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[An ELISA test for the study of the therapeutic evolution of chromoblastomycosis by Cladophialophora carrionii in the endemic area of Falcon State, Venezuela].

The purpose of this research was to evaluate an ELISA indirect method in patients with chromoblastomycosis caused by Cladophialophora carrionii. Samples collected before, during and postreatment with ajoene or itraconazole, and those from apparently healthy people from the endemic area were evaluated with the ELISA test. 94 individuals were studied, 10 with chromoblastomycosis, and 84 apparently healthy subjects. All of them were evaluated by clinical-dermatological examinations. On those with lesions suggestive of chromoblastomycosis, mycological studies were carried out to confirm the disease. This approach was repeated during and at the end of therapy. Five patients with lesions < or = 5 cms were treated with ajoene and five with lesions > 5 cms, received itraconazole. Mycological cure (60%) was similar in both groups of patients and persisted three months after therapy. One hundred and fourteen sera were analyzed by ELISA, 30 from 10 patients with chromoblastomycosis, before, during and postreatment and 84 from apparently healthy people, using a somatic antigen of C. carrionii (AgSPP). All patients with chromoblastomycosis were positive before-treatment, two became negative on day 45 of treatment and a total of six patients were negative three months post-treatment. All sera from apparently healthy individuals were negative. The sensitivity and specificity was 100% and 98.9%, respectively. The relationship between clinical-mycological studies and the ELISA assay was 100% before and after treatment. In summary, ELISA could be a valuable tool for the diagnosis and evolution of the therapeutic efficacy in patients with chromomycosis (C. carrionii). The use of an ELISA test is therefore highly recommended to establish remission criteria in chromoblastomycosis caused by C. carrionii.

Adolescent↗

The evolution of an immune system.

A model for the molecular evolution of an imune system is presented. It suggests how a system of cell surface-fixed antigen receptors, called FR, to be thought of as "primitive" but still functional antibodies, could evolve into the "modern" labile T cell and antibody system, the receptors for which may be called CER (clonal expansion receptors). Perhaps the most significant insight to be gained from the theory concerns the conclusion that the immune system of an embryo may be primed by the interaction between two types of cells with complementary surface specificities. In the first type of cell the interacting molecule is an FR molecule coded by a gene of the Major Histocompatibility Complex (MHC) which has undergone a somatic mutation; in the second type it is a CER molecule also coded by a gene which has undergone a recent somatic mutation. It is believed that this insight eliminates some of the problems experienced in understanding generation of diversity, and renders unnecessary some of the more complex hypotheses about immune networks. The mechanism of action of immune response genes is easily explained by the theory.

Adaptation, Physiological↗

Solar cycles and their relationship to human disease and adaptability.

In this paper, we show that 11-year solar cycle peaks predispose humans to disease, but also endow creativity and adaptability. We give several examples of diseases that are modulated by light and present evidence for an effect of intensity and variation in sunlight, primarily ultraviolet radiation (UVR), on the human genome. The birth dates of nearly 237,000 unique clients in the Maine Medicaid database collected from 1995 to 2004, inclusive, were related to solar cycle irradiance for the past seventy-one years, encompassing seven solar cycles. The sample was divided into four general categories of disease: mental/behavioral illnesses; metabolic diseases; autoimmune diseases; neoplasms. The birth months for those clients born in any given year were arranged in the form of a winter/summer ratio in order to more clearly appreciate the seasonality inherent in each disease category. Solar cycles were separated into chaotic (approximately three times as irradiant) or non-chaotic according to the Gutenberg-Richter power law and the uncertainty inherent in predicting solar storms. The results show that radiation peaks in solar cycles and particularly in chaotic solar cycles (CSCs) are associated with a higher incidence of mental disorders, suggesting the sensitivity of ectodermal embryonic tissues to UVR. Autoimmune diseases have intermediate sensitivity, while the neoplasms in the study, primarily of endoderm, appear suppressed by peak UVR intensity. The ratio of the number of clients born in CSC cycles to non-CSC cycles was highest for the more genetic mental diseases, like schizophrenia and bipolar disorder, but as that ratio decreased, the clients with diseases like multiple sclerosis and rheumatoid arthritis showed more environmental features manifested as a greater winter/summer birth month ratio that was significantly different than that of the average client in the whole data set. The paper presents evidence that latitude, e.g., variation in light, is an added stress to the immune system (especially at 53-54 degrees N. latitude) that is involved in nearly all human disease. We hypothesize that introns, the presumptive engenderers of gene control, modulate the effects of UVR, particularly for the neoplasms studied. We conclude that intermittent and largely unpredictable peak solar cycle radiation has been the fundamental engine of evolution, forcing organisms to adapt to mutagenic UVR and producing enough damage to instigate genetic variation. Probably a chance genetic mutation over 80,000 years ago produced a human brain capable of abstract thought and consciousness. The slight genetic instability that favored an adaptable, creative brain also produced other somatic variations that present phenotypically as disease, but largely expressed after natural selection (reproduction) and associated with the inexorable entropy of aging.

Adaptation, Physiological↗

The Drosophila melanogaster RAD54 homolog, DmRAD54, is involved in the repair of radiation damage and recombination.

The RAD54 gene of Saccharomyces cerevisiae plays a crucial role in recombinational repair of double-strand breaks in DNA. Here the isolation and functional characterization of the RAD54 homolog of the fruit fly Drosophila melanogaster, DmRAD54, are described. The putative Dmrad54 protein displays 46 to 57% identity to its homologs from yeast and mammals. DmRAD54 RNA was detected at all stages of fly development, but an increased level was observed in early embryos and ovarian tissue. To determine the function of DmRAD54, a null mutant was isolated by random mutagenesis. DmRADS4-deficient flies develop normally, but the females are sterile. Early development appears normal, but the eggs do not hatch, indicating an essential role for DmRAD54 in development. The larvae of mutant flies are highly sensitive to X rays and methyl methanesulfonate. Moreover, this mutant is defective in X-ray-induced mitotic recombination as measured by a somatic mutation and recombination test. These phenotypes are consistent with a defect in the repair of double-strand breaks and imply that the RAD54 gene is crucial in repair and recombination in a multicellular organism. The results also indicate that the recombinational repair pathway is functionally conserved in evolution.

Amino Acid Sequence↗

[Transmission and expression of malignancy in somatic hybrid cell lines (hamster/hamster, mouse/mouse, hamster/mouse)].

Various characteristics of transformation were studied in subclones isolated from a hybrid cell line obtained by fusion of two Chinese hamster sub-lines having the same origin but presenting different properties, particularly in respect to heterotransplantability. Different subclones were obtained by cloning on semisoft agar. Transplantability, plating efficiency, agglutinability by concanavalin A and actinomycin D resistance were studied in parallel with the evolution of the karyotype to try to find a correlation between these various parameters. A relationship seems to exist between a chromosome marker arising in the hybrid and the percentage of tumours. The second part of this work dealth with the study of intra and interspecies hybrids, one of the parents of which was a normal, fibroblastic cell and the other of which contained the polyoma virus genome. In the hybrid cell this viral genome was expressed at several levels. Firstly, in the formation of specific polyoma virus-induced antigens and secondaryly, in surface properties normally considered related to the expression of tumorigenicity. Nevertheless, tumour development was repressed. Though the presence of characteristic antigens seemed necessary for the expression of malignant transformation, presence alone was not sufficient to induce malignant transformation of the cell. The study of inter-species mouse/hamster hybrids showed that this situation is not general. For this we examined the properties of hybrid cells between, on the one hand, a mouse tumorigenic cell bearing polyoma virus genetic information and, on the other, non-tumorigenic mouse or hamster cell. In this case the complete hamster genome could bot repress malignancy whereas a few mouse chromosomes sufficed to code for the expression of virus-induced tumour antigens and various malignant properties. It may be hoped that these hybrids could be used to pin-point the chromosome localization of the genetic factors of malignancy and could be used in immunoprotection studies or immunotherapy research.

Agglutination↗

[The evolution of the forms of hermaphroditism in Cyclophyllidea (Cestoda). 2. Morphofunctional causes of the formation of tapeworms having a protogynous type of the genital apparatus development].

Morpho-biological causes of the formation of protogynous forms of Anoplocephalidae (Cyclophyllidea) parasitizing rodents have been studied. The reduction in the number of segments in the strobila of anoplocephalideans (Anoplocephaloides, Paranoplocephaloides) in comparison with related polymeric species of the taxon (Paranoplocephala) suggests that protogyny is resulted from the secondary oligomerization of strobila in the phylogenesis of these cestodes. It is evident that the ecological cause of the selection for a small number of segments in the strobila is a tough competition among large polymeric cestodes that results in the formation of small anoplocephalideans located in the back part of the small intestine (Paranoplocephaloides) and in the blind gut (Anoplocephaloides) of rodents. There is slowing down of strobilation rates, acceleration of genital apparatus development and somatic proglottid morphogenesis during the change into protogyny. Due to an earlier, regarding testicle morphogenesis, formation of the ovary and uterus, uterus segments are developing most of the time in the strobila. Thus, proterogyny is one of the universal mechanisms to extend the terms of hexacanth embryogenesis in the second oligomeric strobila of tapeworms.

Adaptation, Physiological↗

No sex please, we're mitochondria: a hypothesis on the somatic unit of inheritance of mammalian mtDNA.

In this article we develop a model for the organization and maintenance of mitochondrial DNA (mtDNA) in mammalian somatic cells, based on the idea that the unit of genetic function comprises a group of mtDNA molecules that are semi-permanently associated as a mitochondrial nucleoid. Different mtDNA molecules within a nucleoid need not be genetically identical. We propose that nucleoids replicate faithfully via a kind of mitochondrial mitosis, generating daughter nucleoids that are identical copies of each other, but which can themselves segregate freely. This model can account for the very slow rates of mitotic segregation observed in cultured, heteroplasmic cell-lines, and also for the apparently poor complementation observed between different mutant mtDNAs co-introduced into rho(0) cells (cells that lack endogenous mtDNA). It also provides a potential system for maintaining the mitochondrial genetic fitness of stem cells in the face of a presumed high somatic mutation rate of mtDNA and many rounds of cell division in the absence of phenotypic selection. BioEssays 22:564-572, 2000.

Animals↗

Evolutionary advantages of cell specialization: save and protect DNA.

As the transcribed regions of nuclear DNA are in a more open state, they are liable to be damaged by naturally or environmentally produced mutagens. Cell specializations make it possible to express fewer genes in individual cells of multicellular organisms, thus protecting genes from the damage of mutagens. We propose that this might account for the advantage of cell specialization, as an alternative to the traditional conception that cell specializations result in increased efficiency. The most efficient cell specialization to protect DNA is in the segregation of germ cell(s) and somatic cell(s). But in optimal environments, such specialization is expected to reduce the rate of reproduction, which might counteract its advantage of protecting DNA.

Animals↗

The development of sensorimotor reflexes in the Brazilian opossum Monodelphis domestica.

The development of a number of sensorimotor reflexes was studied in the Brazilian opossum Monodelphis domestica. At birth, an opossum's forelimbs execute rhythmic, alternate movements which resemble swimming, whereas the hindlimbs are little more than embryonic buds that do not move independent of the trunk. It is possible, therefore, to witness the entire development of hindlimb motility, the advent of coordination between forelimbs and hindlimbs, and the development of ambulation. The following sequence in the appearance and maturation of the reflexes was observed: rooting, an innate reflex in mammals which disappears over time; withdrawal of the forelimbs followed by withdrawal of the hindlimbs; crossed extension of the forelimbs and then of the hindlimbs; grasp, the forelimbs preceding the hindlimbs; body righting on a surface; forward hopping of the forelimbs followed by the hindlimbs; lateral and medial hopping of the forelimbs, then the hindlimbs; chin tactile placing; body righting in the air; and, finally, visual placing. Limb tactile placing is not significantly expressed, even in the adult. This behavioral sequence generally matches the sequence of somatic (trunk, limbs, head) and neural (spinal cord and brain) structures involved in the control of these behaviors.

Age Factors↗

An epigenetic mutation responsible for natural variation in floral symmetry.

Although there have been many molecular studies of morphological mutants generated in the laboratory, it is unclear how these are related to mutants in natural populations, where the constraints of natural selection and breeding structure are quite different. Here we characterize a naturally occurring mutant of Linaria vulgaris, originally described more than 250 years ago by Linnaeus, in which the fundamental symmetry of the flower is changed from bilateral to radial. We show that the mutant carries a defect in Lcyc, a homologue of the cycloidea gene which controls dorsoventral asymmetry in Antirrhinum. The Lcyc gene is extensively methylated and transcriptionally silent in the mutant. This modification is heritable and co-segregates with the mutant phenotype. Occasionally the mutant reverts phenotypically during somatic development, correlating with demethylation of Lcyc and restoration of gene expression. It is surprising that the first natural morphological mutant to be characterized should trace to methylation, given the rarity of this mutational mechanism in the laboratory. This indicates that epigenetic mutations may play a more significant role in evolution than has hitherto been suspected.

Amino Acid Sequence↗

A morphological study of the cochlear nuclei of the pigeon (Columba livia).

The pigeon cochlear nucleus angularis (NA) and nucleus magnocellularis (NM) were analyzed with Golgi and Nissl techniques. NA was divided into a medial NAm and NA proper, which could be subdivided further into an intermediate NAi and lateral NAl. NAm contained a mostly homogeneous population of a unique multipolar cell type with very short dendrites and large somatic spines. NA proper contained four cell types: large, medium, and small multipolars, and medium bipolar. The medium multipolar cells were most common, and resembled the multipolar cells of the mammalian ventral cochlear nucleus. NM presented a homogenous appearance with a mediolateral gradient of cell size and shape. Medially located higher best frequency NM principal cells had round cell bodies with small somatic spines and few dendrites. By comparison, laterally located low best frequency NM stellate cells had more dendrites and spindle shaped cell bodies. The similarities between the cell types of NA and the cell types in the cochlear nuclei of other amniote vertebrates may be due to homology or convergent evolution.

Animals↗

[The biological aspects of chromatin diminution].

The chromatine diminution (CD), first discovered by Boveri (1887) in ascarids, represents programmed elimination of a part of genetic material in the nuclei of the somatic cells in cyclops and ascarids, and in the protist macronuclei. The CD can be considered as a macromutation sharply changing chromosomal structure, though minimally effecting the phenotype. The analysis of CD is of significance for discussing mechanisms of origin of chromosomal organization, transformation of genome molecular structure in eucaryote evolution, role of the extra DNA.

Animals↗

Meiosis-specific transcripts of a DNA component replicated during chromosome pairing: homology across the phylogenetic spectrum.

In meiotic cells of Lilium, a group of single or low copy number DNA sequences that constitute about 0.1-0.2% of the genome do not replicate during the premeiotic S-phase but do so at zygotene in coordination with chromosome pairing. An appreciable fraction of these sequences has now been found to be transcribed into poly(A)+ RNA when chromosomes initiate the pairing process. This "zygRNA" has not been detected in nonmeiotic tissues. Even within the meiocytes, zygRNA is not detectable prior to leptotene or beyond midpachytene. S1 nuclease digestion of mouse spermatocyte nuclei selectively released zygDNA, which hybridizes with lily zygRNA. zygRNA has not been detected in mouse somatic tissues. The profile of zygRNA formation and disappearance in mouse spermatocytes is very similar to that of zygRNA in lily meiocytes.

Animals↗

Regional mapping of short tandem repeats on human chromosome 10: cytochrome P450 gene CYP2E, D10S196, D10S220, and D10S225.

Human CYP2E encodes an ethanol-inducible cytochrome P450 monooxygenase that metabolizes various carcinogens and may therefore play a role in cancer susceptibility. An intronic (GGAT)n.(CCTA)n repeat element was found to display limited polymorphism in Caucasoids and was used as a sequence-tagged site for genomic amplification from somatic cell hybrids to localize CYP2E to 10q24.3-qter; using the same panel, three microsatellite markers, D10S196, D10S220, and D10S225, were mapped to 10q21. The close synteny of CYP2E, CYP2C, and CYP17 belonging to two different cytochrome P450 families suggests a central role for the long arm of chromosome 10 in the evolution of this large gene superfamily.

Adult↗

Analysis of patterns of DNA sequence variation in flanking and coding regions of murine germ-line immunoglobulin heavy-chain variable genes: evolutionary implications.

We analyzed the DNA sequence structure of the 5' flanking and coding regions of 52 VH186.2-related germ-line genes isolated by PCR from C57BL/6J and BALB/c mice. The aligned coding regions display hypervariable and conserved regions corresponding to some of the complementarity-determining regions (CDRs) and framework regions (FRs) found in somatically mutated rearranged immunoglobulin variable genes. Most of the coding regions (88.5%) display open reading frames, strongly suggesting positive selection by antigen. Phylogenetic comparisons of putative transcribed regions versus 5' nontranscribed regions show that they have evolved very differently. Inspection of the 52 murine VH186.2-related DNA sequences (as well as other vertebrate germ-line V sequences reported in the literature) reveals clusters of insertion and deletion events bracketing the transcription/coding unit. These data strongly suggest hyperrecombination events targeting the putative transcription/coding sequence. Given that the DNA of unrearranged germ-line V elements cannot be the direct target for "natural-selection" antigen-binding forces (since V elements are only expressed somatically when rearranged in a mature lymphocyte), it is difficult to explain how these nonrandom sequence variations appear in the germ-line DNA. A number of molecular genetic processes are considered, including antigen-driven soma-to-germ-line gene feedback operative during vertebrate germ-line V gene evolution.

Amino Acid Sequence↗

Energy metabolism, brain size and longevity in mammals.

The mathematical relations between basal energy metabolism, brain size, and life span in mammals have been investigated. The evolutionary level of brain development, or encephalization (c), is a function both of brain weight (E) and of body weight (P) according to (formula; see text) Brain weight was found to be a linear function of the product of encephalization and basal metabolic rate. The oxygen consumption of the brain (Mbrain) is proportional to both encephalization and body weight according to (formula; see text) The ratio of metabolic rate in the cerebral cortex to that in the brain as a whole depends solely upon the degree of encephalization and is independent of the size of the animal. The maximum potential life span of a mammal was found to be proportional to the product of its degree of encephalization and the reciprocal of its metabolic rate per unit weight. Life span may be regarded as the algebraic sum of two components: (1) a deduced somatic component (Lb) inversely related to the basal metabolic rate per unit weight, and (2) an encephalization component (Le) related directly to the evolutionary increase of relative brain size.

Animals↗

Nucleotide sequence of a chromosomal rearranged lambda 2 immunoglobulin gene of mouse.

The rearranged lambda 2 gene of the mouse plasmacytoma cell line MOPC315 has been cloned and sequenced. A comparison of its sequence with the sequence of the unrearranged (germ-line) V, J and C gene segments shows that the sequences of the V gene segments differ at six positions. The sequence of the J and C gene segments remained unchanged. These results add support to the hypothesis that somatic mutations occur in immunoglobulin in genes and that these mutations do not involve the C gene segment. The degree of homology of the elements of the lambda 2 gene with those of the lambda 1 gene and C lambda 3 and C lambda 4 gene fragments suggest a pathway of evolution by gene duplication of the immunoglobulin lambda light chain locus. According to this scheme the original structure V0-J0C0 gave rise to a structure V0-J1C1-J11C11 by duplication of the J0C0 region. A second duplication encompassing the whole region resulted in the present structure: V1-J3C3-J1C1/V2-J2C2-J4C4.

Animals↗