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Conflicting levels of selection in the accumulation of mitochondrial defects in Saccharomyces cerevisiae.

The somatic accumulation of defective mitochondria causes human degenerative syndromes, senescence in fungi, and male sterility in plants. These diverse phenomena may result from conflicts between natural selection at different levels of organization. Such conflicts are fundamental to the evolution of cooperating groups, from cells to populations. We present a model in which defective mitochondrial genomes accumulate because of a within-cell replication advantage when among-cell selection for efficient respiration is relaxed. We tested the model by using experimental populations of the yeast Saccharomyces cerevisiae. We constructed yeast strains that were heteroplasmic for mitochondrial mutations that destroy the ability to respire (the petite phenotype) and followed the accumulation of mitochondrial defects in cultures with different effective population sizes. As predicted by the model, the inability to respire evolved only in small populations of S. cerevisiae, where among-cell selection favoring cells that can respire was reduced relative to within-cell selection favoring parasitic mitochondria. In a control experiment, mitochondrial point mutations that confer resistance to chloramphenicol showed no tendency to change in frequency under any culture conditions. The accumulation of some mitochondrial defects is therefore an evolutionary process, involving multiple levels of selection. The relative intensities of within- and among-cell selection may also explain the tissue specificity of human mitochondrial defects.

Cell Respiration↗

The master equation for neural interaction.

Based on neural interaction equations a random walk model for the stochastic dynamics of a single neuron is introduced. In this model the somatic potential corresponds to a state in the state space and action potentials provide the mechanism causing transitions. Time is made discrete, consisting of small finite increments delta t; assumptions are made about the transitions within such an increment and the associated probabilities are formulated. These quantities depend on delta t and on parameters derived from neural interaction equations. Moreover the model is chosen so that the sequence of somatic potentials is a Markov chain. By appropriately scaling the parameters, in the limit as delta t----0, a master equation for the probability in continuous time is obtained. Depending on the parameters, the master equation describes the evolution of a deterministic, a diffusion, or a discrete process. An interpretation for the diffusion and discrete processes is outlined. The conclusion is that the stochastic equations for neural interaction lead to a master equation representing a diffusion or a discrete process depending on the number, size of synaptic connectivity coefficients, and probability distribution of neural activity. An example is included describing how a master equation may be used to derive properties of the single neuron's output process.

Animals↗

Expression of the viviparous 1 (Pavp1) and p34cdc2 protein kinase (cdc2Pa) genes during somatic embryogenesis in Norway spruce (Picea abies [L.] Karst).

Detailed expression analysis of the Norway spruce (Picea abies [L.] Karst) Viviparous 1 (Pavp1) and p34cdc2 (cdc2Pa) genes was carried out during somatic embryogenesis. Pavp1, a gene associated with embryo development, was expressed in proliferating embryogenic suspension cultures in the absence of exogenous ABA. When somatic embryo formation was promoting by blocking proliferation, Pavp1 expression was reduced. During maturation, exogenous ABA induced increased Pavp1 expression, which peaked at the early cotyledonary stage of somatic embryogenesis. Following partial desiccation of mature somatic embryos at high relative humidity, Pavp1 expression persisted under germination conditions. Pavp1 expression was also detected in non-dormant immature male strobili and dormant terminal buds. These data confirm the functional conservation of Pavp1 during the evolution of seed plants and extend its function beyond the embryo. Cdc2Pa, a gene associated with the cell cycle, was up-regulated when the proliferation of embryogenic cells was blocked. Expression was again up-regulated in early embryogeny and again during germination. The implications of this up-regulation of cdc2Pa are discussed.

Abscisic Acid↗

The modulation of DNA content: proximate causes and ultimate consequences.

The forces responsible for modulating the large-scale features of the genome remain one of the most difficult issues confronting evolutionary biology. Although diversity in chromosomal architecture, nucleotide composition, and genome size has been well documented, there is little understanding of either the evolutionary origins or impact of much of this variation. The 80,000-fold divergence in genome sizes among eukaryotes represents perhaps the greatest challenge for genomic holists. Although some researchers continue to characterize much variation in genome size as a mere by-product of an intragenomic selfish DNA "free-for-all" there is increasing evidence for the primacy of selection in molding genome sizes via impacts on cell size and division rates. Moreover, processes inducing quantum or doubling series variation in gametic or somatic genome sizes are common. These abrupt shifts have broad effects on phenotypic attributes at both cellular and organismal levels and may play an important role in explaining episodes of rapid-or even saltational-character state evolution.

Animals↗

Evaluation of anxiety and depression in childhood migraine.

Childhood migraine can be the expression of an unconscious attempt of the small patient to show a discomfort which is denied through the defence of somatization. We considered a sample of 73 children, 39 males and 34 females suffering from migraine. We evaluated the presence of emotional disorders through diagnostic interviews consisting of one by one submission of the Anxiety Scale Questionnaire for Evolutive Age and the Children Depression Scale Test. Within our sample we are able to distinguish three groups: a first group negative for both anxiety and depressive disorders, thus defined as control group; a second group presenting anxiety depressive disorders and a third one presenting a mostly depressive symptomatology. We found a significantly higher incidence of migraine in male firstborn children belonging to the group with a condition associated to anxiety and depression.

Adolescent↗

Neuropeptide control of the cardiovascular system in fish and reptiles.

Accumulating evidence shows the involvement of neuropeptides in cardiovascular control in mammals as well as non-mammalian species. Our own immunohistochemical studies indicate a sparse innervation only in cyclostomes, holostean fish and lungfish, a more extensive variation and distribution in elasmobranchs and teleosts, and a rich and varied innervation of the cardiovascular system in crocodiles and lizards. Vasoactive intestinal polypeptide (VIP), neuropeptie Y (NPY), gastrin releasing peptide (GRP) and tachykinins are present in most vertebrate groups. VIP is vasodilatory in the Atlantic cod (Gadus morhua) as in most mammalian species, but increases gut vascular resistance in the spiny dogfish (Squalus acanthias). NPY potentiates the effect of noradrenaline on skate (Raja rhina) coronary vessels, suggesting an interaction between adrenergic mechanisms and NPY early in evolution, but studies in the spiny dogfish and the crocodile also demonstrate different mechanisms for the action of NPY and adrenaline in some species. Bombesin/GRP increases flow to the gut in the spiny dogfish by an increase in somatic vascular resistance, while visceral resistance remains unchanged. In the caiman (Caiman crocodylus crocodylus) bombesin causes a shunting of blood from the lung to the gut. Substance P and other tachykinins in general increase flow to the gut, and on some occasions also increase somatic blood flow. Flow in the anastomosis of the crocodile (Crocodylus porosus) gut is increased by substance P. The results presented here are a review of several published and unpublished studies.

Alligators and Crocodiles↗

Rapid evolution of human pseudoautosomal genes and their mouse homologs.

Comparative studies of genes in the pseudoautosomal region (PAR) of human and mouse sex chromosomes have thus far been very limited. The only comparisons that can presently be made indicate that the PARs of humans and mice are not identical in terms of gene content. Here we describe additional comparative studies of human pseudoautosomal genes and their mouse homologs. Using a somatic cell hybrid mapping panel, we have assigned the mouse homolog of the human pseudoautosomal interleukin 3 receptor alpha subunit (IL3RA) gene to mouse Chromosome (Chr) 14. Attempts to clone the mouse homolog of the human pseudoautosomal adenine nucleotide translocase-3 (ANT3) gene resulted in the isolation of the murine homologs of the human ANT1 and ANT2 genes. The mouse Ant1 and Ant2 genes are very similar in sequence to their human homologs, and we have mapped them to mouse Chromosomes (Chrs) (8 and X respectively) that exhibit conserved synteny with the chromosomes on which the human genes are located. In contrast, the homolog of ANT3 appears to be either very divergent or absent from the mouse genome. Southern blot analysis of DNA from a variety of mammalian species shows restricted conservation of human pseudoautosomal genes, a trend that also applies to the two cloned mouse homologs of these genes and to neighboring human genes in distal Xp22.3. Our observations combined with those of other workers lead us to propose a model for the evolution of the PAR that includes both rapid sequence evolution and the incremental reduction in size of the region during mammalian evolution.

Animals↗

Love hurts: the evolution of empathic concern through the encephalization of nociceptive capacity.

Empathic concern for others is an essential motive for challenges of self-regulation at all developmental stages. A child who never develops the capacity for empathic concern may become an ineffective parent, such that developmental psychopathology propagates across generations. We draw on evidence and theory by Panksepp and associates that indicates that infant-mother bonding is mediated by opiate mechanisms. We review the neural systems of pain perception and find these are closely aligned with those for attentional and cognitive self-regulation. Analysis of the limbic and neocortical representations for interpersonal reasoning suggests there are important contributions from visceral, affective, and somatic and cognitive levels. We draw on modern learning theory to propose a critical role for frustration training in development to allow the child to achieve the capacity for tolerating psychological pain that allows effective empathic concern in later relationships.

Attention↗

Degeneration after sexual differentiation in hydra and its relevance to the evolution of aging.

Aging occurs in most multicellular animals, yet some primitive animals do not show any sign of aging. This raises the following question: How have metazoans acquired the trait of aging in the course of evolution? Comparative studies of various species have provided a clue to this question by showing that sexually reproducing organisms predominantly undergo aging. The evolutionary theory "pleiotropy" also postulates aging as a price for facilitating the reproduction in the early life stage of an organism. For investigating the association between sexual reproduction and aging, a sexual phase-inducible organism in a laboratory would be suitable. One of such organisms is hydra, a genus of Cnidaria. Asexual hydra has been considered to be immortal, but there is the possibility that hydra undergoes aging after sexual reproduction. To search for signs of aging in hydra, we studied sexually differentiated Hydra oligactis at the individual and cellular levels. As a result, we found a significant decline in the capacities for food capture, contractile movements, and reproduction. More importantly, we discovered an exponential increase in the mortality rate of the population. These observations suggest that the degenerative process in H. oligactis represents the aging process. Furthermore, we found that the number of germ cells increased, whereas the number of somatic cells concomitantly decreased. The observed change of the cell composition is thus consistent with the "pleiotropy" theory of aging.

Animals↗

Structural analysis of substitution patterns in alleles of human immunoglobulin VH genes.

The diversity in repertoires of antibodies (Abs) needed in response to the antigen challenge is produced by evolutionary and somatic processes. The mechanisms operating at a somatic level have been studied in great detail. In contrast, neither the mechanisms nor the strategies of diversification at an evolutionary level have yet been understood in similar detail. Particularly, the substitution patterns in alleles of immunoglobulin genes (Igs) have not been systematically studied. Furthermore, there is a scarcity of studies which link the analysis at a genetic level of the diversification of repertoires with the structural consequences at the protein level of the changes in DNA information. For the purpose of systematically characterizing the strategies of evolutionary diversification through sequence variation at alleles, in this work, we built a database for all the alleles of the IGHV locus in humans reported until now. Based on these data, we performed diverse analyses of substitution patterns and linked these results with studies at the protein level. We found that the sequence diversification in different alleles does not operate with equal intensity for all V genes. Our studies, both of the number of substitutions and of the type of amino acid change per sub-segment of the V-REGION evidenced differences in the selective pressure to which these regions are exposed. The implications of these results for understanding the evolutionary diversification strategies, as well as for the somatic generation of antibody repertoires are discussed.

Alleles↗

Serotonin receptor 1c gene assigned to X chromosome in human (band q24) and mouse (bands D-F4).

In the mammalian nervous system, serotonin (5-hydroxytryptamine) binds to distinct cell surface receptor subtypes that are defined by their ligand binding and effector-coupling properties. The 5HT1c receptor is a G-protein coupled receptor that stimulates phospholipase C-catalyzed hydrolysis of phosphatidylinositol bisphosphate, leading to the mobilization of intracellular calcium and to the activation of protein kinase C. By using somatic cell hybrid analysis and FISH, we have mapped the HTR1C locus to the human X chromosome, band q24 and to the mouse X chromosome region D-F4. Comparison of these map positions offers new insights into the evolution of human and murine X chromosomes. Since HTR1C is expressed in certain parts of the central nervous system and abnormal function of the serotoninergic system has been implicated in affective disorders, obsessive-compulsive disorder and epilepsy, establishing the precise map position of HTR1C is an important first step toward evaluating this locus as a candidate for mutations in these syndromes and in X-linked mental disorders.

Animals↗

Biology of germinal centers in lymphoid tissue.

Germinal centers in lymphoid tissue are the sites of generation of memory B cells undergoing isotype switching and somatic mutation in their Ig genes. Their formation cannot be induced by stimuli other than immunogenic ones. It seems likely that in the function and possibly also in the formation of germinal centers, one important factor is the localization of immune complexes with fixed complement on the surface of follicular dendritic cells. CD4+ T cells, located primarily in the "apical light zones" of the centers, are necessary for germinal center formation. However, their exact role in the process needs clarification, as both cell to cell contact and cytokine production could be involved at different stages of the germinal center generation. These T cells are usually specific for the antigen inducing the germinal center, but they may sometimes respond to other surface components on the B cell surface. In view of the possible stimulatory role of CD4+ T cells in follicular center-derived lymphomas, the functional significance of these T cells in germinal center proliferation is important to unravel. The B cells in germinal centers proliferate extremely rapidly, especially those located in the "dark zones." Many of them undergo apoptosis, particularly in the "basal light zones." The microenvironment of these centers is well suited to the task of expanding and selecting memory B cells of high affinity for the inducing antigen. The interactions of the proliferating B cells with dendritic cells and T cells, unevenly distributed in the various zones of the germinal center, are thought to determine which cells deserve rescue from apoptosis and induction to differentiation into small resting memory B cells. The memory B cells that emerge from the germinal center bear sIg, usually of "switched" isotype, and exhibit somatic mutations in the variable regions of their rearranged Ig genes.

Aging↗

Toxic thyroid adenoma: absence of DNA mutations of the TSH receptor and Gs alpha.

DNA point mutations of the TSH receptor and of the alpha subunit of the stimulatory GTP-binding protein (Gs alpha) have been suggested as major causes of hyperfunctioning thyroid adenomas. However, significant differences in the prevalence of these mutations (from 0.3 to 84%) have been found in different populations. The present study was designed to evaluate further the presence of mutations in discrete fragments of cDNA encoding critical regions of the TSH receptor and of the Gs alpha involved in signal transduction and cAMP production. Genomic DNA extracted from 15 thyroid adenomas and surrounding quiescent thyroid tissues was used as a template to amplify four DNA fragments of TSH receptor and one DNA fragment of Gs alpha. TSH receptor and Gs alpha DNAs were analyzed by a number of techniques. We did not detect any mutations (new or previously described) in our patients. These results confirm that the causes of solitary toxic adenomas are protean, and only some of them may be somatic DNA point mutations. Since the clinical features of solitary toxic adenoma are homogeneous, it could be important to establish the specific molecular defect underlying each case, in order to follow up the patients and to assess their clinical evolution.

Adenoma↗

The brain of the mammal-like reptile Probainognathus jenseni (Therapsida, Cynodontia). A correlative paleo-neoneurological approach to the neocortex at the reptile-mammal transition.

A natural endocranial cast of the South American cynodont Probainognathus jenseni is studied, and an evaluation of the probable nature of the neocortex at the level of certain cynodonts of the Middle Triassic is made, based in the available paleo-neoneurological information. The endocast of Probainognathus shows well developed olfactory bulbs, long cerebral hemispheres, small anterior colliculi and well represented cerebellum and flooculi. The pineal gland may have been located between the caudal hemispheric poles. No parietal foramen exists. The dorsal surface of the cerebral hemispheres shows a slope at the level of the anterior edge of the caudal fourth part, which is interpreted as the posterior limit of the neocortical plate. At the level of the olfactory peduncles, it is visible a stem vessel; one of its branches distributes on the anterior part of the lateral border of the hemisphere. It is advanced the interpretation that this latter vessel could indicate the paleo-neocortical boundary. The analysis of the neoneurological information led the author to suppose that the neocortex of Probainognathus, and surely of other cynodonts of the Middle Triassic, has shown supplementary somatic sensory and motor, visual and auditory representations, and perhaps incipient primary somati sensory and motor ones, advancing a "polymodal cortex", as it is supposed had stem mammals. Moreover, the histostructure of the neocortex at this state of the evolution may have been in a proisocortical-isocortical stage, that is, in the beginnings of the true neocortex. The confrontation of the paleoneurologic with the neoneurologic information led the author to suppose that Triconodon and Ptilodus have had a neocortex, surely more developed than Probainognathus, but that it is not seen in the endocasts at present studied. The quantitative analysis of Probainognathus' endocast, as well as those of other cynodonts, suggest that certain cynodonts of the Middle Triassic were in an advanced state toward endothermy.

Animals↗

Evolution and natural history of chronic lung disease of prematurity.

Chronic lung disease (CLD) of prematurity is a common disorder in preterm infants who were ventilated for respiratory distress syndrome (RDS) at birth. Premature birth, mechanical ventilation and supplemental oxygen are the major risk factors for the development of CLD. Although the exact pathophysiology is unclear, recent evidence suggests that pulmonary inflammation may play a pivotal role in the development of CLD. Histologically, the evolution of CLD can be divided into an early inflammatory phase followed by a subacute and chronic fibroproliferative phase. The early, inflammatory phase of CLD is clinically indistinguishable from RDS. In bronchoalveolar lavage fluid an influx of inflammatory cells and increased levels of cytokines can be found. Pathological examination of the lungs reveals persisting hyaline membranes, necrosis of airway and alveolar epithelium and an influx of inflammatory cells in the lung. In the subacute fibroproliferative or reparative phase of CLD, persistent respiratory distress and hypercapnia are seen and patients require oxygen with or without ventilatory support. Histologically, this phase is characterized by hyperplasia of type II pneumocytes, hypertrophy of bronchial and bronchiolar smooth muscle and interstitial and perialveolar fibrosis. In the chronic fibroproliferative phase (up to 1 yr), airway remodelling occurs. Respiratory distress continues and many patients remain oxygen dependent. Cyanotic spells are frequently seen and chronic hypoxia may lead to pulmonary hypertension and right heart failure. Many patients have severe feeding problems and somatic growth is poor. In surviving patients, persisting lung function abnormalities are found. Airway resistance and airway responsiveness are increased and residual volume (RV) and RV/total lung capacity ratios remain elevated, indicating air trapping. Although lung function improves during childhood, residual abnormalities are still found in young adults, raising concerns about the evolution of pulmonary function in old age.

Adult↗

The historical evolution of the concept of negative symptoms in schizophrenia.

Table IV schematically summarises the models of some important theoreticians in order to indicate the heterogeneity of the conceptual basis for the distinction between positive and negative forms of schizophrenia. Thus, in different terminologies, positive and negative symptoms by Reynolds and Jackson are related to different mental and somatic disturbances. Bleuler mainly judges associations and their possible alterations, particularly by affect. When Berze, through the insufficiency of mental activity, places a negative element into the centre of his schizophrenia theory, he is interested in the conscious mental acts and intentionality. Gruhle, on the other hand, considers the different activity of hyper- and hypo-phases and, as an additional dimension, the comprehensibility of motives. Janzarik, in his dynamistic conception, first of all analyses the positive and negative conditions from the viewpoint of energy and emotion. This simple review advises caution when composing historical positions to a unitarian concept of positive and negative psychoses. Considering the present discussion, however, we find a similar situation with quite different areas, which serve as support for the division into a positive and negative form of schizophrenia. The logic of these tendencies corresponds with the present trend to a multiaxial or multidimensional registration of clinical, psychopathological and biological data. However, the various levels of explanation have questionable relations to each other. According to the clinical model based on natural sciences, we expect an approach to valid entities by an optimisation of the defining criteria which are derived from psychological, somatological and clinical sources (Sass, 1987).(ABSTRACT TRUNCATED AT 250 WORDS)

Europe↗

Sequence similarities of protein kinase substrates and inhibitors with immunoglobulins and model immunoglobulin homologue: cell adhesion molecule from the living fossil sponge Geodia cydonium. Mapping of coherent database similarities and implications for evolution of CDR1 and hypermutation.

Sequences of immunoglobulin (Ig) domains of adhesive molecule GSAMS from the living fossil sponge Geodia cydonium were compared with the important motif of peptide protein kinase substrates and inhibitors (PKSI), detail PKSI sequences, and a common template sequence, derived from structures determined previously. We found the site-restricted sequence similarities to these peptide sequences predominantly in the GSAM Ig1 domain of GSAMS in the domain region related to corresponding Ig similarities detected earlier. Additional sequence block-related analysis revealed the presence of CDR1-like segments within PKSI-related regions and resulted in the detection of increased numbers of hypermutation motifs just in the CDR1-like segment of GSAM Ig1 (GSAM(cdrl.1)). In the following database searches with PKSI-related regions and GSAM(cdr1.1) we looked for: (i) peptide similarities present in the context of Ig domains or related structures in a large range of species from Archaea to Vertebrata, and (ii) some special nucleotide similarities.

Amino Acid Motifs↗

Emergence and evolution of functional heavy-chain antibodies in Camelidae.

Antibodies of jawed-vertebrates are composed of paired heavy (H) and light (L) polypeptide chains. Surprisingly, the sera of camelids, nurse shark and wobbegong shark, and possibly ratfish contain antibodies that lack L-chains. In camelids, these Heavy-chain antibodies (HCAbs) are gamma-isotypes, and are functional in antigen binding. In this review we focus on the dedicated immunoglobulin (Ig) genes that encode the HCAb in Camelidae (camels, dromedaries and llamas), about their origin, and how these camel immunoglobulins evolved and acquire a large and diverse repertoire of antigen binding sites in absence of the H-L combinatorial diversity.

Amino Acid Sequence↗