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Male-driven evolution in closely related species of the mouse genus Mus.

Recently, other researchers have found that closely related primate species had a lower male-to-female mutation rate ratio (alpha) than distantly related species. To determine if this is a general phenomenon affecting other mammalian orders, eleven species or subspecies of the rodent genus Mus and two outgroup species were compared. Intron sequences from a gene in the nonrecombining region of the Y chromosome Jarid1d (Smcy) and its X chromosomal gametolog, Jarid1c (Smcx), were analyzed in a phylogenetic context. The male-to-female mutation rate ratio for all thirteen taxa is approximately 2.5, which is similar to previous estimates in more distantly related rodents. However, when branches with lengths of more than 2.5% were removed from the analysis, the male-to-female mutation rate ratio dropped to 0.9. Thus, in closely related rodents, as in closely related primates, the male-to-female mutation rate ratio is lower than expected.

Animals↗

Photosynthetic capacity of leaves of Eucalyptus globulus (Labill.) growing in the field with different nutrient and water supplies.

The effects of water and nutrient availability on photosynthetic capacity of juvenile and adult leaves of Eucalyptus globulus Labill. seedlings were evaluated by measuring oxygen evolution at light and CO(2) saturation. Seedlings supplied with near optimal amounts of water and nutrients had higher growth rates than non-irrigated, unfertilized control seedlings, but photosynthetic capacity was similar in both treatments. Differences in foliar nitrogen concentrations between the two treatments were minor, which largely explains why the growth response to near optimal nutrition was not associated with an increase in photosynthetic capacity per unit leaf area. Nevertheless, the photosynthetic capacity of juvenile leaves decreased from distal to proximal positions in the mid-crown and was positively correlated with leaf nitrogen concentration expressed on a leaf surface area basis. During the dry season, non-irrigated, unfertilized seedlings fixed carbon at lower rates than irrigated seedlings supplied with near optimal nutrition because of stomatal closure even though photosynthetic capacity was unaffected by water deficits. In both treatments, there were differences between the photosynthetic capacity of adult and juvenile leaves that were largely explained by the low specific leaf area of adult leaves.

Journal Article↗

A gene outside the human MHC related to classical HLA class I genes.

By presenting antigenic peptides to T lymphocytes, major histocompatibility complex (MHC) class I molecules play important roles in the human immune system. Knowledge is limited on the evolutionary history of human MHC class I-related molecules. An expressed class I gene, MR1, has now been identified on human chromosome 1q25, outside the MHC. In contrast to other known human divergent class I genes, MR1 encodes peptide-binding domains similar to those encoded by human leukocyte antigen (HLA) class I genes on chromosome 6 and by nonmammalian classical MHC class I genes. This gene may thus contribute to understanding the evolution of the MHC.

Amino Acid Sequence↗

Treatment of adult myelodysplastic syndromes.

Patients with myelodysplastic syndromes (MDS) suffer from pancytopenia and are at substantial risk for progression to acute myeloid leukemia. The principal pathogenetic features of MDS are clonal evolution, ineffective hematopoiesis (apoptosis), and reduced cellular maturation. T-cell-mediated myelosupression may add to disease development in some patients. The disease is progressive and, for the majority of patients, the aim of treatment will be to improve blood values and quality of life. A minority of patients could be cured by allogeneic bone marrow transplantation, which results in an overall disease-free survival of about 40%. The value of autologous stem-cell transplantation is currently being investigated in clinical trials; this treatment may be found to be beneficial for some MDS patients. High-dose chemotherapy may lead to significant improvement and complete remission in about 50% of treated patients, but remission duration is usually short. Low-dose chemotherapy may also be used to improve peripheral blood values. Several new low-dose treatments are being tested at present. Growth factors can be used to improve both ineffective hematopoiesis and cytopenia. The value of treatment with growth factors alone for granulocytopoiesis is uncertain, whereas treatment for impaired erythropoiesis using erythropoietin alone or erythropoietin in combination with other growth factors seems more promising. Subgroups of MDS in which T-cell-mediated myelosuppression are present may respond favorably to cyclosporin A or antithymoglobulin. Antiapoptotic agents such as amifostine may improve blood values in some patients with MDS, but the value of this treatment is not yet clear. Increasing pathogenetic knowledge and better use of predictive models have resulted in some progress in MDS treatment. In the future, more effective treatments may result from further insights into the biology of the disease, the discovery of new therapeutic approaches, and the search for better ways to use existing therapeutic options.

Adult↗

Femoral neck anteversion: values, development, measurement, common problems.

The femoral neck anteversion angle is an important factor for hip stability and normal walking. It is multifactoral result of evolution, heredity, fetal development, intrauterine position, and mechanical forces. Abnormal FNA sometimes can be associated with many clinical problems ranging from harmless intoeing gait in the early childhood, to disabling osteoarthritis of the hip and the knee in the adults. In most cases is associated with minor functional problems in children during growth, but cause a concern in parents for children future. The child must be examined carefully and an accurate diagnosis must be established. The most important part of care is observation of the children. If abnormal femoral neck anteversion produces severe functional disability, derotational osteotomy should be done, but delayed until late childhood.

Adolescent↗

The genus Leishmania.

The systematic position of the so-called "species" of Leishmania is examined and an attempt made to determine their phylogenetic relationships. The morphology of the organisms as seen by light- and electron-microscopy is described; neither method provides useful criteria for the determination of species. The behaviour of the parasites in insect and in vertebrate hosts offers a better method of classification. In this way, the species may be divided into 4 main groups, comprising the mammalian species involving man, the distinctive species L. enriettii in the guinea-pig, those infecting lizards, and species apparently in various stages of evolution in phlebotomines. The so-called "human" group is divided into visceral forms (originating chiefly in wild canidae) and cutaneous forms (probably of rodent origin). The named species of the former group include L. donovani and L. infantum. The cutaneous species include L. tropica tropica (=minor), L. tropica major, L. brasiliensis, L. peruana, L. guyanensis, and L. mexicana. L. pifanoi is probably not a distinct species but represents various forms as modified by the failure of cell-mediated immunity in the host. Leishmanial infections can be identified first by ascertaining the geographical area where the infection was acquired, and then by more or less complicated laboratory investigations including characteristics in culture, serological tests, the response of special hosts in terms of symptomatology, and the behaviour of the parasite in the phlebotomine host. No test is infallible, and an effective simple test is urgently needed. The preservation of Leishmania strains is an important research procedure and a method for conserving parasites by lyophilization is described briefly.

Animals↗

Evolution of mitochondrial gene content: gene loss and transfer to the nucleus.

Mitochondrial gene content is highly variable across extant eukaryotes. The number of mitochondrial protein genes varies from 3 to 67, while tRNA gene content varies from 0 to 27. Moreover, these numbers exclude the many diverse lineages of non-respiring eukaryotes that lack a mitochondrial genome yet still contain a mitochondrion, albeit one often highly derived in ultrastructure and metabolic function, such as the hydrogenosome. Diversity in tRNA gene content primarily reflects differential usage of imported tRNAs of nuclear origin. In the case of protein genes, most of this diversity reflects differential degrees of functional gene transfer to the nucleus, with more minor contributions resulting from gene loss from the cell as a consequence of either substitution via a functional nuclear homolog or the cell's dispensation of the function of the gene product. The tempo and pattern of mitochondrial gene loss is highly episodic, both across the broad sweep of eukaryotes and within such well-studied groups as angiosperms. All animals, some plants, and certain other groups of eukaryotes are mired in profound stases in mitochondrial gene content, whereas other lineages have experienced relatively frequent gene loss. Loss and transfer to the nucleus of ribosomal protein and succinate dehydrogenase genes has been especially frequent, sporadic, and episodic during angiosperm evolution. Potential mechanisms for activation of transferred genes have been inferred, and intermediate stages in the process have been identified by comparative studies. Several hypotheses have been proposed for why mitochondrial genes are transferred to the nucleus, why mitochondria retain genomes, and why functional gene transfer is almost exclusively unidirectional.

Cell Nucleus↗

Readiness for drug use prevention in rural minority communities.

An assessment of community readiness for drug use prevention in rural communities indicated that most rural communities are at relatively low stages of readiness. Minority communities were particularly low in readiness, with only 2% having functioning drug prevention programs. Rural communities at different levels of readiness require different types of programs to increase readiness, i.e., communities at the no awareness stage require analysis of the historical and cultural issues that support tolerance of drug use, those at the denial and vague awareness stages need specific information about local problems, and communities at the preplanning and preparation stages need information about effective programs, help in identifying resources, and assistance with staff training. In addition, building and maintaining effective programs requires continued evolution of readiness through the stages of initiation, stabilization, confirmation and expansion, and professionalization. Revised and updated scales and methods for assessing community readiness are provided.

Community Health Planning↗

[Immunopathology of the labial salivary glands in Sjögren's syndrome and other autoimmune diseases].

73 minor salivary gland biopsies (lip biopsy) were performed in patients with primary and secundary Sjögren's syndrome and other collagen diseases without sicca syndrome were studied by means of immunohistochemistry. The results were compared to those obtained in sarcoidosis, sialadenitis and normal glands. In all cases of Sjögren's syndrome and of other sialadenites, we could note predominance of T-lymphocytes with an increase of T-Helpers and a T-suppressor ratio superior to 1. Besides, HLA-DR antigen was present in all the activated cells of lymphocytic infiltrates, in endothelial cells and in some epithelial ductal and acinous cells around the infiltrates. This method cannot permit to differentiate Sjögren's syndrome from the other sialadenites. But, it is very useful to appreciate the evolutivity of the disease (increase in B-lymphocytes in the initial period and in evolutive phases) and to detect its change into pseudolymphoma (polyclonal cells with increase in B-cells) and into malignant lymphoma (usually monoclonal B-lymphocytes proliferation).

Autoimmune Diseases↗

[Evolution of ventricular septal defects. Relation to echocardiographic anatomy].

The aim of this study was to analyse the outcome of membranous ventricular septal defects (VSD) with respect to the echocardiographic data obtained during the first year of life. This retrospective series included patients born between January 1st 1986 and December 31st 1995, in the Indre et Loire department, with membranous ventricular septal defects alone or associated with minor abnormalities. The initial echocardiography, an echocardiography performed 2 to 6 months later, one a year later and the final echocardiography were compared. Three groups of VSD were constituted according to their diameter: group I (< or = 3 mm), group II (3-6 mm), and group III (> 6 mm). Depending on the outcome, the patients were classified as spontaneous closure (group A), surgical closure (group B) or persistent VSD (group C). The population comprised 84 children. There were 6 spontaneous deaths, three of which were unexplained, and 7 children were lost to follow-up. After the initial echocardiography, the VSD were classified as group I (38%), group II (26.2%) and group III (35.7%). After the second echocardiogram, 24 VSD changed group (31.5%), by increase (N = 10) or decrease (N = 14) in diameter. Aneurysms of the membranous septum were observed during the first two echocardiographies in 31.2% and 79.3% of VSDs of group I, 31.8% and 70% of VSDs of group II and 6.6% and 3.3% of VSDs of group III (p < 0.01). The average follow-up was 3.1 years (range 1 month-10 years). In group A (N = 22), the mean age of closure of the VSD was 26 months (3 months-7 years). In group B (N = 28), surgery was undertaken at an average age of 10 months (range 3 months-5 years). In group C (N = 21), the VSDs were classified as group I (N = 19) or group II (N = 2) at the last echocardiography. The frequency of aneurysms of the membranous septum in groups A, B and C were respectively 100%, 7.1% and 66.6% (p < 0.01). At the second echocardiographic examination, a significant relationship (p < 0.001) was observed between the diameter of the VSDs and their outcome. The VSDs of group A were associated with aneurysms of the membranous septum more often than those of group C (p < 0.005). The authors conclude that surgery is required in about one third of membranous VSD. At medium term, the others either close spontaneously or become smaller in comparable numbers. The outcome is directly related to the diameter of the VSD and the development of an aneurysm of the membranous septum. During the first 6 months, the dimensions of membranous VSDs change in about 30% of cases with an increase in frequency of aneurysms of the membranous septum.

Female↗

[Evolution of H3 antigen of influenza viruses isolated during 1968-1976].

Influenza viruses type A isolated in 1968--1976 were found to have changes in the content of the antigenic determinant H3. The experiments showed that while in the viruses isolated in 1968--1972 the H3 antigen was dominating, in the A/Port Chalmers/1/73 virus and some viruses isolated in 1975--1976 this antigen became more and more minor. A correlation was observed between the content of H3 antigen in viruses and the capacity of anti-H3 antiserum to inhibit the infectious activity of viruses. The prepared monospecific serum to H3 antigen contained no antibody to the other two antigenic determinants of virus or to neuraminidase and host cell antigen and was completely free from inhibitors. The serum could be used in HI, CFT, and immunodiffusion tests for the analysis of the antigenic composition of newly isolated influenza viruses.

Antigens, Viral↗

Identification of betaIII- and betaIV-tubulin isotypes in cold-adapted microtubules from Atlantic cod (Gadus morhua): antibody mapping and cDNA sequencing.

Isolated microtubule proteins from the Atlantic cod (Gadus morhua) assemble at temperatures between 8 and 30 degrees C. The cold-adaptation is an intrinsic property of the tubulin molecules, but the reason for it is unknown. To increase our knowledge of tubulin diversity and its role in cold-adaptation we have further characterized cod tubulins using alpha- and beta-tubulin site-directed antibodies and antibodies towards posttranslationally modified tubulin. In addition, one cod brain beta-tubulin isotype has been sequenced. In mammals there are five beta-tubulins (betaI, betaII, betaIII, betaIVa and betaIVb) expressed in brain. A cod betaIII-tubulin was identified by its electrophoretic mobility after reduction and carboxymethylation. The betaIII-like tubulin accounted for more than 30% of total brain beta-tubulins, the highest yield yet observed in any animal. This tubulin corresponds most probably with an additional band, designated beta(x), which was found between alpha- and beta-tubulins on SDS-polyacrylamide gels. It was found to be phosphorylated and neurospecific, and constituted about 30% of total cod beta-tubulin isoforms. The sequenced cod tubulin was identified as a betaIV-tubulin, and a betaIV-isotype was stained by a C-terminal specific antibody. The amount of staining indicates that this isotype, as in mammals, only accounts for a minor part of the total brain beta-tubulin. Based on the estimated amounts of betaIII- and betaIV-tubulins in cod brain, our results indicate that cod has at least one additional beta-tubulin isotype and that beta-tubulin diversity evolved early during fish evolution. The sequenced cod betaIV-tubulin had four unique amino acid substitutions when compared to beta-tubulin sequences from other animals, while one substitution was in common with Antarctic rockcod beta-tubulin. Residues 221, Thr to Ser, and 283, Ala to Ser, correspond in the bovine tubulin dimer structure to loops that most probably interact with other tubulin molecules within the microtubule, and might contribute to cold-adaptation of microtubules.

Adaptation, Physiological↗

Characterization of cDNA clones encoding mouse proteinase 3 (myeloblastine) and cathepsin G.

Serine proteases are the most abundant granule constituents of several major hematopoietic cell lineages. Due to their high abundance and their strict tissue specificity they have become important phenotypic cell markers used for studies of various aspects of hematopietic cell development. Using a polymerase chain reaction (PCR)-based strategy for the isolation of trypsin-related serine proteases, we were able to isolate cDNAs for two of the major neutrophil and monocyte serine proteases in the mouse, cathepsin G and mouse protease 3 (myeloblastin). The internal PCR fragments were used as probes to screen a mouse mast cell cDNA library and a cDNA library originating from a mouse monocytic cell line (WEHI-274.1). Full-length cDNAs for mouse cathepsin G and proteinase 3 were isolated and their complete sequences were determined. Northern blot analysis revealed expression of cathepsin G in immature cells of the monocyte macrophage lineage but also in the connective tissue mast cell line MTC. Proteinase 3 was expressed in several cell lines of myelo-monocytic origin and in one B-cell line, but not in any of the other cell lines tested. The isolation of cDNAs for mouse cathepsin G and mouse proteinase 3, together with the previous characterization of the gene for mouse N-elastase, and the entire or partial amino acid sequences for porcine azurocidine, equine N-elastase and proteinase 3, rat, dog, and rabbit cathepsin Gs in evolutionary relatively distantly related mammalian species, indicates that these four members of the serine protease family have been maintained for more than 100 million years of mammalian evolution. This latter finding indicates a strong evolutionary pressure to maintain specific immune functions associated with these neutrophil and monocyte proteases. All amino acid positions of major importance for the cleavage site selection have also been fully conserved between mouse and human proteinase 3 and a few minor changes have occurred between mouse and human cathepsin G.

Amino Acid Sequence↗

T cell receptor clonal diversity following allogeneic marrow grafting.

The advent of methods for exploring T cell clonal diversity in detail by using the reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify the CDR3 segment of the T cell receptor (TCR) Vbeta gene represents a powerful tool for analyzing and monitoring T cell clones that may be responsible for graft-versus-host disease (GVHD) or specific immunity. In this report we describe studies of the posttransplant peripheral blood T cell repertoire in two patients receiving marrow grafts from unrelated donors. One patient received an unmodified T cell replete graft and the second patient received a T cell-depleted marrow graft. Both patients were matched with their donors for HLA-A and -B, but differed for a DRB1 minor mismatch. The patient receiving a TCD graft showed a progressive loss of expression of several Vbeta genes during the first 6 months, although expression of some Vbeta genes appeared transiently following reduction of immune suppression therapy and evidence of acute GVHD. Spectratyping of CDR3 segments revealed evolution of new clones and clonal deletion during the posttransplant period. This method in conjunction with a functional analysis and monitoring of host-reactive clones would provide a new approach for evaluating the activity of immunosuppressive therapy.

Adult↗

Anaerobic digestion of alcohol sulfate (anionic surfactant) rich wastewater--batch experiments. Part I: influence of the surfactant concentration.

Textile wet processing wastewater (e.g., from cotton desizing) contains high concentrations of surfactants as well as readily biodegradable compounds like starch and other carbohydrates. Decyl sulfate (DS, surfactant) and soluble starch were used as model pollutants for biodegradation batch experiments. Very high loadings of the biomass were applied (DS: 21.7-217 g/kg cell dry weight (CDW); starch: 910 g/kg cell dry weight) to study inhibitory effects of the surfactant on the degradation cascade of the biopolymer. The starch hydrolysis was inhibited above sludge loadings of 65 g DS/kg CDW. Acidogenesis was the degradation step with the highest resistance towards inhibitory effects of the surfactant, whereas methanogenesis proved to be the most sensitive. The effects of the surfactant were described by the change of the methane evolution, which was reduced by 50% in 87 days with an addition of 58 g DS/kg CDW. The surfactant caused a high temporary accumulation of intermediates like volatile fatty acids. At the highest loading (217 g DS/kg CDW) the conversion of the substrate to methane was only minor.

Alcohols↗

Early emphysema. Ten years' evolution.

In this study, functional evolution over ten years was evaluated in 13 patients with early emphysema. The diagnosis was made on the basis of a decrease in single-breath DCO (55 +/- 14 percent predicted, mean +/- 1 SD), a loss of elastic recoil (CL,st = 0.76 +/- 0.25 L/cm H2O), and only minor airway obstruction (FEV1 = 87 +/- 13 percent predicted, Sgaw = 0.09 +/- 0.04 cm H2O-1.s-1), and compatible chest radiographs. During the ten years, there was a decrease in FEV1 of 0.89 +/- 0.40 L p less than 0.001), with a range of 0.20 to 1.55 L (which could not clearly be related to smoking habits or to initial lung function), a decrease in elastic recoil (p less than 0.05, with a decrease of Ptp, TLC by 6 +/- 7 cm H2O; p approximately equal to 0.05), an increase in TLC of 0.46 +/- 0.80 1 (p approximately equal to 0.05), and in RV/TLC of 9 +/- 3 percent (p less than 0.001). The resistance of the upstream segment (ratio Ptp/Vmax) increased slightly but generally remained within normal limits. In conclusion, patients with early emphysema resemble those with classic COPD, with a mean yearly decline in FEV1 similar to that in COPD.

Adult↗

The Bucharest multifactorial prevention trial of coronary heart disease. General methodology and risk factor correction after five year follow-up (1971-1977).

Both the intervention and the control group included each 5000 men aged 40-60 years, randomly selected by their home address in five districts of the city of Bucharest. The intervention group underwent an "at entry" examination for risk factor detection (high serum cholesterol, high blood pressure, overweight, diabetes, minor ECG abnormalities, family history) and subsequently a five-year multifactorial intervention aimed to reduce the risk factors. Both groups were followed up in this lapse of time for major end-points: myocardial infarction, stroke, sudden death. The qualitative analysis of the results used ten evolution indices based on a quantal counting and lead to a classification of risk factors which allowed the setting up of a strategy for their correction. The quantitative analysis showed the following decreases between the first and the last examination in the intervention group: for serum cholesterol greater than or equal to 250 mg/dl -17%; for cigarettes/day greater than or equal to 15-53%; for overweight greater than or equal to 30% - 13.57%; for high blood pressure -8%; for the overall risk computed by multiple regression -33.8%.

Adult↗

Characterization of subpopulations (clones and subclones) of the 21 SF strain of Trypanosoma cruzi after long lasting maintenance in the laboratory.

Several studies have shown a clonal structure of Trypanosoma cruzi and its possible correlation with the behavioral heterogeneity of the parasite strains. In the present study, the 21 SF strain, that have been maintained in laboratory by successive passages in mice, for more than 15 years, showing a stability of biological and isoenzymic characteristics has been cloned, with the objective of establishing the characters of its clones and subclones. With the technique of isolation of a single parasite from the blood of infected mice, 5 clones and 14 subclones have been obtained. After four passages into mice, inoculum of 10(5) was obtained for each clone and subclone and inoculated into mice weighing 10 to 12 g. These were used for the study of the biological behavior of the clones: evolution of parasitemia, morphology of blood forms and host mortality. For isoenzymic characterization, the clones and subclones were analyzed for ALAT, ASAT, GPI and PGM enzymes. Results have shown that the 5 clones and the 14 subclones disclosed a biological behavior similar to the parental strain, with minor variability of the parasitemic profiles and also the same isoenzymic patterns. These results confirm the stability of the 21 SF strain and indicate a clonal homogeneity of its populations. This is compatible with the hypothesis that the T. cruzi strains represent an equilibrium of either homogenous or heterogeneous populations.

Animals↗