribute a stabilizing role to coevolution.

Animals↗

PubMed2002

The major yolk proteins of higher Diptera are homologs of a class of minor yolk proteins in lepidoptera.

In most oviparous animals, including insects, vitellogenin (Vg) is the major yolk protein precursor. However, in the higher Diptera (cyclorrhaphan flies), a class of proteins homologous to lipoprotein lipases called yolk polypeptides (YP) are accumulated by oocytes instead of Vg, which is not produced at all. Lepidopterans (moths) produce Vg as the major yolk protein precursor, but also manufacture a class of minor yolk proteins referred to as egg-specific proteins (ESP) or YP2s. Although the lepidopteran ESP/YP2s are related to lipoprotein lipases, previous attempts to directly demonstrate their homology with higher-dipteran YPs were unsuccessful. In this paper, a multiple alignment of amino acid sequences was constructed using a shared lipid binding motif as an anchor, to demonstrate that lepidopteran ESP/YP2s, higher-dipteran YPs, and lipoprotein lipases are indeed homologous. Phylogenetic analyses of the aligned sequences were performed using both distance-based and parsimony strategies. It is apparent that the higher dipterans did not requisition a lipoprotein lipase to replace Vg as a yolk protein precursor, but instead utilize a class of proteins with an evolutionary history of use as minor constituents of yolk in other insects.

Amino Acid Sequence↗

PubMed1976

Mouse haemoglobin Beta chains. Sequence data on embryonic y chain and genetic linkage of the Y-chain locus to the adult beta-chain locus Hbb.

Embryonic haemoglobin y-chain types were determined by starch-gel electrophoresis for inbred Mus musculus strains Sec/ReJ and Au/SsJ (with Hbbs and Hbbp adult beta-chain alleles respectively) and for random-bred HA/ICR (Swiss) mice, which had been selected to be homozygous for the adult Hbbd beta-chain allele. The strain with the Hbbs allele had y1 embryonic beta chain and the strain with the Hbbd allele had y2. The strain with the Hbbp allele also had y2 chain. A breeding study showed that the maximum recombination frequency between the Hbb locus and the y-chain locus is 5.4% at the 95% confidence level. Embryonic y2 chain was sequenced for 39 positions from the N-terminus with an Edman-Begg sequenator. Some tryptic-peptide composition data were obtained on both y1 and y2 chains. No amino acid substitutions between y1 and y2 chains were found in the 40 positions for which there are common data on the two chains. y2 and adult beta chains are different in 12 of the first 21 positions, but show considerable similarity thereafter. It is suggested that homologous but unequal crossing-over between y-chain and adult beta-chain loci could have given rise to the adult beta-chain allele Hbbd, which produces structurally different major and minor beta chains from two closely linked genes.

Alleles↗

PubMedDate not supplied

[Long-term study of the evolution of chronic bronchitis detected by questionnaire 10 years earlier].

The longitudinal study carried out in a group of inhabitants from Craiova showed that 16,2% of these, classified according to previously filled questionnaires as suffering from chronic bronchitis, and 10,7% of those classified as suffering from minor forms of bronchitis (sporadic symptoms) had died, and one third of them were not found when the investigation was repeated. Re-examination of 106 adults with chronic bronchitis showed that the symptoms had disappeared in two-thirds of them, especially in those who gave up smoking; in 19,8% of them the symptoms had become more severe due to repeated attacks. Bronchial obstruction was present in 36% of the cases, and alterations in the small bronchial ducts were present in two-thirds of the patients. In 18-24% of the patients with minor forms of bronchitis the symptoms were more severe and chronic, and they can be classified as chronically ill patients. Frequently there were altered spirographic values. This study demonstrates that chronic bronchitis may evolve to: a) remission of the symptomatology (especially after suppression of smoking); b) more or less unmodified persistence of symptoms; c) increased severity of the symptoms following repeated acute attacks. Almost 25% of cases with sporadic coughing and expectoration became chronically ill over a period of 10 years. The questionnaire was demonstrated as having retrospective value for making a diagnosis of chronic bronchitis, but cough and expectoration are not sufficient for a differential assessment of the evolution, the spirographic data being of decisive importance.

Bronchitis↗

PubMed1996

The transfer of viable microorganisms between planets.

There is increasing acceptance that catastrophic cosmic impacts have played an important role in shaping the history of terrestrial life. Large asteroid and cometary impacts are also capable of displacing substantial quantities of planetary surface material into space. The discovery of Martian rocks on Earth suggests that viable microorganisms within such ejecta could be exchanged between planets. If this conjecture is correct, it will have profound implications for the origin and evolution of life in the solar system.

Archaea↗

PubMed1996

Chromosomal and molecular divergence in the Indian pygmy field mice Mus booduga-terricolor lineage of the subgenus Mus.

Mus booduga and Mus terricolor both have 2n = 40. Unlike M. booduga, with all acrocentric chromosomes, M. terricolor invariably has large submetacentric X and acrocentric Y due to an increase of heterochromatin. In contrast to the conservative karyotype of the co-existing sibling species booduga, three chromosome types of terricolor are found in different populations and their divergent karyotypes have autosomal heterochromatin variations established in the homozygous condition. The average genetic distance determined from electrophoretic study of 20 protein loci ranges from lowest (D = 0.106) between chromosome types I & II to highest (D = 0.185) between types II & III. In terricolor, booduga and M. m. tytleri high mean values of variations per locus (range A = 1.604 to 1.928) and heterozygosity per individual per locus (range H = 0.180 to 0.336) have been observed. Sequence divergence of 0.39 to 1.2%, calculated from restriction profiles of mtDNA, shows that the terricolor chromosome types have diverged recently. Hybridizations between type I females and type III males gave a preponderance of males in the F1 with varying degrees of sterility. The 'terricolor complex' is an interesting system for critical probing for the role of heterochromatin in the process of speciation. MtDNA, protein loci and AT-rich musculus-related major and minor satellite DNA data indicate that progenitors of the booduga-terricolor lineage might have evolved simultaneously with the caroli-cookii-cervicolor lineage in the evolution of the subgenus Mus.

Animals↗

PubMed1995

Follow-up patency of side branches covered by intracoronary Palmaz-Schatz stent.

To assess the risk of late side branch occlusion after Palmaz-Schatz stent deployment, we analyzed the angiographic evolution of 62 patients treated by successful stent implantation who had a total of 85 side branches starting from the stented segment. Side branches were considered minor (n = 39) when the diameter was < 1 mm and intermediate (n = 46) when the vessel had > or = 1 mm diameter. One angiographic follow-up study was available in all patients at 8 +/- 5 months. Eight minor branches presented some degree of stenosis at origin before stent deployment (4 totally occluded). After stent deployment, 32 (82%) of 39 remained unchanged and 3 became occluded. Late progression at origin occurred in 4 of 34 (3 occluded). Before stent deployment, 48% of the intermediate branches had some compromise degree at their starting point (1 totally occluded). Eight of 45 intermediate branches became occluded after stent implantation. Late progression at origin happened in 5 of 32 branches (2 occluded). Some degree of follow-up stenosis regression at the origin was observed in 22 (26%) of 85 arteries. Neither clinical nor angiographic factors could be identified as predictors of late side branch occlusion or stenosis progression at its origin. Later occlusion or progression at origin of a side branch covered by a Palmaz-Schatz stent seems to be an uncommon occurrence (7% and 12% respectively) that cannot be predicted by angiographic or clinical factors. On the contrary, regression at follow-up of a side branch-origin stenosis can also come about.

Adult↗

PubMed1995

[Hyperexplexia].

Hyperexplexia is a disease of neonatal onset characterized by an exaggerated startle reflex. Early diagnosis is important to rule out epilepsy. Clinical findings are mainly hypertony and generalized startle reflex which is exaggerated by tiredness and some exogenous stimuli. Electroencephalogram is normal. The expression of the disease is variable including minor forms that may be unnoticed and major forms with arthrogryposis-like symptoms, orthopedic complications, false passages, apnea and even sudden infant death (SID). The evolution is generally benign and symptoms disappear within 2 or 3 years. A neuromotor retardation is often present, without intellectual deficit. In severe forms, the risk of SID requires a multidisciplinary follow-up including monitoring and treatment with clonazepam. A low GABA level in cerebrospinal fluid has been reported. Present etiological hypotheses include neuromediator and/or receptor dysfunction.

Humans↗

PubMed1997

Cystic pyeloureteritis: review of 34 cases. Radiologic aspects and differential diagnosis.

OBJECTIVES: To refine the clinical and radiologic description of an unusual benign disease, cystic pyeloureteritis (CPU), consisting of the appearance of suburothelial cysts that raise the mucosa layer of the urothelium. We also studied its relationship with various types of inflammation, including chronic infection, that may be the stimulus for the appearance of CPU. METHODS: We compiled 34 cases of CPU covering the period 1976 to 1994, analyzing the clinical manifestations, diagnostic procedures, differential diagnosis, and evolution. RESULTS: There are no specific symptoms associated with the presence of cysts. The average age of the patients was 59 years (range 30 to 77). Urinary tract infection was detected in 18 (53%). The pyeloureteritis was unilateral in 27 (79%) and bilateral in 7 (21%) of the patients. The location of the cysts was as follows: 1 pyelic (3%); 6 pyeloureteral (18%); and 27 (79%) ureteral. Resolution of the radiologic alterations depends on the resolution of the associated pathology: infections, lithiasis, and obstruction. CONCLUSIONS: We conclude that CPU is a benign pathology with indolent evolution and variable duration; it is not associated with sequelae. Diagnosis is made on the basis of radiologic findings, mainly intravenous urography; in view of the minor entity of the pathology, biopsy is not advisable if the radiologic findings are conclusive.

Adult↗

PubMedDate not supplied

[The prognostic value of the E.E.G. in premature infants (author's transl)].

The electroencephalograms of 82 infants (between 27 and 37 weeks of conceptional age) recorded during the neonatal period were analyzed and compared with the ultimate clinical evolution. Three groups of infants were identified according to their neurological state at 3 years of age or older: group A: normal (34 infants), group B: minor neurological sequellae (13 infants) and group C: major neurological sequellae (17 infants). A fourth group (group D: 18 infants) died during the neonatal period. The E.E.Gs were classified as: normal, questionably abnormal, moderately abnormal or grossly abnormal. The analysis revealed that E.E.Gs classified as grossly abnormal, were found only in groups B, C and D. Serial E.E.Gs were of more value in distinguishing these groups. Only infants in groups C and D (with I exceptional case in group B) had E.E.Gs which remained abnormal for several weeks or which deteriorated during the neonatal period. This study shows the prognostic value of the E.E.G. recorded during the neonatal period, particularly serial recordings obtained during and after a period of clinical deterioration. A detailed statistical analysis of the E.E.Gs is in progress.

Aging↗

PubMed2000

Penicillin binding proteins, beta-lactams, and lactamases: offensives, attacks, and defensive countermeasures.

A strong outer covering of peptidoglycan (the sacculus) is essential for most bacteria. Beta-lactams have evolved billions of years ago and can block saccular growth of the organism. This led to the evolution of beta-lactamases and resistant penicillin binding proteins (PBPs). With the introduction of lactam antibiotics by the pharmaceutical industry, resistance genes in nature were laterally transferred to antibiotic-treated disease-causing organisms and additional modification of beta-lactamase genes and of the regulatory genes of the mecA region took place. However, it can be concluded that very little of either type of resistance mechanisms represents new basic evolution against the penicillin type antibiotics. In the last 60 years the resistant bacteria in the main arose by movement of genes from other organisms, from minor genetic changes, and from alteration of the regulation of synthesis.

Bacteria↗

PubMed2003

Genome-wide analysis of Bkm sequences (GATA repeats): predominant association with sex chromosomes and potential role in higher order chromatin organization and function.

MOTIVATION: Bkm (Banded krait minor) satellite DNA sequences (GATA repeats) have been shown to be associated with the sex determining chromosomes of various eukaryotes and have been implicated in the evolution and differentiation of sex chromosomes in snakes. The objective of the study is to analyze the GATA repeats of human genome specifically, the Y-chromosome, and other model organisms to understand the possible function and potential role in higher order chromatin organization. RESULTS: Our extensive analysis of GATA repeats in the prokaryotic and eukaryotic genomes, which have been completely sequenced so far, has revealed that GATA repeats are absent in prokaryotes and have been gradually accumulated in higher organisms during the course of evolution. In human, the Y-chromosome has the highest GATA repeat density, which predominantly exists in the Yq centromeric region. Generally, occurrence of repeats in the genomes decreases steadily as the length of the repeat increases. In contrast, we report, that the occurrence of GATA repeats increases as the length of the repeat increases from six tandem repeats onwards and peaks at (GATA)(10-12). This has not been observed with any other simple repeat. Distribution of (GATA)(10-12) along the chromosome and their close proximity to Matrix Associated Regions (GATA-MAR) suggests that it may be demarking chromatin domains for a coordinated expression of genes residing in these domains.

Animals↗

PubMed1975

Methods of evaluating the sequestration site of red cells labelled with 51Cr: a review of 96 cases.

Teh technical conditions for surface counting and the methods for splenic and liver sequestration after injection of 51Cr-labelled cells were studied in 96 patients. A comparative study of different sites of positioning of the detection probes leads us to recommend the mid-line at the third intercostal space for the precordial area, the point of maximum count-rate obtained at each measurement for the splenic area, with the patient in right lateral decubitus position and the probe vertical, and a point situated on the midclavicular line 4 cm above the right costal margin for the liver area. A comparative study of different methods of calculation leads us to recommend the method known as 'excess counts', but with a correction of the gross values based on the evolution of circulating radioactivity and not of the count-rate measured over the precordial area. Measurement of urinary excretion of radioactivity showed that only a minor part was due to the loss of the tracer from the sequestration sites, and that the level varied only slightly between subjects. Thus the loss of tracer does not interfere with the interpretation of external counting data. Much of the disagreement regarding interpretation of the results of external counting in clinical practice is due to technical problems. Standardization of techniques of measurement and interpretation of results, selecting those which this study indicates as the most reliable, would permit better exchange of information between laboratories and clearer conclusions as to the practical use of surface counting.

Chromium Radioisotopes↗

PubMed1990

Immunocytogenetics. IV. Human autoantibodies to heterochromatin-associated proteins.

We report here a novel class of human autoantibodies with immunological affinity for constitutive heterochromatin. Indirect immunofluorescence localized different proteinaceous antigens to the AT-rich paracentromeric heterochromatin of mouse chromosomes, the GC-rich heterochromatic regions of sheep chromosomes, and the large C-banded regions of human chromosomes 1, 9, and 16. Minor amounts of the heterochromatin-associated proteins were uniformly distributed on the chromosomes of all vertebrate species. Their antigenic determinants have been highly conserved during evolution. The chromosomal distribution of the heterochromatin-associated antigens is not altered in interspecific somatic cell hybrids but apparently reflects a stable structural property germane to each chromosome type. The antigenic proteins remain bound to their respective epitopes throughout the entire cell cycle and in meiosis. The heterochromatin-associated antigens represent a major nonhistone component of the mitotic chromosome scaffold and the interphase nuclear matrix. Immunoblotting performed with a human autoimmune serum to mouse heterochromatin revealed a characteristic pattern of polypeptides with molecular weights ranging from 35 to 120 kDal. Drugs that interfere in vivo with the higher-order chromatin structure had no effect on the expression and chromosomal distribution of the heterochromatin-associated antigens. However, the antibody binding sites in chromatin can be completely masked by treating fixed cell preparations with certain DNA-binding ligands.

Animals↗

PubMed1981

The use of brain electrical potentials (BEP) to study localization of human brain function.

Various techniques such as neuropsychological diagnosis of individuals with focal lesions, stimulation of neurosurgery patients, and regional cerebral blood flow have been used to elucidate the major anatomical and functional divisions of the human cerebral cortex. Because of insufficient spatial sampling and other limitations, only minor support for these divisions comes from brain electrical potential (BEP) experimentation. The use of EEG to localize different neuropathologies and to screen and track the evolution of seizure disorders is fairly reliable and still widely practiced. Its use, however, in localizing higher cognitive functions is much more complicated and has not stood the test of scientific scrutiny because of methodological problems. More specifically, the failure to control for the stimulus, response and performance related properties of tasks in experiments has rendered ambiguous the results of most EEG studies of higher cognitive functions. Those studies which actually controlled for these properties did not find and differences between tasks.

Brain↗

PubMedDate not supplied

[Cerebral dissecting aneurysms].

INTRODUCTION: Blood stream penetrates through the lacerations of the arterial layers determining dissecting aneurysms. Each intramural clot localization determines different clinical form. OBJECTIVE: We present the clinical observations carried out in two patients with vertebrobasilar dissecting aneurysms and we review the state of the art of this process to remark the early identification of these unusual lesions. CASE REPORTS: Two cases of vertebrobasilar dissecting aneurysms were described. They were young patients that debuted, one as posteroinferior artery brain steam infarction and the other one as a subarachnoid hemorrhage caused by a right posterior cerebral artery dissecting aneurysms. Lesions were confirmed by helicoidal cerebral angiotomographic and angiograms. This patient was operated on and we clipped the posterior communicating that irrigated dissecting segment. We carry out an anatomical and hemodynamic analysis of that lesion. Both patients had a satisfactory clinical evolution. CONCLUSIONS: Dissecting intramural hematomas of the vertebrobasilar territory are frequent cause of young people ictus. It has been suggested that the ictus may happen after minor head trauma and pain, main symptom, always precedes neurological dysfunction signs. Hemorrhagic presentation has a high incidence of rebleeding and elevated mortality. It always requires, as soon as possible, direct microsurgical treatment or endovascular methods (coils). Most useful microsurgical procedure, until today, is parent artery clipping. This technique has a low index of isquemic and neural postoperative damage.

Adult↗

PubMed1977

[Cerebral arterial embolism during extracorporeal circulation].

From October 1st 1970 to October 1st 1975, electrical and clinical post-operative observation of 1.700 operations under E.C.C. allowed record of E.E.G. and thus study incidents depending of cerebral embolism during their formation. 18 cases have been seen during E.C.C. and 2 at the stop of E.C.C. In 9 cases, it was an air embolus, in 4 others an atheromatous embolus. In the 7 remaining cases, origin of the embolus is uncertain, but probably gaseous. Semiology of the accident is first only E.E.G. In 10 cases, signs were minor, and moderate in 10 others, preceding a late but hard clinical symptomatology, frequently characterized by a delayed advent of epilepsy crisis. Later on, an annoying evolution of the accident was seen in 4 cases (1 death, 3 lasting neurologic deficiency). For the treatment, many observations confirm the highly beneficient part of early hyperbaric oxygen.

Adolescent↗