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At least 55 records · Page 3Linked to original sources
PubMed2026

Experimental evolution reveals genetic routes for adaptive loss of the antibacterial type VI secretion system.

The type VI secretion system (T6SS) is a contractile nanomachine used by Gram-negative bacteria to deliver effector proteins into target cells, contributing to both interbacterial competition and pathogenesis. Although T6SS gene clusters are present in recently isolated commensal and pathogenic Escherichia coli strains, they are absent from classical laboratory strains that have been propagated for decades in pure cultures, suggesting that T6SS can be lost in the absence of competition. Here, we combined experimental evolution with whole-genome sequencing to track the fate of the enteroaggregative Escherichia coli (EAEC) Sci1 T6SS during competition with either T6SS-susceptible or T6SS-immune bacteria. After ∼640 generations, T6SS activity was largely maintained during competition with T6SS-susceptible bacteria, whereas ∼90% of clones evolved with T6SS-immune bacteria lost or attenuated T6SS activity through diverse mutations within the sci1 promoter, essential T6SS structural genes, or the rfaH transcriptional antiterminator. We identified two RfaH-binding ops elements within the sci1 cluster, revealing antitermination as a regulatory element of EAEC T6SS transcription, which is conserved among Enterobacteriaceae. Our findings highlight how experimental evolution can reveal the selective forces shaping T6SS maintenance and identify new regulatory components controlling its activity.

Journal Article↗
PubMed1991

Evolution of the complement system.

The ancestral form of the alternative pathway of complement activation probably originated as a primitive independent immune system. Subsequent evolution of an adaptive immune response drove the specialization of the classical pathway to connect antibody-mediated nonself recognition to the complement-dependent effector mechanisms. In this article Timothy Farries and John Atkinson consider how the contemporary complexity arose by a succession of credible alterations at the genetic level, and the selective advantages provided at each step.

Biological Evolution↗
PubMed2025

Diversification of an emerging bacterial plant pathogen; insights into the global spread of Xanthomonas euvesicatoria pv. perforans.

Emerging and re-emerging plant diseases continue to present multifarious threats to global food security. Considerable recent efforts are therefore being channeled towards understanding the nature of pathogen emergence, their spread and evolution. Xanthomonas euvesicatoria pv. perforans (Xep), one of the causal agents of bacterial spot of tomato, rapidly emerged and displaced other bacterial spot xanthomonads in many tomato production regions around the world. In less than three decades, it has become a dominant xanthomonad pathogen in tomato production systems across the world and presents a compelling example for understanding diversification of recently emerged bacterial plant pathogens. Although Xep has been continuously monitored in Florida since its discovery, the global population structure and evolution at the genome-scale is yet to be fully explored. The objectives of this work were to determine genetic diversity globally to ascertain if different tomato production regions contain genetically distinct Xep populations, to examine genetic relatedness of strains collected in tomato seed production areas in East Asia and other production regions, and to evaluate variation in type III secretion effectors, which are critical pathogenicity and virulence factors, in relationship to population structure. We used genome data from 270 strains from 13 countries for phylogenetic analysis and characterization of type III effector gene diversity among strains. Our results showed notable genetic diversity in the pathogen. We found genetically similar strains in distant tomato production regions, including seed production regions, and diversification over the past 100 years, which is consistent with intercontinental dissemination of the pathogen in hybrid tomato production chains. Evolution of the Xep pangenome, including the acquisition and loss of type III secreted effectors, is apparent within and among phylogenetic lineages. The apparent long-distance movement of the pathogen, together with variants that may not yet be widely distributed, poses risks of emergence of new variants in tomato production.

Xanthomonas↗
PubMed1991

A cellular logic for G protein-coupled ion channel pathways.

A vast array of cellular signal transduction processes arise from combinations of many different types of agonists, receptors, effectors, and coupling molecules such as heterotrimeric G proteins or protein kinases that connect receptors to effectors. Receptors, effectors, G proteins, and kinases are being newly identified at bewildering speeds and in the process it seems that our understanding of how cells respond to specific stimuli may have diminished just as we lose sight of the forest when we are buried in the trees. Evolution would suggest that there may be a logic to the response provoked by a given stimulus and, using our recently acquired knowledge of G protein pathways between receptors and ion channel effectors, I will attempt to decipher what the underlying logic might be.

Animals↗
PubMed2023

Evolution and assembly of Anopheles aquasalis's immune genes: primary malaria vector of coastal Central and South America and the Caribbean Islands.

Anophelines are vectors of malaria, the deadliest disease worldwide transmitted by mosquitoes. The availability of genomic data from various Anopheles species allowed evolutionary comparisons of the immune response genes in search of alternative vector control of the malarial parasites. Now, with the Anopheles aquasalis genome, it was possible to obtain more information about the evolution of the immune response genes. Anopheles aquasalis has 278 immune genes in 24 families or groups. Comparatively, the American anophelines possess fewer genes than Anopheles gambiae s. s., the most dangerous African vector. The most remarkable differences were found in the pathogen recognition and modulation families like FREPs, CLIP and C-type lectins. Even so, genes related to the modulation of the expression of effectors in response to pathogens and gene families that control the production of reactive oxygen species were more conserved. Overall, the results show a variable pattern of evolution in the immune response genes in the anopheline species. Environmental factors, such as exposure to different pathogens and differences in the microbiota composition, could shape the expression of this group of genes. The results presented here will contribute to a better knowledge of the Neotropical vector and open opportunities for malaria control in the endemic-affected areas of the New World.

Animals↗
PubMed1987

[Anti-leukemia resistance and growth-regulating molecules in hematopoietic tissue].

The analyzed data from literature suggest that the growth-regulating molecules of the hematopoietic tissue are a part of the antileukemic defence system of the body. This component of the antitumour resistance is the first one formed during the multicellular organism evolution. It is of special significance in the tissue stimulated to proliferation in which the number of antiblastic defence cell effectors diminishes in the regenerating tissue while the number of progenitor cells having the oncogenic potential increases.

Growth Substances↗
PubMed1990

["T" lymphocytes. Their role in periodontal disease].

The immune response is now proved to be of great importance in the control of periodontal diseases. The predominant role of T lymphocytes in the mechanisms of specific immunity is admitted and is related to the functions of effectors T cells and T-helper cells, controlling the response of macrophages and the antibody production. The relations between the evolution of the disease and the tissular T/B and T4/T8 ratio and the lymphocyte function tests are discussed.

CD4-Positive T-Lymphocytes↗
PubMed1985

A compilation of analytical data from inhibition studies on DNA polymerases and some of its implications.

In connection with the characterization of two DNA polymerases (DPols) of Chlorella, we have extensively surveyed the literature on inhibition studies on DPols in various eukaryotes. By applying Tamiya's plot (1), we have obtained two parameters for each of the inhibitors, phi- and n-values, which express the enzyme sensitivity to the drug and the number of inhibitor molecules present in the enzyme-inhibitor complex that is principally involved in the inhibition, respectively. By inspecting these parameters for the three mammalian DPols, alpha-, beta-, and gamma-pols, as well as other eukaryotic DPols, we have found that: [1] inhibitors commonly utilized for characterizing various DPols can be classified into two major groups, each having two subgroups, on the basis of a comparison of the phi values among alpha-, beta-, and gamma-pols. Moreover, the grouping seems not to be merely coincidental, but to be intrinsically related to facets of the enzyme reaction, which may be taken to reflect evolutionary differences in DPol structure and function among the three DPols; [2] the remarkable n value, n = 1/2, that has been found for the inhibitors competitive with dCTP in Chlorella DPols has also been detected widely in many other eukaryotic DPols. Based on the first finding as well as many other data on various DPols, we have proposed an evolutionary scenario for eukaryotic DPols. Based on the second finding, we have hypothesized a novel role for dCTP as a cofactor, probably an apparent allosteric effector, in the nucleotide transfer reaction mechanism.

Aphidicolin↗
PubMed1989

Lessons from past experience in cancer immunotherapy and their application to cancer and AIDS treatment and prophylaxis.

Passive immunotherapy which we attempted in 1957 using polyclonal antibodies from immunized donors aggravated tumor evolution: we suspected that blocking by Ig, tumor cell antigen epitopes which are necessary to enhance or even maintain the T-lymphocyte effector role in anti-cancer immunity could be the reason for this tumor aggravation by "specific" antibodies. Today the very limited results of monoclonal antibodies in cancer treatment favors this hypothesis. The aggravation of HIV by (some) antibodies suggests that the same phenomenon may also happen in this condition. In 1957, on the other hand, we described the therapeutically beneficial cytostatic targetting effect of polyclonal antibodies, an effect which has often been quoted and widely confirmed. Does the reason for the poor results of monoclonal antibody targetting in tumor treatment reside in cancer antigen heterogeneity? This is what an experiment we conducted with Olsson on AkR leukemia indicated, suggesting that several monoclonals should be simultaneously combined for most patients, to be determined by the antigenic study not only of each tumor but of each localisation. We shifted our cancer immunotherapy approach to an adoptive form in 1959; a), after establishing partial and transient, then total and permanent allogeneic marrow graft and chimerism in man; b), after describing the graft versus leukemia (GvL) action of the graft versus host (GvH) effect in leukaemic mice; c), and the same phenomenon in humans. Our observations on human allogeneic grafted bone marrow GvH and GvL were statistically confirmed in 1979 by the Seattle group. In the 1970s we attempted to induce strong GvL with weak GvH by replacing allogeneic bone marrow graft by allogeneic lymphocyte transfusions without host conditioning. Remarkable results were registered in mice, and in patients with acute leukaemia--5 complete remissions out of 7 patients who developed moderate GvH, and only 3 out of 70 in those who did not develop GvH. As we now know that CD4-, CD8+ lymphocytes are not all MHCl-restricted, we consider that the allogeneic CTL approach is worth trying as reinforcement treatment of (at least) severe hematopoietic malignancies. If it is indeed worthwhile in some severe neoplasias to include the adoptive form of immunotherapy in the multi-treatment program, the replacement of the patient's bone marrow by engrafted allogeneic stem cells has not been proven necessary, as the persistence in "ALL cured" chemotherapy patients of abnormally differentiated cells does not reduce the expectancy of cure.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1986

Homing receptors and the control of lymphocyte migration.

The traffic of lymphocytes is controlled in part by the selective interaction of circulating lymphocytes with specialized high endothelial venule (HEV) cells at sites of lymphocyte exit from the blood. At least three independent receptor systems are responsible for controlling lymphocyte traffic to different lymphoid organs or to sites of inflammation: one mediates lymphocyte interaction with HEV in peripheral lymph nodes, another in mucosa-associated lymphoid tissues, and a third in inflamed synovium. The receptors mediating lymphocyte recognition of HEV in different organs appear to be structurally related yet antigenically and functionally distinct 90 kD glycoproteins. Receptors for lymph node HEV can function as mammalian lectins, and probably interact with specific carbohydrate ligands on high endothelial cells. Mouse and human homing receptors share both antigenic and structural features, indicating a high conservation of lymphocyte-endothelial recognition systems during evolution. They play an essential part in the immune process by controlling lymphocyte traffic during B- and T-cell differentiation, and by segregating effector cells derived from stimulation in different tissues, thus simultaneously increasing the efficiency of organ-specific immune responses and decreasing possibilities for autoimmune crossreactions. Homing receptors are also expressed by many mouse and human lymphoid neoplasms, and appear to play a role in lymphoma metastasis. Related if not identical receptors are expressed by other leukocyte types, including polymorphonuclear leukocytes, monocytes, and large granular lymphocytes (natural killer cells). Thus lymphocyte homing receptors are members of a family of glycoprotein receptors for endothelium that control the extravasation of lymphocytes as well as other leukocytes, and help regulate both non-specific and specific immune responses in vivo.

Animals↗
PubMed1992

Cytotoxicity and cell death: studies on molluscan cells and evolutionary considerations.

In a previous study we demonstrated the presence of NK-like activity in the mollusc Planorbarius corneus. This activity can be ascribed to round hemocytes that have a morphology similar to that of vertebrate lymphocytes. We show here that this NK-like cytotoxicity is evident in serum-free culture medium. Moreover, the type of death induced by molluscan effector cells on their targets is probably similar to that induced by vertebrate effector cells, i.e. apoptosis or programmed cell death, as assessed by the protective effect exerted by 3-aminobenzamide when both types of effector cells were used.

Animals↗
PubMed1989

Evolution of vertebrate motor systems for acoustic and electric communication: peripheral and central elements.

Among vertebrates, there are a number of different neuromuscular systems specialized for the production of acoustic and electric social communication signals. Each system involves distinct sets of striated muscles that are derived from paraxial mesodermal somites and are components of a peripheral effector or 'communication organ': the larynx and syrinx of tetrapods, the sonic swim bladder and electric organ of fishes. Each of these systems further exhibits species-typical characters ranging from the number of muscles involved to myofibrillar architecture. Given that communication uses striated muscle, its circuitry is seen to represent a modification of existing motor systems. Thus, it is not surprising that these systems share several features suggesting that common mechanical or developmental factors influence their evolution. Of prime importance in comparing central communication circuitry between fishes and tetrapods is that among tetrapods the sound-generating organs are a part of the ventilatory system and so their activity must be coordinated with other sets of neuromuscular units. Differences in the central pattern of circuitry are thus expected between fishes and tetrapods, as well as among tetrapods themselves, since ventilation mechanisms differ between taxa. Moreover, birds have independently evolved a vocal syrinx which is distinctly separate from their larynx.

Animal Communication↗
PubMed1983

[Psychotic anxiety and neurotic anxiety. Qualitative or quantitative difference].

We examined successively the different possible approaches to pathological anxiety. In clinical practice, it is easy to distinguish, in qualitative and quantitative terms, between neurotic and psychotic anxiety, the difference being obvious to any practising psychiatrist. A psychopathological approach, however, raises some doubt as to whether the answer is so obvious, and leads us to pose two questions: 1) Is it still possible to have a unitary conception of pathological anxiety, commonly considered as a central element to all forms of psychopathological expression? 2) Since anxiety is an emotion which can be felt by any normal as well as pathological individual, should we consider anxiety to be different when it is expressed in different states - neurosis, psychosis or even border states - by different types of symbolization , depending on the organization of the state? The present advances in pharmacoclinical research, using pharmacological agents as modifying agents for behaviour patterns with specific action mechanisms, enable us to carry the debate further by distinguishing clinical phenomena and neurobiological effector mechanisms. It also shows that within the various established clinical types, several pathological syndromes may be involved, each having different symptoms and its own distinct evolution, and requiring different, more specific treatment. This leads us to rethink the classical distinctions, to refine our semiology, and to familiarize ourselves with the use of chemotherapy, particularly as a "behaviour analyzer", able to teach us something about the different types of anxious behaviour and about the neurobiological mechanisms which are specifically modified by these pharmacological agents.

Anti-Anxiety Agents↗
PubMed1987

DNA polymorphism of MHC III genes in inbred and wild mouse strains.

Genes encoding the second component (C2), factor B, and complement protein C4 and Slp (sex-limited protein) are members of the major histocompatibility complex class III gene cluster. In this report we describe isolation of a mouse C2 cDNA clone and its use together with factor B and C4 cDNA clones to examine the S region in a panel of 42 haplotypes in laboratory and wild mice representing 5 species and subspecies of Mus. Conservation of the C2 factor B gene duplex was evidenced by relatively limited polymorphism associated with speciation and nucleotide sequence homology between mouse and human C2 and factor B. The C4-Slp gene duplex, on the other hand, showed extensive polymorphism by DNA blot analysis. This polymorphism correlated poorly with the C2/factor B restriction fragment length polymorphism, suggesting independent evolution of these two segments of the S region. Taken together, these data will be of particular importance in studies of mouse strains with abnormal regulation of immune effector systems since the class III gene products are essential for activation of the complement cascade.

Amino Acid Sequence↗
PubMedDate not supplied

[Role of oxygen in the vital activity of aerobic organisms].

New experimental data that underlie construction of an adaptive-metabolic conception as to curative effect of hyperbaric oxygenation are systematized in the aspect of evolution. Oxygen under high pressure (300 kPa, 60 min) exerts a specific effect on functions of redox and antiredox systems and nonspecific effect determining adaptation mechanisms of functional (regulatory, effector), metabolic (bioenergy, detoxication, biosynthetic) and morphogenetic (cellular and intracellular regeneration) types at different (hyper-, normo- and hypobiotic) levels of vital activity as dependent on the metabolic activity of the functional structures under pathology conditions.

Adaptation, Physiological↗
PubMed1992

Molecular adaptation of hemoglobin function in mammals.

Vertebrate hemoglobins are tetramers made of two pairs of alpha and beta subunits each containing a hydrophobic pocket where a heme molecule binds tightly and allows for the reversible binding of oxygen. Both tertiary and quaternary structures are ideally suited for the loading and unloading of oxygen necessary for the metabolic requirements of the organisms. Starting from a single ancestor hemoglobin subunit, evolutionary processes have led to heterologous tetramers exhibiting a moderate oxygen affinity due to heme-heme interaction (allosteric mechanism) which may be further modulated through electrostatic interactions with chloride and/or organophosphate anions present in the red cells. These effectors, which bind preferentially to the deoxy-Hb tetramers at a distance from the heme groups, play a major role in the adaptation of the respiratory properties of hemoglobin to either allometric-dependent oxygen needs or to various hypoxic environments such as altitude, burrowing, or foetal life. In most cases the existence or the strength of the effector-Hb complexes, hence the changes in the allosteric equilibrium, may be ascribed to one or a few mutations of residues at the effector binding sites. Typical examples of these mechanisms are described.

Adaptation, Physiological↗
PubMed1990

Conformational and helicoidal analysis of the molecular dynamics of proteins: "curves," dials and windows for a 50 psec dynamic trajectory of BPTI.

A new procedure for the graphic analysis of molecular dynamics (MD) simulations on proteins is introduced, in which comprehensive visualization of results and pattern recognition is greatly facilitated. The method involves determining the conformational and helicoidal parameters for each structure entering the analysis via the method "Curves," developed for proteins by Sklenar, Etchebest, and Lavery (Proteins: Structure, Function Genet. 6:46-60, 1989) followed by a novel computer graphic display of the results. The graphic display is organized systematically using conformation wheels ("dials") for each torsional parameter and "windows" on the range values assumed by the linear and angular helicoidal parameters, and is present in a form isomorphous with the primary structure per se. The complete time evolution of dynamic structure can then be depicted in a set of four composite figures. Dynamic aspects of secondary and tertiary structure are also provided. The procedure is illustrated with an analysis of a 50 psec in vacuo simulation on the 58 residue protein, bovine pancreatic trypsin inhibitor (BPTI), in the vicinity of the local minimum on the energy surface corresponding to a high resolution crystal structure. The time evolution of 272 conformational and 788 helicoidal parameters for BPTI is analyzed. A number of interesting features can be discerned in the analysis, including the dynamic range of conformational and helicoidal motions, the dynamic extent of 2 degrees structure motifs, and the calculated fluctuations in the helix axis. This approach is expected to be useful for a critical analysis of the effects of various assumptions about force field parameters, truncation of potentials, solvation, and electrostatic effects, and can thus contribute to the development of more reliable simulation protocols for proteins. Extensions of the analysis to present differential changes in conformational and helicoidal parameters is expected to be valuable in MD studies of protein complexes with substrates, inhibitors, and effectors and in determining the nature of structural changes in protein-protein interactions.

Biological Evolution↗