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Results for “Biological Defense Research Program”

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PubMed2000

Thiol homeostasis and supplements in physical exercise.

Thiols are a class of organic sulfur derivatives (mercaptans) characterized by the presence of sulfhydryl residues. In biological systems, thiols have numerous functions, including a central role in coordinating the antioxidant defense network. Physical exercise may induce oxidative stress. In humans, a consistent marker of exercise-induced oxidative stress is blood glutathione oxidation. Physical training programs have specific effects on tissue glutathione metabolism that depend on the work program and the type of tissue. Experimental studies show that glutathione metabolism in several tissues sensitively responds to an exhaustive bout of exercise. Study of glutathione-deficient animals clearly indicates the central importance of having adequate tissue glutathione to protect against exercise-induced oxidative stress. Among the various thiol supplements studied, N-acetyl-L-cysteine and alpha-lipoic acid hold the most promise. These agents may have antioxidant effects at the biochemical level but are also known to influence redox-sensitive cell signaling.

Acetylcysteine↗

PubMed2005

POCO: discovery of regulatory patterns from promoters of oppositely expressed gene sets.

Functionally associated genes tend to be co-expressed, which indicates that they could also be co-regulated. Since co-regulation is usually governed by transcription factors via their specific binding elements, putative regulators can be identified from promoter sets of (co-expressed) genes by screening for over-represented nucleotide patterns. Here, we present a program, POCO, which discovers such over-represented patterns from either one or two promoter sets. Typical microarray experiments yield up- and down-regulated gene sets that may represent, for example, distinct defense pathways. Assuming that a functional transcription factor cannot simultaneously both up- and down-regulate the gene sets, its binding element should respectively be over- and under-represented in the corresponding promoter sets. This idea is implemented in POCO, which tests the hypothesis that the distributions of a pattern differ among three sets of promoters: up-regulated, down-regulated and randomly-chosen. In the program, pattern discovery is based on explicit enumeration of all possible patterns on the alphabet (A, C, G, T and N). The mean occurrences and SDs of the patterns are estimated using bootstrapping and their significance is assessed using ANOVA F-statistics, Tukey's honestly significantly difference test and P-values. The program is freely available at http://ekhidna.biocenter.helsinki.fi/poco.

Binding Sites↗

PubMed2005

Increase in toxicity of an invasive weed after reassociation with its coevolved herbivore.

The ability of weeds to proliferate into nonindigenous habitats has been attributed to escape from their native natural enemies, allowing reallocation of resources from chemical defense into growth and reproduction. Many invasive weeds, however, eventually encounter their native, coevolved enemies in areas of introduction. Examination of herbarium specimens of an invasive phototoxic European weed, Pastinaca sativa, through 152 years reveals phytochemical shifts coincident in time with the accidental introduction of a major herbivore, the parsnip webworm, Depressaria pastinacella. Plants collected before the introduction of webworms in North America and during the earliest stages of establishment (1850-1889) are lower in toxic furanocoumarins than all plants subsequently collected in North America and lower than European plant samples collected before 1889. Thus, introduction of a major specialist herbivore can increase noxiousness of a species in its area of introduction, illuminating a potential consequence of classical biocontrol programs involving insect herbivores and poisonous weeds.

Animals↗

PubMed2004

System-based proteomic analysis of the interferon response in human liver cells.

BACKGROUND: Interferons (IFNs) play a critical role in the host antiviral defense and are an essential component of current therapies against hepatitis C virus (HCV), a major cause of liver disease worldwide. To examine liver-specific responses to IFN and begin to elucidate the mechanisms of IFN inhibition of virus replication, we performed a global quantitative proteomic analysis in a human hepatoma cell line (Huh7) in the presence and absence of IFN treatment using the isotope-coded affinity tag (ICAT) method and tandem mass spectrometry (MS/MS). RESULTS: In three subcellular fractions from the Huh7 cells treated with IFN (400 IU/ml, 16 h) or mock-treated, we identified more than 1,364 proteins at a threshold that corresponds to less than 5% false-positive error rate. Among these, 54 were induced by IFN and 24 were repressed by more than two-fold, respectively. These IFN-regulated proteins represented multiple cellular functions including antiviral defense, immune response, cell metabolism, signal transduction, cell growth and cellular organization. To analyze this proteomics dataset, we utilized several systems-biology data-mining tools, including Gene Ontology via the GoMiner program and the Cytoscape bioinformatics platform. CONCLUSIONS: Integration of the quantitative proteomics with global protein interaction data using the Cytoscape platform led to the identification of several novel and liver-specific key regulatory components of the IFN response, which may be important in regulating the interplay between HCV, interferon and the host response to virus infection.

Cell Line, Tumor↗

PubMed1998

Mycobacterial pathogenesis: a historical perspective.

Tuberculosis is an age-old human affliction which continues to flourish worldwide despite the development of effective drugs for its treatment and a vaccine (BCG) for its prevention. At least 8 million people die from this disease each year, a figure which is likely to increase as the AIDS epidemic continues its relentless spread into Africa and Southeast Asia. Consumption was shown to be caused by Mycobacterium tuberculosis more than a century ago, yet we still know very little about the mechanisms used by this organism to elude the normally effective cellular host defenses as it establishes a progressive infection within the lung. The majority of individuals exposed to tuberculous infection are able to limit the primary infection to the lungs and its lymph nodes, resulting in a latent form of the disease which can provide the host with a lifelong immunity to reinfection. While a great deal is known about the cellular mediators of this immune response (together with the cytokines which modulate them) we lack a clear understanding of the role that they play during the establishment of the dormant form of the disease. Live BCG vaccine has been widely used in many Third World countries as a major component of their tuberculosis control programs. However, several carefully controlled human trials have shown little protection achieved in vaccinated individuals. Development of improved vaccines, both for the prevention and therapy of this disease is an urgent research priority and a number of potential immunogens are under active investigation. However, our limited understanding of the pathogenesis of this chronic disease, together with a lack of data on the role played by different bacterial components in the modulation of the immune response, continues to severely limit our ability to develop a rational approach to this project. To achieve this goal, it will be necessary to establish innovative approaches to the presentation of protective antigens by taking advantage of recent advances in the molecular biology of this complex and enigmatic group of organisms.

Animals↗

PubMed2006

Evolutionary neural networks for anomaly detection based on the behavior of a program.

The process of learning the behavior of a given program by using machine-learning techniques (based on system-call audit data) is effective to detect intrusions. Rule learning, neural networks, statistics, and hidden Markov models (HMMs) are some of the kinds of representative methods for intrusion detection. Among them, neural networks are known for good performance in learning system-call sequences. In order to apply this knowledge to real-world problems successfully, it is important to determine the structures and weights of these call sequences. However, finding the appropriate structures requires very long time periods because there are no suitable analytical solutions. In this paper, a novel intrusion-detection technique based on evolutionary neural networks (ENNs) is proposed. One advantage of using ENNs is that it takes less time to obtain superior neural networks than when using conventional approaches. This is because they discover the structures and weights of the neural networks simultaneously. Experimental results with the 1999 Defense Advanced Research Projects Agency (DARPA) Intrusion Detection Evaluation (IDEVAL) data confirm that ENNs are promising tools for intrusion detection.

Algorithms↗

PubMed2006

Streptococcus pneumoniae: the role of apoptosis in host defense and pathogenesis.

Programmed cell death or apoptosis is a recognised feature of infection with Streptococcus pneumoniae, and is observed during pneumococcal meningitis and pneumonia. The cholesterol-dependent cytolysin, pneumolysin, is a major trigger of apoptosis in the brain in association with pneumococcal production of hydrogen peroxide. Pneumococcal cell wall is also an important stimulus for apoptosis. Microbial factors and host factors combine in causing apoptosis in the brain, with hippocampal neurons being particularly susceptible. In pulmonary infection epithelial cell apoptosis contributes to tissue injury but macrophage apoptosis may benefit the host, aiding microbial killing and downregulating the inflammatory response. During sepsis lymphocyte apoptosis may be harmful to the host while dendritic cell apoptosis may limit the generation of an adaptive immune response during infection. Apoptosis induction may be harmful or potentially beneficial during pneumococcal infection and understanding its function in each setting is essential to allow specific therapeutic intervention.

Animals↗

PubMed1990

Oxidative stress as a causal factor in differentiation and aging: a unifying hypothesis.

In this article, the authors have pointed out flaws in the current version of the free radical hypothesis of aging and have advanced a new hypothesis that reconciles and encapsulates existing information. The main premise of this hypothesis is that aging is a continuation of development and is thus influenced by genetically programmed phenomena. Completion of various genetic programs and the duration of life are linked to a metabolic potential which is itself a genetically determined sum of energy expenditure. Nevertheless, the rate at which metabolic potential is reached is linked to the rate of metabolism and the level of oxidative stress both of which are influenced by epigenetic stimuli. The current version of the free radical hypothesis postulates that partially reduced oxygen species are produced in aerobic cells in an uncontrolled fashion and do not play any useful physiological function. The principle tenet of the free radical hypothesis is that molecular damage is the underlying cause of aging and that O2- radicals and derivatives induce most of the damage sustained by cells during aging. The authors regard this hypothesis as flawed because it fails to explain either low randomly occurring damage can lead to age-associated changes that are species-specific, or the sequential nature of the changes that occur in aging organisms. In contrast to the free radical hypothesis, our hypothesis can explain the specific and sequential nature of aging-related changes because they are postulated to be neither dependent upon uncontrolled damage nor the cellular capacity to prevent it. Instead, the authors suggest that the damage accumulated during aging is a secondary effect rather than a direct cause of senescence. The authors have shown that cells exert control not only on their level of antioxidant defense but also on their rate of oxidant production. The authors postulate that aging is the terminal stage of development, and as such is influenced genetically. The authors also postulate that a definite sum of energy is required to complete the genetic programs associated with aging. Thus, the rate of aging is linked to the level of oxidative stress; the rate of energy utilization is postulated to determine the level of oxidative stress. Oxidative stress is one of the factors which appears to govern changes in gene expression during differentiation and we suggest that it causes alterations in gene expression during aging. In the authors revised hypothesis, free radicals promote aging by affecting specific genetic programs and the incidental damage they inflict in cells is only a by-product of this process.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed2006

Bacterial lipopolysaccharides induce defense responses associated with programmed cell death in rice cells.

PAMP (pathogen-associated molecular pattern) recognition plays an important role during the innate immune response in both plants and animals. Lipopolysaccharides (LPS) derived from Gram-negative bacteria are representative of typical PAMP molecules and have been reported to induce defense-related responses, including the suppression of the hypersensitive response, the expression of defense genes and systemic resistance in plants. However, the details regarding the precise molecular mechanisms underlying these cellular responses, such as the molecular machinery involved in the perception and transduction of LPS molecules, remain largely unknown. Furthermore, the biological activities of LPS on plants have so far been reported only in dicots and no information is thus available regarding their functions in monocots. In our current study, we report that LPS preparations for various becteria, including plant pathogens and non-pathogens, can induce defense responses in rice cells, including reactive oxygen generation and defense gene expression. In addition, global analysis of gene expression induced by two PAMPs, LPS and chitin oligosaccharide, also reveals a close correlation between the gene responses induced by these factors. This indicates that there is a convergence of signaling cascades downstream of their corresponding receptors. Furthermore, we show that the defense responses induced by LPS in the rice cells are associated with programmed cell death (PCD), which is a finding that has not been previously reported for the functional role of these molecules in plant cells. Interestingly, PCD induction by the LPS was not detected in cultured Arabidopsis thaliana cells.

Adsorption↗

PubMed2004

Acaricidal properties of a Chenopodium-based botanical.

The emulsifiable concentrate UDA-245 [25% EC (vol:vol)], based on an essential oil extract from Chenopodium ambrosioides variety ambrosioides, a North American herbaceous plant, was compared with commercially available pesticides for their effectiveness to control the adult stage and egg hatch of the twospotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae) and the European red mite, Panonychus ulmi (Koch) (Acari: Tetranychidae). After a laboratory bioassay with adult twospotted spider mites, a 0.5% concentration of UDA-245 was more effective than 0.7% (AI) of neem oil (Neem Rose Defense). After a similar bioassay with the European red mite, a 0.5% concentration UDA-245 was as effective as 0.006% (AI) of abamectin (Avid). UDA-245 at 0.5% significantly reduced egg hatch of the twospotted spider mite, 5 and 9 d after treatment and of the European red mite 6 d after treatment. Egg hatch was significantly lower using 0.006% (AI) of abamectin, 0.7% of neem oil, and 1.0% insecticidal soap than UDA-245. Residual tests indicated that UDA-245 may be persistent in the environment only for a few hours. Only 23% mortality was noted when mites were introduced on bean leaves 1 h after treatment with a 2% concentration of UDA-245. At the recommended dose of 0.5%, UDA-245 was not considered phytotoxic for most plants tested, i.e., lettuce, roses, and tomatoes. Results suggest that a greenhouse integrated pest management program using UDA-245 could effectively and selectively control mite infestations by treating "hot spots" with negligible effect on biological control agents when treating before introduction or when natural enemies are absent.

Acari↗

PubMed2006

Reconstruction of external dose from beta radiation sources of nuclear weapon origin.

In response to requests from the Department of Veterans Affairs, a methodology was developed to assess the external dose accrued by personnel in the vicinity of beta radiation sources of nuclear weapon origin. This methodology has been applied in support of the Nuclear Test Personnel Review (NTPR) Program implemented by the Department of Defense. As required by the Code of Federal Regulations (Title 32, Part 218 and Title 38, Part 3.311), the NTPR Program must evaluate radiological hazards from nuclear testing activities that include alpha particle, beta particle, neutron, and photon emissions from radionuclides. Prior to the development of this methodology, only photon and neutron radiations were explicitly quantified for external dose assessments in this program. Alpha radiation of external origin presents no risk for biological effects due to external dose potential to skin tissue because of the particle's very limited range. However, beta particles are sufficiently penetrating to have such potential. Methods are provided to quantify ionizing radiation doses to the skin and lens of the eye from beta radiation sources of nuclear weapon origin located external to the body. This formulation allows the estimation of beta dose from a film badge (gamma) dose or from an equivalent reconstructed gamma dose.

Algorithms↗

PubMed2001

The NOD: a signaling module that regulates apoptosis and host defense against pathogens.

Nods, a growing family of proteins containing a nucleotide-binding oligomerization domain (NOD), are involved in the regulation of programmed cell death (PCD) and immune responses. Members of the family include Apaf-1, Ced-4, Nod1, Nod2, and the cytosolic products of plant disease resistance genes. The NOD module is homologous to the ATP-binding cassette (ABC) found in a large number of proteins with diverse biological function. The centrally located NOD promotes activation of effector molecules through self-association and induced proximity of binding partners. The C-terminal domain of Nods serves as a sensor for intracellular ligands, whereas the N-terminal domain mediates binding to dowstream effector molecules and activation of diverse signaling pathways. Thus, Nods activate, through the NOD module, diverse signaling pathways involved in the elimination of cells via PCD and the host defense against pathogens.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Oxidation-sensitive mechanisms, vascular apoptosis and atherosclerosis.

Increased generation of oxidants, resulting from disruption of aerobic metabolism and from respiratory burst, is an essential defense mechanism against pathogens and aberrant cells. However, oxidative stress can also trigger and enhance deregulated apoptosis or programmed cell death, characteristic of atherosclerotic lesions. Oxidation-sensitive mechanisms also modulate cellular signaling pathways that regulate vascular expression of cytokines and growth factors, and influence atherogenesis, in particular when increased levels of plasma lipoproteins provide ample substrate for lipid peroxidation and lead to increased formation of adducts with lipoprotein amino acids. In some cases, increased oxidation and apoptosis in a group of cells might be beneficial for survival and function of other groups of arterial cells. However, overall, oxidation and apoptosis appear to promote the progression of diseased arteries towards a lesion that is vulnerable to rupture, and to give rise to myocardial infarction and ischemic stroke. Recent rapid advances in our understanding of the interactions between oxidative stress, apoptosis and arterial gene regulation suggest that selective interventions targeting these biological functions have great therapeutic potential.

Apoptosis↗

PubMed2005

Automated screening for biological weapons in homeland defense.

Biological threat detection programs that collect air samples and monitor for large-scale release of biowarfare agents generate large numbers of samples that must be quickly and accurately screened for the presence of biological agents. An impediment to the rapid analysis of large numbers of environmental biological samples is that manual laboratory processes are time-consuming and require resources to maintain infrastructure, trained personnel, and adequate supplies of testing reagents. An ideal screening system would be capable of processing multiple samples rapidly, cost-effectively, and with minimal personnel. In the present study, we evaluated the Automated Biological Agent Testing System (ABATS) to explore the capability of automation to increase sample throughput, maximize system accuracy, and reduce the analysis costs associated with biological threat agent screening in environmental samples. This study demonstrates the utility of this concept and the potential of an automated system to address the growing environmental monitoring needs of the United States.

Automation↗

PubMed2005

Mitochondrial apoptotic pathways.

Apoptosis or programmed cell death (PCD) is a physiological process characteristic of pluricellular organisms leading to self-destruction of the cell. It is therefore involved in development, homeostasis and host defense. However, a significant difference has been shown between mammalian cell apoptosis and non-mammalian cell apoptosis: mitochondria are implicated only in the former. Execution of PCD includes the release of several proapoptotic proteins from the intermembrane space of mitochondria. They could exert their actions through a caspase dependent as well as a caspase independent way. On the other hand, regulation of PCD is mainly given by the Bcl-2 family members, which are in turn essentially regulated by activation of death receptors and/or DNA damage. Nowadays, execution of apoptosis is better known than its regulation. Nevertheless, we are still far of a complete understanding of the apoptotic process.

Animals↗

PubMed2002

Yeast as a model to study apoptosis?

Programmed cell death (PCD) serves as a major mechanism for the precise regulation of cell numbers, and as a defense mechanism to remove unwanted and potentially dangerous cells. Despite the striking heterogeneity of cell death induction pathways, the execution of the death program is often associated with characteristic morphological and biochemical changes termed apoptosis. Although for a long time the absence of mitochondrial changes was considered as a hallmark of apoptosis, mitochondria appear today as the central executioner of programmed cell death. This crucial position of mitochondria in programmed cell death control is not due to a simple loss of function (deficit in energy supplying), but rather to an active process in the regulation of effector mechanisms. The large diversity of regulators of apoptosis in mammals and their numerous interactions complicate the analysis of their individual functions. Yeast, eukaryotic but unicellular organism, lack the main regulators of apoptosis (caspases, Bcl-2 family members, ...) found in mammals. This absence render them a powerful tool for heterologous expression, functional studies, and even cloning of new regulators of apoptosis. Great advances have thus been made in our understanding of the molecular mechanisms of Bcl-2 family members interactions with themselves and other cellular proteins, specially thanks to the two hybrid system and the easy manipulation of yeast (molecular biology and genetics). This review will focus on the use of yeast as a tool to identify new regulators and study function of mammalian apoptosis regulators.

Apoptosis↗

PubMed2005

Modeling human behaviors and reactions under dangerous environment.

This paper describes the framework of a real-time simulation system to model human behavior and reactions in dangerous environments. The system utilizes the latest 3D computer animation techniques, combined with artificial intelligence, robotics and psychology, to model human behavior, reactions and decision making under expected/unexpected dangers in real-time in virtual environments. The development of the system includes: classification on the conscious/subconscious behaviors and reactions of different people; capturing different motion postures by the Eagle Digital System; establishing 3D character animation models; establishing 3D models for the scene; planning the scenario and the contents; and programming within Virtools Dev. Programming within Virtools Dev is subdivided into modeling dangerous events, modeling character's perceptions, modeling character's decision making, modeling character's movements, modeling character's interaction with environment and setting up the virtual cameras. The real-time simulation of human reactions in hazardous environments is invaluable in military defense, fire escape, rescue operation planning, traffic safety studies, and safety planning in chemical factories, the design of buildings, airplanes, ships and trains. Currently, human motion modeling can be realized through established technology, whereas to integrate perception and intelligence into virtual human's motion is still a huge undertaking. The challenges here are the synchronization of motion and intelligence, the accurate modeling of human's vision, smell, touch and hearing, the diversity and effects of emotion and personality in decision making. There are three types of software platforms which could be employed to realize the motion and intelligence within one system, and their advantages and disadvantages are discussed.

Artificial Intelligence↗

PubMed1997

A molecular genetic approach to improved animal health. The effect of interferon genotype on the severity of experimental bovine herpesvirus-1 infection.

In the past decade, biotechnology has brought veterinary medicine an increased understanding of the effects of genetic background on disease resistance and production traits. Specific point mutations have been identified for a number of genetic diseases and genetic testing; selective breeding programs can eliminate these diseases from the population. Complex traits such as disease resistance and production traits are thought to be under the control of multiple genes, making their manipulation more difficult. Because of their antiviral and immune modulating properties, interferons may be a role in the host defense against viral infection. The Type I interferon gene family has been detailed in cattle and consists of approximately 32 genes clustered together on bovine chromosome 8. These genes are very polymorphic in the population, enabling studies on the association between alleles at specific interferon loci and the severity of clinical diseases following experimental Bovine Herpesvirus-1 infection. Associations were observed between specific IFN genotypes and increased severity of clinical disease in a population of unrelated cattle. With a better understanding of IFNs at the genetic level, it may eventually be possible to manipulate the IFN response for the therapeutic benefit of cattle, and lessen the economic impact of specific diseases on cattle producers.

Alleles↗