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PubMed1991

Genetic and environmental modulations of chromosomal stability: their roles in aging and oncogenesis.

The primary objective of this review is to suggest a major role of cytogenetic pathology in the genesis of both the neoplastic phenotype and the senescent phenotype of aging mammalian organisms. It is hypothesized that allelic variation at a number of genetic loci that have the potential to modulate various types of chromosomal mutation could account, in part, for species-specific variations in maximum life-span potentials and the times of onset of characteristic age-related neoplasms. As a corollary to this proposition, attention is directed to the potential importance of environmental clastogens and aneugens as both oncogenic and "gerontogenic" agents. By way of introduction, a series of definitions of our subject material is given (aging, oncogenesis, proliferative homeostasis, point mutation, chromosomal mutation, epimutation, mutagens, clastogens, aneugens, gerontogens). There follows a defense of the view that there is a tight coupling of abnormalities in proliferative homeostasis (including atrophies, hyperplasias, benign neoplasias and malignant neoplasias) with intrinsic biological aging. This view differs from those of other authors who either: 1) believe that, to qualify as a bona fide component of aging, the phenotype in question (in this case, neoplasia) must be "genetically programmed" or 2) insist that the rate of development of the neoplastic phenotype should parallel species-specific Gompertz kinetics for the survival of the population of organisms. After briefly reviewing the classification of chromosomal lesions, we consider evidence for constitutional genetic determinants of chromosomal stability, oncogenesis, and some other aspects of the senescent phenotype, both with respect to interspecific and intraspecific differences. The discussion will include the recent evidence characterizing a human segmental progeroid syndrome (Werner's syndrome) as a deletor mutator strain. A summary of research on environmental chemical clastogens and aneugens is given, showing both discordances and concordances of such assays with assays for point mutagens. An analysis of the literature indicates that there is no statistical evidence for the positive correlations when substances showing effects only at comparatively high concentrations (greater than 1 mM) are excluded from the analysis. Brief mention is also made of the roles of viral agents and ionizing radiation in the genesis of chromosomal mutations. Finally, some possible pathogenetic mechanisms common to chromosomal mutagenicity, oncogenicity and gerontogenicity are considered, including chemical free radicals (active oxygen species), DNA transposition, DNA amplification, DNA glycation, virally induced cell fusion, posttranslational modifications of centromeric and mitotic spindle proteins, and alterations in the metabolism of telomeric DNA.

Aging↗
PubMed2003

The basic biology of apoptosis and its implications for cardiac function and viability.

Apoptosis or programed cell death is a continuous process of destruction of nonfunctional cells. It is a physiologic process whereby the body disposes of unwanted cells by self-destruction and is our utmost defense against damaged cells. There are several pathways leading to programed cell death. Apoptosis is seen in failing, infarcted, and hibernating human hearts, and during open heart surgery. Apoptosis appears to be induced by myocardial ischemia-reperfusion injury and this is reduced by ischemic preconditioning. Antiapoptotic interventions may be a future target for myocardial protection.

Animals↗
PubMed2003

Small GTPase 'Rop': molecular switch for plant defense responses.

The conserved Rho family of GTPases (Rho, Rac, and Cdc42) in fungi and mammals has emerged as a key regulator of diverse cellular activities, such as cytoskeletal rearrangements, programmed cell death, stress-induced signaling, and cell growth and differentiation. In plants, a unique class of Rho-like proteins, most closely related to mammalian Rac, has only been found and termed 'Rop' (Rho-related GTPase from plant [Li et al. (1998) Plant Physiol. 118, 407-417; Yang (2002) Plant Cell 14, S375-S388]). ROPs have been implicated in regulating various plant cellular responses including defense against pathogens. It has been shown that ROPs, like mammalian Rac, trigger hydrogen peroxide production and hence the 'oxidative burst', a crucial component associated with the cell death, most likely via activation of nicotinamide adenine dinucleotide phosphate oxidase in both monocotyledonous and dicotyledonous species. Recent studies have established that ROPs also function as a molecular switch for defense signaling pathway(s) linked with disease resistance. As discerning the defense pathway remains one of the priority research areas in the field of plant biology, this review is therefore particularly focused on recent progresses that have been made towards understanding the plant defense responses mediated by ROPs.

Amino Acid Sequence↗
PubMed2026

Leaf Rust in Rye: From Pathogen Biology to Host Defense and Resistance Breeding.

Leaf rust (LR), caused by Puccinia recondita f. sp. secalis (Prs), is considered one of the most dangerous rye (Secale cereale L.) diseases, causing yield losses exceeding 35%. This review summarizes all currently available data about this disease: pathogen characteristics (including its life cycle, natural variation, and disease symptoms), resistance resources, and the background of the plant immune response at the genome, transcriptome, and metabolome levels. The research conducted so far has allowed for the identification of dozens of genes that play a significant role in the rye immune response to Prs infection. Among them, genes encoding NBS-LRR proteins (including SECCE1Rv1G0014220, the most likely Pr3 candidate), glycosyltransferase, β-1,3-glucanase, 1-deoxy-D-xylulose 5-phosphate synthase, β-1,3-glucanase, UDP-glycosyltransferase, pathogenesis-related protein 1, ammonium transporter, and cytochrome P450 enzymes are candidates for seedling and all-stage resistance, whereas ScLr_ABC25 currently represents the most promising candidate associated with adult-plant resistance. Among the metabolites differentially accumulated in response to Prs, those related to phenylpropanoids, diterpenoids, and thiamine branches seem to play the most important role in the immune response. Finally, we suggest how the knowledge acquired so far about the rye-Prs interaction can be used in modern breeding programs aimed at obtaining cultivars with enhanced resistance to LR, such as through the use of functional gene markers and/or metabolic biomarker-assisted selection and, in the more distant future, by developing and applying new genomic techniques for precise editing of resistance and susceptibility genes, engineering synthetic immune receptors and decoys, and pan-genomic exploration for identification of rare or lineage-specific resistance alleles. [Formula: see text] Copyright © 2026 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Plant Diseases↗
PubMed2001

beta-cell apoptosis and defense mechanisms: lessons from type 1 diabetes.

Increased evidence suggests that apoptosis is the main mode of beta-cell death in early type 1 diabetes. Cytokines mediate beta-cell apoptosis, and in this article, we discuss some of the cytokine-modified genes that may contribute to beta-cell survival or death. The gene encoding for the inducible form of nitric oxide synthase is induced by interleukin (IL)-1beta or IL-1beta plus gamma-interferon in rodent and human islets, respectively. This leads to nitric oxide (NO) formation, which contributes to a major extent to beta-cell necrosis and to a minor extent to the process of beta-cell apoptosis. The main mode of cell death induced by cytokines in human beta-cells is apoptosis, whereas cytokines lead to both necrosis and apoptosis in rat and mouse beta-cells. It is suggested that the necrotic component in rodent islets is due to NO-induced mitochondrial impairment and consequent decreased ATP production. Human islets, possessing better antioxidant defenses, are able to preserve glucose oxidation and ATP production, and can thus complete the apoptotic program after the death signal delivered by cytokines. We propose that this death signal results from cytokine-induced parallel and/or sequential changes in the expression of multiple proapoptotic and prosurvival genes. The identity of these "gene modules" and of the transcription factors regulating them remains to be established.

Animals↗
PubMed2002

Oxidative stress, antioxidants and stress tolerance.

Traditionally, reactive oxygen intermediates (ROIs) were considered to be toxic by-products of aerobic metabolism, which were disposed of using antioxidants. However, in recent years, it has become apparent that plants actively produce ROIs as signaling molecules to control processes such as programmed cell death, abiotic stress responses, pathogen defense and systemic signaling. Recent advances including microarray studies and the development of mutants with altered ROI-scavenging mechanisms provide new insights into how the steady-state level of ROIs are controlled in cells. In addition, key steps of the signal transduction pathway that senses ROIs in plants have been identified. These raise several intriguing questions about the relationships between ROI signaling, ROI stress and the production and scavenging of ROIs in the different cellular compartments.

Adaptation, Physiological↗
PubMed1991

The dawn of Darwinian medicine.

While evolution by natural selection has long been a foundation for biomedical science, it has recently gained new power to explain many aspects of disease. This progress results largely from the disciplined application of what has been called the adaptations program. We show that this increasingly significant research paradigm can predict otherwise unsuspected facets of human biology, and that it provides new insights into the causes of medical disorders, such as those discussed below: 1. Infection. Signs and symptoms of the host-parasite contest can be categorized according to whether they represent adaptations or costs for host or parasite. Some host adaptations may have contributed to fitness in the Stone Age but are obsolete today. Others, such as fever and iron sequestration, have been incorrectly considered harmful. Pathogens, with their large populations and many generations in a single host, can evolve very rapidly. Acquisition of resistance to antibiotics is one example. Another is the recently demonstrated tendency to change virulence levels in predictable ways in response to changed conditions imposed incidentally by human activities. 2. Injuries and toxins. Mechanical injuries or stressful wear and tear are conceptually simpler than infectious diseases because they are not contests between conflicting interests. Plant-herbivore contests may often underlie chemical injury from the defensive secondary compounds of plant tissues. Nausea in pregnancy, and allergy, may be adaptations against such toxins. 3. Genetic factors. Common genetic diseases often result from genes maintained by other beneficial effects in historically normal environments. The diseases of aging are especially likely to be associated with early benefits. 4. Abnormal environments. Human biology is designed for Stone Age conditions. Modern environments may cause many diseases-for example, deficiency syndromes such as scurvy and rickets, the effects of excess consumption of normally scarce nutrients such as fat and salt, developmental diseases such as myopia, and psychological reactions to novel environments. The substantial benefits of evolutionary studies of disease will be realized only if they become central to medical curricula, an advance that may at first require the establishment of one or more research centers dedicated to the further development of Darwinian medicine.

Adaptation, Physiological↗
PubMed2003

[The structure and regulation of plant proteinase inhibitor genes and their strategy in pest control].

The diverse plant proteinase inhibitors (PIs) genes from different plant species have been isolated and their products with one or more genes are targeted at different biochemical and physiological process with the insect, and well played a potent defensive role against insects and pathogens. The use of recombinant PIs and synergistic activation to protect plants has been incorporated in integrated pest management program. Though they may not replace the use of chemical pesticides in the near future, but effectively complement it. Currently, the role and mechanism of action for most of these inhibitors are being studied in detail. This article describes the structure of PIs genes, their regulation and expression, and discusses the strategy to develop transgenic plants against phytophagous insects.

Animals↗
PubMed2004

Discovery, structure and biological activities of the cyclotides.

The cyclotides are a family of small disulfide rich proteins that have a cyclic peptide backbone and a cystine knot formed by three conserved disulfide bonds. The combination of these two structural motifs contributes to the exceptional chemical, thermal and enzymatic stability of the cyclotides, which retain bioactivity after boiling. They were initially discovered based on native medicine or screening studies associated with some of their various activities, which include uterotonic action, anti-HIV activity, neurotensin antagonism, and cytotoxicity. They are present in plants from the Rubiaceae, Violaceae and Cucurbitaceae families and their natural function in plants appears to be in host defense: they have potent activity against certain insect pests and they also have antimicrobial activity. There are currently around 50 published sequences of cyclotides and their rate of discovery has been increasing over recent years. Ultimately the family may comprise thousands of members. This article describes the background to the discovery of the cyclotides, their structural characterization, chemical synthesis, genetic origin, biological activities and potential applications in the pharmaceutical and agricultural industries. Their unique topological features make them interesting from a protein folding perspective. Because of their highly stable peptide framework they might make useful templates in drug design programs, and their insecticidal activity opens the possibility of applications in crop protection.

Animals↗
PubMed2002

Immunity, inflammation, and remodeling in the airway epithelial barrier: epithelial-viral-allergic paradigm.

The concept that airway inflammation leads to airway disease has led to a widening search for the types of cellular and molecular interactions responsible for linking the initial stimulus to the final abnormality in airway function. It has not yet been possible to integrate all of this information into a single model for the development of airway inflammation and remodeling, but a useful framework has been based on the behavior of the adaptive immune system. In that paradigm, an exaggeration of T-helper type 2 (Th2) over Th1 responses to allergic and nonallergic stimuli leads to airway inflammatory disease, especially asthma. In this review, we summarize alternative evidence that the innate immune system, typified by actions of airway epithelial cells and macrophages, may also be specially programmed for antiviral defense and abnormally programmed in inflammatory disease. Furthermore, this abnormality may be inducible by paramyxoviral infection and, in the proper genetic background, may persist indefinitely. Taken together, we propose a new model that highlights specific interactions between epithelial, viral, and allergic components and so better explains the basis for airway immunity, inflammation, and remodeling in response to viral infection and the development of long-term disease phenotypes typical of asthma and other hypersecretory airway diseases.

Animals↗
PubMed2003

Trace elements and host defense: recent advances and continuing challenges.

Although it is widely recognized that essential trace elements are required for the differentiation, activation and performance of numerous functions of immune cells, the specific roles of these inorganic micronutrients in these processes remain largely undefined. New insights about the participation of zinc, iron and copper in the selection, maturation and early activation events of the immune cells have been gained by judicious use of available tools in analytical cell biology, molecular genetics and array technology. Also, randomly controlled clinical and community trials demonstrate that zinc supplementation can enhance immunocompetence and decrease the incidence and severity of some infections in individuals with diagnosed or suspected mild zinc deficiency. These exciting results provide an impetus to evaluate the potential benefits of supplementation programs for individuals and groups with suboptimal trace element status as a cost-effective means of reducing the risk of infectious diseases.

Communicable Disease Control↗
PubMed1999

Oxidative stress in microorganisms--I. Microbial vs. higher cells--damage and defenses in relation to cell aging and death.

Oxidative stress in microbial cells shares many similarities with other cell types but it has its specific features which may differ in prokaryotic and eukaryotic cells. We survey here the properties and actions of primary sources of oxidative stress, the role of transition metals in oxidative stress and cell protective machinery of microbial cells, and compare them with analogous features of other cell types. Other features to be compared are the action of Reactive Oxygen Species (ROS) on cell constituents, secondary lipid- or protein-based radicals and other stress products. Repair of oxidative injury by microorganisms and proteolytic removal of irreparable cell constituents are briefly described. Oxidative damage of aerobically growing microbial cells by endogenously formed ROS mostly does not induce changes similar to the aging of multiplying mammalian cells. Rapid growth of bacteria and yeast prevents accumulation of impaired macromolecules which are repaired, diluted or eliminated. During growth some simple fungi, such as yeast or Podospora spp., exhibit aging whose primary cause seems to be fragmentation of the nucleolus or impairment of mitochondrial DNA integrity. Yeast cell aging seems to be accelerated by endogenous oxidative stress. Unlike most growing microbial cells, stationary-phase cells gradually lose their viability because of a continuous oxidative stress, in spite of an increased synthesis of antioxidant enzymes. Unlike in most microorganisms, in plant and animal cells a severe oxidative stress induces a specific programmed death pathway--apoptosis. The scant data on the microbial death mechanisms induced by oxidative stress indicate that in bacteria cell death can result from activation of autolytic enzymes (similarly to the programmed mother-cell death at the end of bacillary sporulation). Yeast and other simple eukaryotes contain components of a proapoptotic pathway which are silent under normal conditions but can be activated by oxidative stress or by manifestation of mammalian death genes, such as bak or bax. Other aspects, such as regulation of oxidative-stress response, role of defense enzymes and their control, acquisition of stress tolerance, stress signaling and its role in stress response, as well as cross-talk between different stress factors, will be the subject of a subsequent review.

Animals↗
PubMedDate not supplied

Medical preparedness against chemical and biological incidents for the NATO Summit in Istanbul and lessons learned.

INTRODUCTION: During the 2004 North Atlantic Treaty Organization (NATO) Summit, essential counter-measures, including medical preparedness, were taken to cope with any suspected terrorist case or events including the use of chemical or biological (CB) weapons. The Summit was held in Istanbul, a city that bridges two continents, and involved the participation of many Heads of State, Prime Ministers, and Defense Ministers from 26 NATO countries. METHODS: First responders, including medical Chemical, Biological, Radiological, and Nuclear (CBRN) teams, received special training. Essential equipment, including drugs, antidotes, detectors, etc., was provided and stock-piled. Medical authorities augmented the capacity for identifying and controlling the injuries and any emerging CB incident through the set-up of decontamination units and the procurement of medical devices, antidotes, drugs, and personal protective suits. Additionally, a small part of the recently established NATO-CBRN battalion was welcomed to the Summit and was prepared to perform detection and identification of the agent found in suspicious appearing samples. RESULTS: Although no CB incident was reported during the Summit, extensive experience was gained with respect to medical preparedness against CB terrorism. Sampling, detection, and analysis of toxic materials were taken into account in the medical management. Much laboratory-related work was conducted in the following time period. The laboratory work involved the standardization of sampling and transportation procedures, development of both mobile and reference laboratories, and performing research activities aimed to make the CB analysis more efficient. Although the training of the medical staff was advanced, training should be continuous and supported with educational programs, conferences, meetings, and tabletop and hospital medical exercises throughout the country. CONCLUSION: Multidisciplinary cooperation, training, and preparedness should be provided to basic medical care units and centers as part of the medical planning aimed at perfect detection and surveillance, laboratory analysis, and emergency response.

Bioterrorism↗
PubMed2005

NO way to live; the various roles of nitric oxide in plant-pathogen interactions.

Nitric oxide has attracted considerable interest from plant pathologists due its established role in regulating mammalian anti-microbial defences, particularly via programmed cell death (PCD). Although NO plays a major role in plant PCD elicited in response to certain types of pathogenic challenge, the race-specific hypersensitive response (HR), it is now evident that NO also acts in the regulation of non-specific, papilla-based resistance to penetration by plant cells that survive attack and, possibly, in systemic acquired resistance. Equally, the potential roles of NO signalling/scavenging within the pathogen are being recognized. This review will consider key defensive roles played by NO in living cells during plant-pathogen interactions, as well as in those undergoing PCD.

Amino Acid Sequence↗
PubMed2006

Involvement of PPAR nuclear receptors in tissue injury and wound repair.

Tissue damage resulting from chemical, mechanical, and biological injury, or from interrupted blood flow and reperfusion, is often life threatening. The subsequent tissue response involves an intricate series of events including inflammation, oxidative stress, immune cell recruitment, and cell survival, proliferation, migration, and differentiation. In addition, fibrotic repair characterized by myofibroblast transdifferentiation and the deposition of ECM proteins is activated. Failure to initiate, maintain, or stop this repair program has dramatic consequences, such as cell death and associated tissue necrosis or carcinogenesis. In this sense, inflammation and oxidative stress, which are beneficial defense processes, can become harmful if they do not resolve in time. This repair program is largely based on rapid and specific changes in gene expression controlled by transcription factors that sense injury. PPARs are such factors and are activated by lipid mediators produced after wounding. Here we highlight advances in our understanding of PPAR action during tissue repair and discuss the potential for these nuclear receptors as therapeutic targets for tissue injury.

Animals↗
PubMed2003

Gene expression profiling in porcine fetal thymus.

To obtain an initial overview of gene diversity and expression pattern in porcine thymus, 11,712 ESTs (Expressed Sequence Tags) from 100-day-old porcine thymus (FTY) were sequenced and 7,071 cleaned ESTs were used for gene expression analysis. Clustered by the PHRAP program, 959 contigs and 3,074 singlets were obtained. Blast search showed that 806 contigs and 1,669 singlets (totally 5,442 ESTs) had homologues in GenBank and 1,629 ESTs were novel. According to the Gene Ontology classification, 36.99% ESTs were cataloged into the gene expression group, indicating that although the functional gene (18.78% in defense group) of thymus is expressed in a certain degree, the 100-day-old porcine thymus still exists in a developmental stage. Comparative analysis showed that the gene expression pattern of the 100-day-old porcine thymus is similar to that of the human infant thymus.

Animals↗
PubMed1994

bcl-2 in cancer, development and apoptosis.

The bcl-2 gene provides a window on the basic cellular machinery of apoptosis or programmed cell death, a process involved in virtually all biologic events in multicellular organisms, but particularly relevant to neoplasia and development. bcl-2 gene function supports cell survival and appears to lie at a nodal point in pathways leading to activation or execution of apoptosis. Carcinogenesis may involve several steps at which cell death programs are normally activated and are bypassed in cancer cells, including apoptotic pathways activated by several oncogenes. Functional redundancy and the complexity of the regulation of cell survival are demonstrated by the less than expected phenotype of bcl-2 knockout mice and the cloning of several bcl-2 related genes, some of which promote cell death. The molecular function for bcl-2 is unknown, but several lines of evidence support a role in protection from oxidative stress. These studies suggest that many environmental perturbations and genetic pathways converge to disrupt a metabolic balance between oxidant generation and anti-oxidant defenses.

Amino Acid Sequence↗