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Lung catecholamines and cyclic nucleotides during perinatal development in the rat. Possible relationships with biochemical and morphological differentiation.

In this study, we investigated in parallel the evolution of endogenous catecholamine and cyclic nucleotide levels in lung tissue in the course of normal fetal development of the rat from day 17 of gestation to day 10 postpartum; the findings were correlated with the successive stages of lung differentiation. These were assessed morphologically by electron microscopy, and biochemically by measuring the levels of the main lung tissue phospholipids and studying their fatty acid composition. Dopamine levels were low and always remained under 5 ng/g of wet tissue. Nevertheless, slight rises were observed between days 17 and 19 of gestation (1.8 and 2.78 ng/g, respectively) and between days 21 of gestation and birth (2.56 and 4.25 ng/g, respectively). These changes were significant (P less than 0.05). Norepinephrine (NE) levels first decreased by about 50% between days 17 and 19 of gestation (7.34 and 3.88 ng/g, respectively), (P less than 0.01) and then rose sharply about 4 times until birth (17.24 +/- 3.90 ng/g), and more slowly from then on. On day 10 postpartum, the mean NE level was 34.31 +/- 3.28 ng/g. The levels of the two cyclic nucleotides [cyclic adenosine 3':5'-monophosphate and cyclic guanosine 5'-monophosphate (cGMP)] were quite high on day 17 and remained so until day 19 (cAMP = 220 pmoles /g; cGMP = 20 pmoles/g). From day 19 until day 21, the levels of the two nucleotides decreased (cAMP = 140 pmoles/g; cGMP = 8 pmoles/g; P less than 0.05). During this period, the decrease in cGMP level was about twice that of cAMP. During the last day of gestation, the cAMP level was still decreasing, whereas cGMP was increasing. After birth, the levels of the two cyclic nucleotides rapidly increased to day 5. Between days 5 and 10 postpartum, no significant changes were observed in either cAMP or cGMP levels. The time course of the variations reported suggests that they are related to the maturation processes of lung assessed on the basis of morphological and biochemical criteria. On day 19 of gestation, when the first lamellar bodies appear, large changes occur in the evolution of NE and cyclic nucleotide levels, suggesting that these changes may be related to the onset of surfactant synthesis. On day 21 of gestation, the cAMP and cGMP ratio rises sharply; at the same time, the total phospholipid level is increased by 50%. At this stage, lamellar bodies are actively differentiating within type II pneumocytes and massively released into the fetal airways. The relationships between the variations of the studied biochemical parameters and the maturation processes of lung suggest that dopamine and NE could be involved in surfactant synthesis and release via their second messenger, the cyclic nucleotides. Further investigations are needed to elucidate the mechanisms regulating these changes.

Animals↗

An ultrastructural analysis of endothelial change paralleling platelet aggregation in a light/dye model of microvascular insult.

Those microvascular endothelial events that parallel the evolution of platelet aggregation were evaluated in a well-controlled animal model. Cat pial microvessels were observed through a cranial window while local platelet aggregation was produced by intravenous injection of sodium fluorescein and simultaneous exposure of the pial vessels to light from a filtered mercury lamp that excited the fluorescein. The vessels were fixed in situ when the in vivo observations of a preselected vessel indicated early, intermediate, or advanced aggregation in that vessel. The preselected vessel was then harvested for ultrastructural study together with adjacent vessels from the illuminated field. These vessels and appropriate controls were compared in semiserial thin sections. The onset of platelet aggregation in both venules and arterioles was accompanied by focal endothelial lucency, vacuole formation, luminal membrane rupture, and swelling of the nuclear envelope. These changes were not found in control material. With intermediate aggregation these changes were more common, while with advanced aggregation these abnormalities occurred together with focal endothelial denudation. Thus, in this model denudation occurred only with advanced aggregation and was not a prerequisite for aggregation.

Animals↗

[Microdissection study of the kidneys of reptiles living under different ecologic conditions].

Microdissectional studies on the kidneys of 24 reptilian species living in different habitats show that the relative length of the distal tubuli is higher in animals adapted to a limited water supply and to fresh-water basins, as compared to animals which have unlimited access to water. No regular changes in the length of proximal, intermediate and connective parts were observed. The increase in the length of the distal tubuli occurs simultaneously among different taxonomic groups of reptiles, indicating the existence of parallelism in evolution of their kidneys.

Adaptation, Physiological↗

Red cell aggregability increases with the severity of venous insufficiency.

Several studies have suggested the presence of hemorheological abnormalities in venous insufficiency. The present prospective study was carried out to determine whether the increase in hemorheological disturbances parallels the evolution of the disease. Patients were recruited among ambulant outpatients and classified in 3 evolution stages of venous insufficiency according to the clinical and functional examination. Once a certain number of patients were included, the following successive inclusions were made in order to match for age and sex, in the other stages of venous insufficiency, the previously included patients. Since blood rheology is frequently altered in hypertension, diabetes and several other vascular pathologies, patients with those pathologies were not included. Sixty nine patients with venous insufficiency and 23 healthy subjects were tested, making up twenty three matching sets. Red blood cell (RBC) aggregation and disaggregation were assessed with the SEFAM erythroaggregameter on blood samples adjusted to 40% hematocrit. Statistical analysis showed a significant difference for the aggregation index (p = 0.0001), disaggregation shear rate (p = 0.0001) and fibrinogen (p = 0.006) between the 4 groups. Aggregability parameters increased gradually with the evolution of the disease, while the fibrinogen rise was significant only when varicose veins were present (stages 2 and 3). This progressive rise in RBC aggregability with the aggravation of venous insufficiency, by superimposing to the haemodynamic deficit, is likely to induce the formation of RBC aggregates in vivo, to perpetuate venous stasis and to contribute to the development of severe skin damages.

Blood Viscosity↗

[Evolution of the surgery of cancer of the breast].

Multiple technical and strategical improvements have modified surgical management of breast cancer. Screening mamographies are able to focus small tumors in which excision eventually after percutaneous biopsy can necessitate two surgical procedures. Reduction of axillary dissection in these small lesions can benefit from sentinel node biopsy technique. Immediate or delayed breast reconstruction reduces the mutilation of the mastectomies with their psycho-social disaster. Technically these reconstruction requires a multidisciplinary approach and psychological support. These surgical evolutions in parallel with other therapies for breast cancer developed with two major points: necessity of a good local control for cure, multidisciplinary approach which makes surgeons reals oncologists.

Breast Neoplasms↗

Plasmatic amino acids in kidney transplantation in children.

We studied the evolution of plasma amino acid levels in children with chronic kidney failure after undergoing a renal transplantation. Plasma amino acid profile was studied in 10 children just before surgery, at admission in paediatric intensive care unit and 4, 8, 12, 24, 48 and 72 h after transplantation. Previous to the graft, plasma levels of glutamic acid (p < 0.01), hydroxyproline (p < 0.01), citrulline (p < 0.01) and arginine (p < 0.05) were significantly increased, whereas plasma levels of serine (p < 0.01), glutamine (p < 0.03), threonine (p < 0.01), tyrosine (p < 0.01), valine (p < 0.01), leucine (p < 0.01), tryptophan (p < 0.01), branched amino acids (BCAA) (p < 0.01), aromatic amino acids (AAA) (p < 0.01) and essential amino acids (EAA) (p < 0.01) were decreased in relation to control children. The amino acid profile evolution run parallel to the settle down of renal function parameters. Within 72 h after surgery, even before in some cases, all amino acids except tryptophan and arginine reached normal levels.

Adolescent↗

Long-read sequencing of single cell-derived melanoma subclones reveals divergent and parallel genomic and epigenomic evolutionary trajectories.

Tumor evolution is driven by various mutational processes, ranging from single-nucleotide variants (SNVs) to large structural variants (SVs) to dynamic shifts in DNA methylation. Current short-read sequencing methods struggle to accurately capture the full spectrum of these genomic and epigenomic alterations due to inherent technical limitations. To overcome that, here we introduce an approach for long-read sequencing of single-cell derived subclones, and use it to profile 23 subclones of a mouse melanoma cell line, characterized with distinct growth phenotypes and treatment responses. We develop a computational framework for harmonization and joint analysis of different variant types in the evolutionary context. Uniquely, our framework enables detection of recurrent amplifications of putative driver genes, generated by independent SVs across different lineages, suggesting parallel evolution. In addition, our approach revealed gradual and lineage-specific methylation changes associated with aggressive clonal phenotypes. We also show our set of phylogeny-constrained variant calls along with openly released sequencing data can be a valuable resource for the development of new computational methods.

Journal Article↗

P systems with deadlock.

Rewriting P systems with parallel application of evolution rules, as defined in Besozzi et al. [Parallel rewriting P systems with deadlock. In: Hagiya, M., Ohuchi, A. (Eds.), Pre-Proceedings of DNA8 Conference, Hokkaido University, Japan, June 2002a, pp. 171-183], are considered here. Different kinds of parallelism methods are defined for string rewriting. The notion of deadlock is then introduced to describe situations where rules with mixed target indications are simultaneously applied to a common string. The generative power of parallel P systems with deadlock is analyzed, with respect to Lindenmayer systems, and some relations among different types of parallel P systems with or without deadlock, allowing to rewrite all occurrences of a single symbol, or all the symbols applying either any of the rules or only those belonging to a specific set (table) of rules are studied. Some open problems are also formulated.

Algorithms↗

Bacterial evasion of innate defense at epithelial linings.

The evolution of multicellular organisms has been, and continues to be, paralleled by the evolution of the surrounding microbial flora. This intimate coexistence between higher host organisms and microbes has generated a myriad of adaptation strategies at both sides to cope with, or even benefit from the given conditions. On the host side, the development of an effective immune defence system allowed the maintenance of an astonishingly stable homeostasis on many body sites, and even the establishment of sterile surfaces at vulnerable anatomical sites. On the other hand, microbial diversity has led to the establishment of a large number of microbial life styles that allow persistence and proliferation in the presence of host defense mechanisms. The following review describes bacterial strategies to circumvent or modify host defenses that operate at the epithelial lining. It illustrates the enormous diversity of mechanisms that are part of the complex interplay between microbial organisms and the host. It also reflects the dramatic progress made in the understanding of the mammalian immune defense system which many times has been initiated by the surprising results from the study of microbial pathogenesis.

Animals↗

The crystal structure of an ADP complex of Bacillus subtilis pyridoxal kinase provides evidence for the parallel emergence of enzyme activity during evolution.

Pyridoxal kinase catalyses the phosphorylation of pyridoxal, pyridoxine and pyridoxamine to their 5' phosphates and plays an important role in the pyridoxal 5' phosphate salvage pathway. The crystal structure of a dimeric pyridoxal kinase from Bacillus subtilis has been solved in complex with ADP to 2.8 A resolution. Analysis of the structure suggests that binding of the nucleotide induces the ordering of two loops, which operate independently to close a flap on the active site. Comparisons with other ribokinase superfamily members reveal that B. subtilis pyridoxal kinase is more closely related in both sequence and structure to the family of HMPP kinases than to other pyridoxal kinases, suggesting that this structure represents the first for a novel family of "HMPP kinase-like" pyridoxal kinases. Moreover this further suggests that this enzyme activity has evolved independently on multiple occasions from within the ribokinase superfamily.

Adenosine Diphosphate↗

Stable myocardial function and endocrine dysfunction during experimental brain death.

BACKGROUND: The origin of cardiac impairment during brain death (BD) is controversial. Using a pig experimental model we sought to assess hormonal changes during the first stage of brain death and how these changes contribute to hemodynamic alteration and myocardial dysfunction. METHODS: Twenty-two pigs were randomized into 2 groups: a control (C) group and a BD group. BD was induced by sub-dural inflation of a balloon catheter. Micromanometers and ultrasonic flow probes were placed on the myocardium to measure cardiovascular parameters. Blood samples and hemodynamic parameters were analyzed before and after induction of BD. RESULTS: A biphasic release of catecholamines was observed, with an initial peak occurring 1 minute after BD induction, followed by a second peak at 60 minutes. Similarly, a biphasic evolution of dP/dt(max) and systolic blood pressure (SBP) was observed at BD, in parallel with catecholamine evolution. In the BD group, both cortisol and aldosterone decreased progressively over time. Circulating triiodothyronine (T3), levothyroxine (T4), prolactin and melatonin concentrations were similar to those of the control group. The difference in arteriovenous (AV) lactate level in arterial and coronary sinus blood was not significantly different between the 2 groups, suggesting an absence of myocardial ischemia. Furthermore, myocardial contractility was not altered during the 3 hours of BD. CONCLUSIONS: During the initial period after induction of brain death, cerebral and thyroid hormones remained stable while cortico- and medullo-surrenal hormones varied significantly. We suggest that suprarenal gland impairment is among the first events occurring during brain death. Paradoxically, hemodynamic parameters and myocardial function were not found to be altered.

Animals↗

Mitochondrial DNA variability in Poles and Russians.

Mitochondrial DNA (mtDNA) sequence variation was examined in Poles (from the Pomerania-Kujawy region; n = 436) and Russians (from three different regions of the European part of Russia; n = 201), for which the two hypervariable segments (HVS I and HVS II) and haplogroup-specific coding region sites were analyzed. The use of mtDNA coding region RFLP analysis made it possible to distinguish parallel mutations that occurred at particular sites in the HVS I and II regions during mtDNA evolution. In total, parallel mutations were identified at 73 nucleotide sites in HVS I (17.8%) and 31 sites in HVS II (7.73%). The classification of mitochondrial haplotypes revealed the presence of all major European haplogroups, which were characterized by similar patterns of distribution in Poles and Russians. An analysis of the distribution of the control region haplotypes did not reveal any specific combinations of unique mtDNA haplotypes and their subclusters that clearly distinguish both Poles and Russians from the neighbouring European populations. The only exception is a novel subcluster U4a within subhaplogroup U4, defined by a diagnostic mutation at nucleotide position 310 in HVS II. This subcluster was found in common predominantly between Poles and Russians (at a frequency of 2.3% and 2.0%, respectively) and may therefore have a central-eastern European origin.

DNA, Mitochondrial↗

Evolution of homeotic gene regulation and function in flies and butterflies.

It has been proposed that the evolution of homeotic genes parallels, and to some degree directs, the evolution of segment diversity in the myriapod-insect lineage. But the discovery of discrete Antennapedia complex (ANT-C) and bithorax complex (BX-C) gene members in crustacea, chelicerates, annelids and various insects, as well as in vertebrates, indicates that the expansion and diversification of homeotic genes preceded the diversification of arthropods and insects. How, then, have these genes influenced the evolution of body plans? To address this question, we now examine homeotic gene expression and regulation in butterflies (Lepidoptera), which, unlike flies, possess larval abdominal limbs and two pairs of wings. We show that the difference in larval limb number between these insects results from striking changes in BX-C gene regulation in the butterfly abdomen, and we deduce that the wing-patterning genes regulated by Ultrabithorax have diverged in the course of butterfly and fly evolution. These findings have general implications for the role of homeotic genes in animal evolution.

Amino Acid Sequence↗

Solvable biological evolution models with general fitness functions and multiple mutations in parallel mutation-selection scheme.

In a recent paper [Phys. Rev. E 69, 046121 (2004)]], we used the Suzuki-Trottere formalism to study a quasispecies biological evolution model in a parallel mutation-selection scheme with a single-peak fitness function and a point mutation. In the present paper, we extend such a study to evolution models with more general fitness functions or multiple mutations in the parallel mutation-selection scheme. We give some analytical equations to define the error thresholds for some general cases of mean-field-like or symmetric mutation schemes and fitness functions. We derive some equations for the dynamics in the case of a point mutation and polynomial fitness functions. We derive exact dynamics for two-point mutations, asymmetric mutations, and the four-value spin model with a single-peak fitness function. The same method is applied for the model with a royal road fitness function. We derive the steady-state distribution for the single-peak fitness function.

Biological Evolution↗

Reproductive Isolation due to Divergent Ecological Selection Is Accompanied by Vast Genomic Instability in Experimentally Evolved Yeast Populations.

Populations evolving independently in divergent environments accumulate genetic differences and potentially evolve reproductive isolation as a by-product of divergence. The speed and mechanisms underlying this process are difficult to investigate because we rarely get the opportunity to witness them in natural settings, and histories of selection and gene flow between populations are often unknown. Here, we experimentally evolved yeast for 1000 generations of evolution in both divergent and parallel environments. At regular time points during experimental evolution, we made crosses between parallel- and divergent-evolving populations to measure postzygotic reproductive isolation (gamete viability). We used whole genome population sequencing to determine the mutational load, the number and types of structural variation, and other genomic features of the parent, F1 and F2 intraspecific hybrids. We found evidence for large-scale phenotypic and genome-wide differentiation in response to divergent laboratory selection. Divergent-selected populations produced hybrids with reduced gamete viability-a classic signature of postzygotic reproductive isolation in the form of hybrid breakdown. Parallel-selected populations, on the other hand, remained more reproductively compatible (with exceptions). We found that F2 hybrid genomes contained vast genomic instability, that is, new structural variants (especially insertions, deletions and interchromosomal translocations) that were not observed in parent and F1 genomes, which is likely a result of chromosome missegregation and recombination errors in hybrid meiosis. Our results provide phenotypic and genomic evidence that partial reproductive isolation evolved due to adaptation to divergent environments, consistent with predictions of ecological speciation theory.

Reproductive Isolation↗

Meal to meal energy balance in rats.

Meal to meal energy balance was examined in thirty-eight simultaneous recordings of feeding pattern and O2 consumption in six rats. The mean difference between energy intake in a meal and energy expenditure until the onset of the next meal was found positive at night and negative during day time. At night the excess of meal intake over meal to meal expenditures was decreasing from the beginning to the end of the night and was strongly correlated to meal sizes. During day time meal to meal deficit was decreasing from the beginning to the end of the period but was not correlated to meal sizes. These meal location and size effects on the meal to meal energy balance were not determined by an effect of these factors on metabolic rate. No indication was provided that meal to meal energy balance was influenced by a "meal induced thermogenesis." Rather an evolution from the beginning to the end of the night of the correlation between meal size and durations of meal to meal intervals was found to be parallel to the evolution of positive meal to meal energy balance throughout the night. From these data it is concluded that at night a dual utilization of meal caloric intake (current energy metabolism plus fat storage) and a dual source of fuel during the day (food plus mobilized fats) determine time and mechanism of meal onset.

Animals↗

[Aging and atherosclerosis of human aorta. Comparative evolution of seven glycosyl-transferases and of lactate-dehydrogenase (author's transl)].

Seven glycosyl-transferases and the lactico-dehydrogenase from human aortas were assayed. These aortas were divided in five classes according to the age and in five steps according to the atherogenesis. These enzymic activities do not show any parallelism in their evolution; their variation with age and with atherogenesis is quite different. For example, the N-acetylgalactosaminyl-transferase activity increases with atherogenesis whereas it diminishes with age; on the other hand the lactate-dehydrogenase activity increases with age and decreases with atherogenesis; the sialyl-transferase activity is nearly constant during adulthood while it hardly declines with atherogenesis. These assays suggest: 1) an effect of energy metabolism on the glycosyl-transferase activities; 2) a qualitative and quantitative variation of the glycosaminoglycans biosynthesis; 3) a structural modification of the glucidic part of the glycoproteins which can induce the formation of antigenic sites.

Adolescent↗