Complex Defense Research Articles

Transcriptome Analysis of the Sydney Rock Oyster, Saccostrea glomerata: Insights into Molluscan Immunity

BackgroundOysters have important ecological functions in their natural environment, acting as global carbon sinks and improving water quality by removing excess nutrients from the water column. During their life-time oysters are exposed to a variety of pathogens that can cause severe mortality in a range of oyster species. Environmental stressors encountered in their habitat can increase the susceptibility of oysters to these pathogens and in general have been shown to impact on oyster immunity, making immune parameters expressed in these marine animals an important research topic.ResultsPaired-end Illumina high throughput sequencing of six S. glomerata tissues exposed to different environmental stressors resulted in a total of 484,121,702 paired-end reads. When reads and assembled transcripts were compared to the C. gigas genome, an overall low level of similarity at the nucleotide level, but a relatively high similarity at the protein level was observed. Examination of the tissue expression pattern showed that some transcripts coding for cathepsins, heat shock proteins and antioxidant proteins were exclusively expressed in the haemolymph of S. glomerata, suggesting a role in innate immunity. Furthermore, analysis of the S. glomerata ORFs showed a wide range of genes potentially involved in innate immunity, from pattern recognition receptors, components of the Toll-like signalling and apoptosis pathways to a complex antioxidant defence mechanism.ConclusionsThis is the first large scale RNA-Seq study carried out in S. glomerata, showing the complex network of innate immune components that exist in this species. The results confirmed that many of the innate immune system components observed in mammals are also conserved in oysters; however, some, such as the TLR adaptors MAL, TRIF and TRAM are either missing or have been modified significantly. The components identified in this study could help explain the oysters’ natural resilience against pathogenic microorganisms encountered in their natural environment.

The Defense Metabolite, Allyl Glucosinolate, Modulates Arabidopsis thaliana Biomass Dependent upon the Endogenous Glucosinolate Pathway.

Glucosinolates (GSLs) play an important role in plants as direct mediators of biotic and abiotic stress responses. Recent work is beginning to show that the GSLs can also inducing complex defense and growth networks. However, the physiological significance of these GSL-induced responses and the molecular mechanisms by which GSLs are sensed and/or modulate these responses are not understood. To identify these potential mechanisms within the plant and how they may relate to the endogenous GSLs, we tested the regulatory effect of exogenous allyl GSL application on growth and defense metabolism across sample of Arabidopsis thaliana accessions. We found that application of exogenous allyl GSL had the ability to initiate changes in plant biomass and accumulation of defense metabolites that genetically varied across accessions. This growth effect was related to the allyl GSL side-chain structure. Utilizing this natural variation and mutants in genes within the GSL pathway we could show that the link between allyl GSL and altered growth responses are dependent upon the function of known genes controlling the aliphatic GSL pathway.

An evolutionary argument for unconscious personal death unawareness

There is strong experimental evidence that reminders of personal death influence individuals’ attitudes and behaviours. However, there is less support for the typically underlying hypothesis of ‘death denial’, which holds that terror resulting from the awareness of personal mortality is addressed through a variety of psychological and cultural defences. This paper suggests it is evolutionarily more plausible that humans are unconsciously unaware of their own deaths, which would mitigate death-related anxiety without the need for costly and complex defences. While some aspects of the argument are necessarily speculative, problems with the death denial model, as well as relevant aspects of literature on consciousness and self-awareness, positive illusions and self-deception, support the possibility of unconscious death unawareness. The cognitive requirements of human calculated reciprocity also suggest a potentially adaptive function for personal death unawareness, as well as a maladaptive effect related to human tendencies to enter into reciprocal contracts involving afterlife rewards.

Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival.

Heat shock proteins (HSPs) belong to a superfamily of stress proteins that are critical constituents of a complex defense mechanism that enhances cell survival under adverse environmental conditions. Cell protective roles of HSPs are related to their chaperone functions, antiapoptotic and antinecrotic effects. HSPs' anti-apoptotic and cytoprotective characteristics, their ability to protect cells from a variety of stressful stimuli, and the possibility of their pharmacological induction in cells under pathological stress make these proteins an attractive therapeutic target for various neurodegenerative diseases; these include Alzheimer's, Parkinson's, Huntington's, prion disease, and others. This review discusses the possible roles of HSPs, particularly HSP70 and small HSPs (alpha A and alpha B crystallins) in enhancing the survival of retinal ganglion cells (RGCs) in optic neuropathies such as glaucoma, which is characterized by progressive loss of vision caused by degeneration of RGCs and their axons in the optic nerve. Studies in animal models of RGC degeneration induced by ocular hypertension, optic nerve crush and axotomy show that upregulation of HSP70 expression by hyperthermia, zinc, geranyl-geranyl acetone, 17-AAG (a HSP90 inhibitor), or through transfection of retinal cells with AAV2-HSP70 effectively supports the survival of injured RGCs. RGCs survival was also stimulated by overexpression of alpha A and alpha B crystallins. These findings provide support for translating the HSP70- and alpha crystallin-based cell survival strategy into therapy to protect and rescue injured RGCs from degeneration associated with glaucomatous and other optic neuropathies.

Activation of Shikimate, Phenylpropanoid, Oxylipins, and Auxin Pathways in Pectobacterium carotovorum Elicitors-Treated Moss.

Plants have developed complex defense mechanisms to cope with microbial pathogens. Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are perceived by pattern recognition receptors (PRRs), leading to the activation of defense. While substantial progress has been made in understanding the activation of plant defense by PAMPs and DAMPs recognition in tracheophytes, far less information exists on related processes in early divergent plants like mosses. The aim of this study was to identify genes that were induced in P. patens in response to elicitors of Pectobacterium carotovorum subsp. carotovorum, using a cDNA suppression subtractive hybridization (SSH) method. A total of 239 unigenes were identified, including genes involved in defense responses related to the shikimate, phenylpropanoid, and oxylipin pathways. The expression levels of selected genes related to these pathways were analyzed using quantitative RT-PCR, confirming their rapid induction by P.c. carotovorum derived elicitors. In addition, P. patens induced cell wall reinforcement after elicitor treatment by incorporation of phenolic compounds, callose deposition, and elevated expression of Dirigent-like encoding genes. Small molecule defense markers and phytohormones such as cinnamic acid, 12-oxo-phytodienoic acid, and auxin levels all increased in elicitor-treated moss tissues. In contrast, salicylic acid levels decreased while abscisic acid levels remained unchanged. P. patens reporter lines harboring an auxin-inducible promoter fused to β-glucuronidase revealed GUS activity in protonemal and gametophores tissues treated with elicitors of P.c. carotovorum, consistent with a localized activation of auxin signaling. These results indicate that P. patens activates the shikimate, phenylpropanoid, oxylipins, and auxin pathways upon treatment with P.c. carotovorum derived elicitors.

Transcriptomic and Proteomic Analysis of Arion vulgaris--Proteins for Probably Successful Survival Strategies?

The Spanish slug, Arion vulgaris, is considered one of the hundred most invasive species in Central Europe. The immense and very successful adaptation and spreading of A. vulgaris suggest that it developed highly effective mechanisms to deal with infections and natural predators. Current transcriptomic and proteomic studies on gastropods have been restricted mainly to marine and freshwater gastropods. No transcriptomic or proteomic study on A. vulgaris has been carried out so far, and in the current study, the first transcriptomic database from adult specimen of A. vulgaris is reported. To facilitate and enable proteomics in this non-model organism, a mRNA-derived protein database was constructed for protein identification. A gel-based proteomic approach was used to obtain the first generation of a comprehensive slug mantle proteome. A total of 2128 proteins were unambiguously identified; 48 proteins represent novel proteins with no significant homology in NCBI non-redundant database. Combined transcriptomic and proteomic analysis revealed an extensive repertoire of novel proteins with a role in innate immunity including many associated pattern recognition, effector proteins and cytokine-like proteins. The number and diversity in gene families encoding lectins point to a complex defense system, probably as a result of adaptation to a pathogen-rich environment. These results are providing a fundamental and important resource for subsequent studies on molluscs as well as for putative antimicrobial compounds for drug discovery and biomedical applications.

Neuroimmunity: Physiology and Pathology.

Evolution has yielded multiple complex and complementary mechanisms to detect environmental danger and protect tissues from damage. The nervous system rapidly processes information and coordinates complex defense behaviors, and the immune system eliminates diverse threats by virtue of mobile, specialized cell populations. The two systems are tightly integrated, cooperating in local and systemic reflexes that restore homeostasis in response to tissue injury and infection. They further share a broad common language of cytokines, growth factors, and neuropeptides that enables bidirectional communication. However, this reciprocal cross talk permits amplification of maladaptive feedforward inflammatory loops that contribute to the development of allergy, autoimmunity, itch, and pain. Appreciating the immune and nervous systems as a holistic, coordinated defense system provides both new insights into inflammation and exciting opportunities for managing acute and chronic inflammatory diseases.

Challenges of institutional coordination in complex defense acquisition programs: the case of the Republic of Korea’s F-X program

Decision-making in defense acquisition programs in the Republic of Korea (ROK) has been problematic, especially in highly advanced complex systems. The highly disputed force modernization program for the ROK Air Force’s fifth-generation fighter, dubbed the Fighter eXperiment, went through extreme turbulence during the type selection phase. The gist of the turbulence became evident through poor institutional coordination within the defense acquisition authorities that eventually forced them to rescind the decision generated from their own yearlong efforts, thus basically shooting themselves on the foot. The paper highlights the background of the program and reviews the institutional elements that influenced the decision-making process, and conclude that the absence of an effective coordination mechanism has made decision-making in complex defense programs even more troublesome.

Mitochondria as a Favourite Organelle for Invading Viruses

The self-destruction of cells infected with viruses undergoes the process of apoptosis generally to restrict infection and the spread of viral progeny. To avoid infection host has evolved interconnected complex defence network that comprises innate and acquired immune response. Mitochondria being considered as powerhouse of a cell is not limited to only energy production, but mitochondria perform various other functions in (disease, apoptosis and host innate immune system) which make them absolutely indispensable to the cell. This makes them a target of almost all the invading pathogens including viruses. Therefore being a multifunctional organelle, the viruses choose mitochondria as a favourite organelle as they can easily take control of the whole cell and make it to promote or block apoptosis as per their need.

How Trypanosoma cruzi deals with oxidative stress: Antioxidant defence and DNA repair pathways.

Trypanosoma cruzi, the causative agent of Chagas disease, is an obligatory intracellular parasite with a digenetic life cycle. Due to the variety of host environments, it faces several sources of oxidative stress. In addition to reactive oxygen species (ROS) produced by its own metabolism, T. cruzi must deal with high ROS levels generated as part of the host's immune responses. Hence, the conclusion that T. cruzi has limited ability to deal with ROS (based on the lack of a few enzymes involved with oxidative stress responses) seems somewhat paradoxical. Actually, to withstand such variable sources of oxidative stress, T. cruzi has developed complex defence mechanisms. This includes ROS detoxification pathways that are distinct from the ones in the mammalian host, DNA repair pathways and specialized polymerases, which not only protect its genome from the resulting oxidative damage but also contribute to the generation of genetic diversity within the parasite population. Recent studies on T. cruzi's DNA repair pathways as mismatch repair (MMR) and GO system suggested that, besides a role associated with DNA repair, some proteins of these pathways may also be involved in signalling oxidative damage. Recent data also suggested that an oxidative environment might be beneficial for parasite survival within the host cell as it contributes to iron mobilization from the host's intracellular storages. Besides contributing to the understanding of basic aspects of T. cruzi biology, these studies are highly relevant since oxidative stress pathways are part of the poorly understood mechanisms behind the mode of action of drugs currently used against this parasite. By unveiling new peculiar aspects of T. cruzi biology, emerging data on DNA repair pathways and other antioxidant defences from this parasite have revealed potential new targets for a much needed boost in drug development efforts towards a better treatment for Chagas disease.

Gut Microbiota Modulation and Mucosal Immunity: Focus on Rifaximin.

The gastrointestinal tract is a complex and dynamic network where an intricate and mutualistic symbiosis modulates the relationship between the host and the microbiota in order to establish and ensure gut homeostasis. Every day, thousands of compounds derived from food and microorganisms come in contact with the intestinal mucosa. This interaction requires a complex defense system that separates intestinal contents from the host tissues, regulates nutrient absorption, and allows tolerance between the resident bacterial flora and the mucosal immune system, while inhibiting translocation of infectious agents to the inner tissues. Unfavorable alteration of microbiota composition has been implicated in hepatic, gastrointestinal, and perhaps also systemic disorders. In this scenario, gut microbiota modulation represents an intriguing field and can be obtained by several approaches, including antibiotics, pro- and pre-biotics supplementation. Among antibiotics, Rifaximin seems to be a promising antibiotic to treat conditions related to gut microbiota imbalance and to potentially modulate intestinal homeostasis. This review focuses on what is currently known regarding the possible role of Rifaximin in restoring normal gut immune physiology and a healthy gut-liver axis. Detailed mechanistic studies will improve the development of targeted therapies that may shape gut microflora composition with the end goal of promoting gut health.

ALTERNATIVE MILITARY KEYNESIANISM AS A TOOL OF CIVIL-MILITARY COOPERATION IN THE FRAMEWORK OF THE EU DEFENCE POLICY

During the last year the security threats to the European Union have increased dramatically under the influence of military crisis in eastern Ukraine and Islamic terrorist activities in Europe. Consequently the demand for defence in the member states of the European Union has become greater than in previous years. This situation leads to the dilemma when the high level of defence expenditure can hamper the financial support of other sectors of national economy. Therefore it is necessary to increase the efficiency of available financial resources that have been allocated for the defence without a significant increase in defence expenditure. In order to achieve this efficiency the concept of closer cooperation between military and civil sector can be the base for complex defence support measures that use the potential of national economy.DOI: http://dx.doi.org/10.5755/j01. eis.0.9.12793

A novel role of Drosophila cytochrome P450-4e3 in permethrin insecticide tolerance

The exposure of insects to xenobiotics, such as insecticides, triggers a complex defence response necessary for survival. This response includes the induction of genes that encode key Cytochrome P450 monooxygenase detoxification enzymes. Drosophila melanogaster Malpighian (renal) tubules are critical organs in the detoxification and elimination of these foreign compounds, so the tubule response induced by dietary exposure to the insecticide permethrin was examined. We found that expression of the gene encoding Cytochrome P450-4e3 (Cyp4e3) is significantly up-regulated by Drosophila fed on permethrin and that manipulation of Cyp4e3 levels, specifically in the principal cells of the Malpighian tubules, impacts significantly on the survival of permethrin-fed flies. Both dietary exposure to permethrin and Cyp4e3 knockdown cause a significant elevation of oxidative stress-associated markers in the tubules, including H2O2 and lipid peroxidation byproduct, HNE (4-hydroxynonenal). Thus, Cyp4e3 may play an important role in regulating H2O2 levels in the endoplasmic reticulum (ER) where it resides, and its absence triggers a JAK/STAT and NF-κB-mediated stress response, similar to that observed in cells under ER stress. This work increases our understanding of the molecular mechanisms of insecticide detoxification and provides further evidence of the oxidative stress responses induced by permethrin metabolism.

Antioxidantes en la mujer climatérica Oxidación – Antioxidación

Para los organismos aerobios es imprescindible la utilización del oxígeno del aire. Sin embargo, también se sabe que alrededor de 2 a 5% de ese oxígeno se reduce, formando radicales libres (EROs) -como el anión superóxido, el radical hidroxilo y la molécula de peróxido de hidrógeno-, además de radicales orgánicos producidos por las reacciones de propagación; estas pueden dañar a las biomoléculas celulares, iniciando en la mejor de las situaciones el proceso de apoptosis y, en otros casos, la necrosis. Como parte de la evolución y de nuestra adaptación a la toxicidad de este gas hemos desarrollado un complejo sistema de defensa antioxidante con componentes endógenos (superóxido dismutasa-SOD, catalasa, glutatión peroxidasa, glutatión, ácido úrico, bilirrubina, ácido lipoico) y exógenos (vitaminas A, C y E, además de polifenoles), que son incluidos en nuestra dieta cotidiana. Esta paradoja del oxígeno durante toda la vida conduce a un estado de estrés oxidativo y contribuye al proceso de senescencia que, sin embargo, no es homogéneo para todos nuestros sistemas corporales. En la vida del ser humano, el sistema reproductor femenino es uno de los que envejecen a mayor velocidad; una de las características de esta etapa es la disminución de la producción de estrógenos que, adicional a su clásica función hormonal, también ha demostrado tener capacidad antioxidante directa, así como participar como activador de señales intracelulares para la homeostasis redox.

Rethinking contract design: Why incorporating non-legal drivers of contractual behavior in contracts may lead to better results in complex defense systems procurement

Defense acquisition programs are plagued by surging delays and cost overruns. In particular, contract management of defense acquisition programs has been identified as 'high risk' - and threatening to project results. This article examines how contracts, as legal mechanisms, may be disruptive and obstruct cooperation between the DoD and contractors. The main observation this article makes is that tensions between the norms set forth in contracts and other non-legal norms can become a major reason for problems in defense procurement. It explains why these tensions may undermine cooperative behavior between contractors and the DoD and can become a source of disappointing acquisition program results. A framework is provided for identifying such tensions, and contract design principles are proposed to enhance cooperation and eliminate these tensions when drafting contracts for defense acquisition and other complex programs.

Analysis Method based on Rough Attack-defense Bayes Game Model

In order to solve the strategic interdependence question during the attack and defense process in a complex network, the dissertation proposes an analysis method based on rough attack-defense Bayes game model. After defining the inner structure of attacking agent and defense agent, the dissertation extends traditional object Petri Net and introduces rough set theory into node domain and transition domain, then propose the network attack-defense confrontation model. By dividing domain attack strategy set into equivalence classes, the extraction method of characteristic attack strategy set is given. Then the rough game model and utility function of attack and defense agents are defined, accordingly, the solution of Bayes equilibrium strategy and maximal attack and defense strategy set are proposed. The analysis method can reduce the scale of strategic space of the game model, and suitable for researching on complex network attack and defense action.

Expression profiles of sugarcane under drought conditions: Variation in gene regulation.

Drought is a major factor in decreased sugarcane productivity because of the resulting morphophysiological effects that it causes. Gene expression studies that have examined the influence of water stress in sugarcane have yielded divergent results, indicating the absence of a fixed pattern of changes in gene expression. In this work, we investigated the expression profiles of 12 genes in the leaves of a drought-tolerant genotype (RB72910) of sugarcane and compared the results with those of other studies. The genotype was subjected to 80–100% water availability (control condition) and 0–20% water availability (simulated drought). To analyze the physiological status, the SPAD index, Fv/Fm ratio, net photosynthesis (A), stomatal conductance (g s) and stomatal transpiration (E) were measured. Total RNA was extracted from leaves and the expression of SAMDC, ZmPIP2-1 protein, ZmTIP4-2 protein, WIP protein, LTP protein, histone H3, DNAj, ferredoxin I, β-tubulin, photosystem I, gene 1 and gene 2 was analyzed by quantitative real-time PCR (RT-PCR). Important differences in the expression profiles of these genes were observed when compared with other genotypes, suggesting that complex defense mechanisms are activated in response to water stress. However, there was no recognizable pattern for the changes in expression of the different proteins associated with tolerance to drought stress.

Mechanics of the ptychoid defense mechanism in Ptyctima (Acari, Oribatida): One problem, two solutions

The most complex mechanical defense of oribatid mites is ptychoidy, in which the animals can retract their legs and gnathosoma into the idiosoma and encapsulate by deflecting the prodorsum. Since Acari lack most antagonistic musculature, extension of appendages is facilitated through hemolymph pressure that in mites mostly is generated by dorso-ventral compression of the opisthosoma. The hardened notogaster of box mites requires a different system of pressure generation that is also able to accommodate huge hemolymph movement accompanying ptychoidy. We compared the functional morphology of ptychoidy in one model species from each of the two ptyctime superfamilies, Euphthiracaroidea and Phthiracaroidea, using synchrotron X-ray microtomography and high-speed videography. We show that the two groups evolved very different functional modes of hydrostatic pressure control. While euphthiracaroids employ a lateral compression of the notogaster using all muscles of the opisthosomal compressor system, phthiracaroids employ a dorsoventral compression generated by only the notogaster lateral compressor and additionally the postanal muscle; these retract the temporarily unified ventral plates into the idiosoma, revealing the poam as an integral part of the opisthosomal compressor system in this group. The primitive mode of operation for generating hemolymph pressure in the Ptyctima probably was lateral compression, as molecular studies indicate that Phthiracaroidea evolved within Euphthiracaroidea. In this hypothesis, dorsoventral compression evolved secondarily in phthiracaroid mites, but whether the immediate ancestors of Ptyctima used lateral or dorsoventral compression remains to be determined.

Proteomics-Level Identification of Degradation-Resistant Proteins Provide Insight about their Potential Roles in Organismal Adaptation to Stress

Some proteins are hyperstable, as demonstrated by their resistance to proteolysis and detergents, and their long half-life. Some of these proteins are characterized by having a high energy barrier toward unfolding that virtually traps them in their native state. This property of proteins, known as “kinetic stability” (KS), appears to be a strategy used by “mother nature” to protect certain proteins against aggregation, and premature degradation under stress conditions. In addition to saving organismal resources by avoiding frequent degradation-biosynthesis of proteins, KSPs could function under extreme stress to maintain vital functions needed for survival. On the basis of our observed correlation between KS and a protein's resistance to the detergent SDS, we developed a diagonal two-dimensional (D2D) SDS-PAGE method for the proteome-level identification of KSPs. We applied D2D SDS-PAGE to the lysate of Thermus thermophilus and E. coli followed by proteomics analysis, and identified over 100 KSPs. We also analyzed the cell lysates of various prokaryotic and eukaryotic organisms. Our results suggest that KS was likely a critically important property of proteins for the adaptation and survival of microbial organisms under stress conditions. In contrast, the minimal abundance of KSPs in eukaryotic organisms implies an evolutionary compromise of KS in favor of more complex cellular defense, function, and regulation. Thus, D2D SDS-PAGE is a simple and powerful method that may be applied to any complex mixture of proteins to explore the biological and pathological significance of protein kinetic stability.

The role of nutritional lipids and antioxidants in UV-induced skin cancer.

Two dietary tenets of the free radical theory of cancer require refinement. The first was dietary reduction of vulnerable free-radical targets, e.g., polyunsaturated lipids. The second was the addition of one or more antioxidants to the diet. Further, it was reported in 1939 that high levels of dietary fat exacerbated UV-carcinogenesis. Both lines of enquiry (dietary lipid and antioxidant effects on UV-carcinogenesis) were investigated. Both dietary lipids and antioxidants modified carcinogenic expression. Increasing levels of omega-6 polyunsaturated fatty acids (PUFA) exacerbated UV-carcinogenesis. However, omega-3 PUFA dramatically inhibited carcinogenic expression. It is probable that the action of omega-6 and-3 PUFA rests with differential metabolic intermediates, both tumor promoting and immune-modulating, that each PUFA generates through lipoxygenase and cyclooxygenase pathways. Antioxidant supplementation with butylated hydroxytoluene or beta-carotene demonstrated that each exerted its own specific antioxidant mechanism(s). When introduced into the complex milieu of the cell with its own intricate and complex antioxidant defense system, detrimental effects may ensue. These results point to oversimplification of these dietary suggestions to reduce cancer risk and the necessity to refine these dietary recommendations.