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We introduce a simple model of molecular evolution, with a fixed population and a rugged fitness function. We exhibit the analogy between the crossover from a neutralist to an adaptative evolutionary behavior and the percolation transition in genome space.
An analysis of the clinico-anatomical concept "pathomorphosis" allows distinguishing the factors that determine it: social-economical, therapeutic--preventive, ecological and evolutionary adaptive ones. The essence of "the induced pathomorphosis" of tuberculosis is revealed on the basis of epidemiological, clinical and pathological features. The category "pathomorphosis" is reported to be changeable and any weakening of preventive antituberculosis measures will result in the reccurence of classical forms of the disease.
Antifertile effects of PGF2 alpha, PGE2, PGE1, sulprostone and other PGs were evaluated in different pregnancy models in rats, guinea pigs and rhesus monkeys and the underlying mechanisms of action were investigated. Quantitative and qualitative species differences and pregnancy stage dependency were recorded. Basic regulatory differences of the pregnant uterus seem to exist in these species. In early pregnant rats, abortifacient effects were based on luteolytic effects, independent of the PG used. The myometrium was found to be refractory to the injected PG as long as serum progesterone levels were kept high. By contrast, in guinea pigs after the luteoplacental shift of progesterone secretion (tested after day 40 p.c.) and in rhesus monkeys even before this shift (tested day 20 p.c.) abortifacient effects were found to be exerted by direct stimulation of the myometrium. Uterine stimulation was possible in the presence of any level of serum progesterone. The induction of uterine PG synthesis was probably of importance supporting the expulsion. The role of obvious tissue damage within the conceptus remained uncertain. In contrast to rats there seems to be a pre-existing PG-sensitivity of the pregnant myometrium in guinea pigs and primates. In guinea pigs sensitivity slightly increased for E- but not for F-type PG toward term. Oxytocin sensitivity was found to increase by a factor of more than 100 between days 23-63 of pregnancy. Time dependent changes in uterine receptivity to PG and oxytocin may be considered as a regulatory principle which might permit parturition to occur in the presence of progesterone as an evolutionary adaptation to a placental progesterone secretion which cannot be abolished. It was concluded that in the presence of already established gradual uterine responsiveness to PG (and Oxytocin) during gestation efficient blocking mechanisms for uterine PG-formation must exist in order to explain uterine quiescence. Almost complete resistance of pregnancy to oestrogen which exists in humans, monkeys and guinea pigs was considered as to be pharmacological evidence of such a mechanism. The principles of endocrine control of the myometrium and its pharmacology seem similar in guinea pig and primate pregnancy. The guinea pig might therefore provide a relevant model to study potential drug effects on the regulatory balance of the pregnant uterus and also to achieve a better understanding of human uterine physiology.
Interferon exhibits pleotropic effects on homologous cells. Interferons may be used clinically for both antiviral and antitumor therapy. A better understanding of how interferon achieves its hormonal effects should be useful in developing more judicious and specific applications of these natural substances in therapy. Interferon induces increased activity of two enzymes, 2'5'-oligoadenylate synthetase and a protein kinase, that depend on double-stranded RNA for activation. 2'5' A polymerizes ATP into a novel 2'5'-linked oligonucleotide, which in turn can activate a latent cellular nuclease (RNase L) which degrades mRNA. The second dsRNA-dependent enzyme, a protein kinase, phosphorylates a protein of approximately 67,000 daltons as well as the small subunit of eukaryotic initiation factor (eIF-2). The phosphorylation of eIF-2 results in the inhibition of protein synthesis. The extent of sensitivity to exogenous interferon could be influenced by several factors, including the number of cell surface receptors for interferon and the rate and efficiency at which ligand binding and "processing" is achieved. Prostaglandins, cyclic nucleotides, and oxygen-free radicals could participate in modulation of interferon action at this level. Interferon induces specific changes in the composition of membrane lipids. These changes included loss of unsaturated fatty acids from phospholipids, significant increases in levels of unesterified fatty acids, and moderate increases in concentrations of triglycerides and cholesterol esters. The changes were absent in cells treated with interferon in the presence of inhibitors of fatty acid cyclooxygenase or superoxide dismutase. Whether or not interferon-associated lipid changes directly participate in interferon action is not yet clear. Apparent diversity in its mechanistic approach to virus inhibition may be the key to the success of interferon as a wide-spectrum antiviral agent. Heterogeneity in molecular species of interferon may signify its molecular evolutionary adaptations to specific needs and the eventual development of a "fool-proof" system that we now perceive as the "interferon-system." The observed pleotropic effects may be due to linkage to a broader cellular machinery that operates to identify and effectively handle "foreign" substances.
This long term project is aimed to study the following points: 1. Evolutionary adaptation to high altitude. 2. Population genetics of high altitude populations and 3. Mechanisms of resistance to malaria in some of these. The study suggests that the Sherpa of Nepal and the Quechua of Peru, living at altitude about 4000m, may have adapted to low oxygen pressure. The results of biochemical marker studies show that the Himalayan populations may remain genetically separated even when sharing the same village. Studies relating to resistance to falciparum malaria indicate that the immunity, conferred on the Tharu against malaria, may not involve erythrocytes exclusively.
The model for the virus-cell interaction, based on von Neumann's theory of Self-Reproducing Automata, can be improved to consider the evolutionary adaptation which result from the interaction between structures subject to evolution. Theoretical considerations derived from the model are discussed.
Protein C is a vitamin K-dependent serine protease zymogen that upon activation inhibits the coagulation cascade by inactivating factors Va and VIIIa. In an attempt to improve the anticoagulant activity of activated protein C (APC), we have prepared a mutant of protein C in mammalian cells in which Glu at position 192 (chymotrypsin numbering system) has been replaced with Gln (PC E192Q). Our strategy is based on the observation that the same substitution in thrombin improves the catalytic activity toward natural and synthetic substrates that contain Asp residues at P3 and P3'. Since factor Va also has an Asp at position P3 in the APC cleavage site of the factor Va heavy chain, we hypothesized that APC E192Q would inactivate factor Va more rapidly than wild type APC. The mutant inactivated factor Va approximately 2-3-fold faster than wild type. In plasma the mutant exhibited slightly less anticoagulant activity than wild type enzyme. Further characterization revealed that APC E192Q is inhibited 280 times faster than APC by alpha 1-antitrypsin (K2 = 2.8 x 10(3) M-1S-1 versus 10 M-1 S-1), and unlike APC, APC E192Q is inhibited by antithrombin III in the presence of heparin (K2 = 1.17 x 10(3) M-1 S-1) M-1 S-1) and absence of heparin (K2 = 57 M-1 S-1). Ca2+ increased K2 more than 4-fold with or without heparin. Unlike wild type APC, APC E192Q was effectively inhibited by pancreatic trypsin inhibitor (Ki = 10.6 +/- 0.26 nM) and tissue factor pathway inhibitor (58 +/- 5 nM). Like factor Xa, APC E192Q rapidly processed factor IX to factor IX alpha. These observations suggest that even though Glu at position 192 is not an optimal residue for catalyzing factor Va inactivation, it is an evolutionary adaptation to slow inhibition by plasma protease inhibitors.
Although Helen Deutsch's The Psychology of Women contains a wealth of descriptive material about women's problems, the methodology employed by Deutsch in reaching her conclusions about femininity is marred in several ways. Her evolutionary-adaptational bias and natural science approach led to the attribution of questionable biological bases to behavior and to the neglect of social factors and learning. Her concepts and language reveal an unquestioning adoption of Freud's metapsychology and lead to a perception and interpretation of psychological events according to the specific cast of that approach. She confuses her values with definition and observation. A re-examination of the thought of Deutsch seems fitting in these days of ever more extensive reconsideration of the views of Freud and other major psychoanalytic thinkers on the psychology of women. In addition to furthering our understanding of her insights, the study of Deutsch's methodology and its pitfalls contributes to a more critical understanding of the values and preconceptions that influence popular thinking about women and to a deeper grasp of problems inherent in psychoanalytic methodology.
Immune privilege is finally emerging from the curiosity shop into the mainstream of immunology. Immune privileged tissues and sites play a critical role in creating the privileged status, in part by creating peripheral tolerance among antigen-specific T and B cells. While the old idea of "antigen sequestration behind blood: tissue barriers and at sites without efferent lymphatics" seems effete, it appears that a novel view of antigen sequestration is emerging that requires that both immunologic ignorance and peripheral tolerance be considered as relevant to the privileged state. We have argued that immune privilege is an evolutionary adaptation that enables "vulnerable" tissues to arrange for immune protection without suffering the consequences of immunopathogenic damage. In the case of the eye (our organ of interest), privilege enables the eye to avoid immunogenic inflammation. For this specialized organ of sense, inflammation is an unavoidable cause of blindness because inflammation disrupts microanatomic arrangements, and maintenance of the microanatomy of the visual axis is essential for sight. Because immune privilege requires active participation of the immune system for its induction and its maintenance, and since this participation involves the systemic immune apparatus, the tolerance achieved by antigens placed in privileged sites is actually systemic. Therefore, the strategies that are used by privileged sites and tissues to create tolerance parochially, may actually have relevance for creating tolerance of antigenic materials placed at nonprivileged sites of the body.
Malaria is the most prevalent parasite-transmitted infectious disease in humans, with 300-500 million people infected and 3-5 million persons dying from the disease each year [1]. There is, however, surprisingly little knowledge of the parasite's biology and its evolutionary adaptations to cope with a life as an intracellular parasite within its vertebrate host. This article gives an overview of the parasite's developmental cycle and highlights aspects of the immune response in infected humans and the parasite's mechanisms of immune evasion. In addition, special features of the life cycle of the parasite are presented, especially the invasion process of merozoites into red blood cells. Putative mechanisms of drug action of synthetic antimalaria drugs are discussed as well as hypotheses explaining the development of drug resistance in a variety of parasite strains.
The various stages of Plasmodium falciparum (sporozoites and liver stages, asexual blood stages and gametocytes) each interact in a particular way with the human immune system. Specific immunity against the liver stages is achieved through a coordinated action of CD8 T cells and specific antibodies, the latter in collaboration with NK cells and macrophages. In this reaction, interferon-gamma plays an essential role. A non-specific "concomitant" immunity against sporozoites is based on a cytokine reaction, elicited by the blood stages. In practice, the high variability in the immunogenic structures of the sporozoite precludes completely protection against recurrent infections. The spleen macrophages have a pivotal role in the immune defense against the asexual blood stages. The elimination of merozoites and parasitized red blood cells (RBC) is facilitated by specific antibodies, produced under the control of CD4 T cells. There are, however, multiple mechanisms of immune deviation, suppression and evolutionary adaptation, which inhibit a sterilizing immunity against the blood stages. Nevertheless, symptoms may be absent in exposed adults, even when parasitemia persists. This clinical resistance, however, is relatively short-lived, once exposition is interrupted. The observation that HIV infection has no adverse effect on malaria also is a remarkable but consistent finding. All these data indicate that a strong T cell-mediated immune memory is absent in human P. falciparum infections. Cerebral malaria and some other serious complications are the consequence of insufficient elimination of parasitized erythrocytes by the spleen, presumably in combination with parasite factors (particular variant surface structures) and with human host genetics (HLA type, blood group etc.). Parasitized RBC massively stick to the endothelium of the micro-vessels and non-parasitized RBC roset around the parasitized ones. Eventually, serious problems in the micro-perfusion and in the local metabolism occur and organ failure may finally ensue. The immune reaction against the surface-antigens of the sexual stage is limited and insufficient, most probably for similar reasons as in the asexual stages. Internal structures of the gametocytes, however, are highly immunogenic, but, unfortunately. Normally cannot be reached by the immune system. Based on these fundamental data, some of the perspectives of vaccination and new therapeutic tools are critically discussed.
The Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (CYT-18 protein) functions in splicing the N. crassa mitochondrial large rRNA intron by stabilizing the catalytically active structure of the intron core. Here, a comprehensive study of N. crassa mtDNA group I introns identified two additional introns, cob-I2 and the ND1 intron, that are dependent on CYT-18 for splicing in vitro and in vivo. The other seven N. crassa mtDNA group I introns are not CYT-18-dependent and include five that self-splice and two that do not splice under any conditions examined. Some of these introns may require maturases or other proteins for efficient splicing. All but one of the non-CYT-18-dependent introns contain large peripheral extensions of the P5 stem, related to the P5abc structure that blocks CYT-18 binding to the Tetrahymena large rRNA intron. The remaining non-CYT-18-dependent intron, cob-I1, contains a long, peripheral extension of the P9 stem, denoted P9.1, which also impedes CYT-18 binding. Detailed analysis of the CYT-18-dependent ND1 intron showed that two 3' splice sites are used in vitro and in vivo. The proximal, alternative 3' splice site brings the intron open reading frame, which potentially encodes a mobility endonuclease, in frame with the upstream exon, possibly providing a means of expression. Considered together, our results show that group I introns in N. crassa mitochondria use a variety of strategies involving different proteins and/or RNA structures to assist splicing, and they support the hypothesis that CYT-18 and the peripheral RNA structure P5abc are alternative evolutionary adaptations for stabilizing the active structure of the intron core.
In most of the world's population the ability to digest lactose declines sharply after infancy. High lactose digestion capacity in adults is common only in populations of European and circum-Mediterranean origin and is thought to be an evolutionary adaptation to millennia of drinking milk from domestic livestock. Milk can also be consumed in a processed form, such as cheese or soured milk, which has a reduced lactose content. Two other selective pressures for drinking fresh milk with a high lactose content have been proposed: promotion of calcium uptake in high-latitude populations prone to vitamin-D deficiency and maintainance of water and electrolytes in the body in highly and environments. These three hypotheses are all supported by the geographic distribution of high lactose digestion capacity in adults. However, the relationships between environmental variables and adult lactose digestion capacity are highly confounded by the shared ancestry of many populations whose lactose digestion capacity has been tested. The three hypotheses for the evolution of high adult lactose digestion capacity are tested here using a comparative method of analysis that takes the problem of phylogenetic confounding into account. This analysis supports the hypothesis that high adult lactose digestion capacity is an adaptation to dairying but does not support the hypotheses that lactose digestion capacity is additionally selected for either at high latitudes or in highly arid environments. Furthermore, methods using maximum likelihood are used to show that the evolution of milking preceded the evolution of high lactose digestion.
Repeated multiple skin snips in 18 persons with onchocerciasis from the Sudan-savanna of West Africa suggested the possibility of a seasonal variation in microfilarial concentrations. This variation may be an evolutionary adaptation of the parasite to the climate conditions that affect the seasonal distribution of the vector, but a migration of the microfilariae in the skin layers caused by the Simulium bites cannot be excluded.
Creating artificial life forms through evolutionary robotics faces a "chicken and egg" problem: Learning to control a complex body is dominated by problems specific to its sensors and effectors, while building a body that is controllable assumes the pre-existence of a brain. The idea of coevolution of bodies and brains is becoming popular, but little work has been done in evolution of physical structure because of the lack of a general framework for doing it. Evolution of creatures in simulation has usually resulted in virtual entities that are not buildable, while embodied evolution in actual robotics is constrained by the slow pace of real time. The work we present takes a step in addressing the problem of body evolution by applying evolutionary techniques to the design of structures assembled out of elementary components that stick together. Evolution takes place in a simulator that computes forces and stresses and predicts stability of three-dimensional brick structures. The final printout of our program is a schematic assembly, which is then built physically. We demonstrate the functionality of this approach to robot body building with many evolved artifacts.
Semiterrestrial and terrestrial crabs have evolved multiple strategies for aerial respiration. An uncommon strategy for aerial respiration is seen in porcelain crabs, genus Petrolisthes, where decalcified areas on the meral segments of the walking legs are used as respiratory structures. Here, the evolutionary history and adaptive significance of these structures in porcelain crabs is examined. Interspecific variation in leg membrane size is from 0% to 60% of the surface area of the meral segment. Leg membrane relative size is positively correlated with body size across species but not within one species, Petrolisthes cinctipes. Phylogenetic analyses suggest that leg membranes are ancestral to one of two eastern Pacific Petrolisthes clades. Comparative analyses using phylogenetic independent contrasts indicate a relationship between leg membrane relative size and body size that is phylogenetically independent. In large-bodied intertidal species, whole-animal lactate accumulation during aerial incubation is 200%-300% higher when the leg membranes are obscured, indicating that the leg membranes are functional respiratory structures in these species. Thus, it is possible that leg membranes have facilitated the evolution of larger body sizes by providing additional respiratory surfaces to accommodate the associated higher metabolic demands.
The author has planned this research utilizing two models theoretically supported through biomechanical and mathematical laws, as they were formulated by means of data selected from paleoanthropological literature and his own clinic-instrumental case studies, on patients who were stimulated through manual pressure. The hypothesis was: is the paradoxical advantage reasonable for attaining and validating the mode of habitual, vertically aligned posture among evolutionary human-like beings through a vertical load upon their spine, as it is possible clinically in the course of rehabilitation? For assessing this argument two models, one biomechanical and the other mathematical were made up. They test the above mentioned load, as it reaches the clinically ascertained threshold value for triggering a firm gravitational alignment which is in agreement with bipedal gait. The suitability of the biomechanical model derives from reliability of the successively advancing levels of evolution (Anagenesis) from monkeys, through apes, to humans. This model was selected among the postural behaviours that were roughly antecedent to Hominidae bipedalism. So it was possible to abstract an Ape-like anteriorly sloping being, who under the above described stimulation through a suitable load on his-her neck-trapezius muscle angle is submitted to the flow of vertical forces as they show a tendency to aligning vertically the gravitational centers of head, thorax, abdominal masses. So, the biomechanics of the Ape-like being becomes the biomechanics of a mere Man-like mode of functional firm vertical alignment. The suitability of the mathematical model is in agreement with the reliability of the body of a Man-like being which is likened to a cylinder progressing chiefly through rotational and translational torques. The detailed sequence of the mechanical laws of stationary and dynamic equilibrium of rigid bodies and of elasto-mechanical law leads us to an understanding of abstracted sites as they in the course of human evolution were centering the characteristic osseous changes of humans which became the adaptative changes such as they are shown in fossil remains. The vertical alignment should have been validating through the advantageous carrying of loads of suitable weight. This, in turn, should have contributed to evolution of functional erect posture and gait through minimization of the centralised force-tension by means of a stepwise widening about some muscular attachments. So the nuchal part of the occipital bone widened while the increased capacity of enlarging pelvis of the evolutionary woman became adapted to accepting a larger fetal skull.(ABSTRACT TRUNCATED AT 400 WORDS)
Sea anemones occupy the full depth range of the oceans, yet their evolutionary patterns and adaptive strategies to the enigmatic deep sea have remained contentious and poorly resolved. Here, we assemble genomes (n = 13) and transcriptomes for 15 species collected between 432 and 6,000 m and integrate them with publicly available actiniarian data. We find support for a shallow-water origin of Actiniaria through a framework that emphasizes genome-scale changes associated with habitat transitions. Most strikingly, these changes include repeated dismantling of the circadian toolkit across deep-sea lineages. In addition to convergent gene losses in photo- and temperature-regulatory genes, we find that some deep-sea lineages have experienced recurrent loss or pseudogenization of key meiotic genes (e.g., Meiosin, Ythdc2, Spo11, and Mlh3), suggesting reduced meiotic capacity in some lineages. Despite this extensive genomic erosion, deep-sea anemones exhibit molecular tuning: specific amino acid substitutions improve enzyme performance under low-temperature conditions relevant to the deep sea, while selective expansions of gene families related to neural excitability, membrane systems, and other functions may help maintain physiological performance in this environment. Functional assays in yeast indicate enhanced performance of the deep-sea variants at 4°C. These results define a "loss-optimization-innovation" triad that underlies bathymetric adaptations and may apply to other deep-sea fauna worldwide.