Multilevel Defense Research Articles

Retention of the RNA ends provides the molecular memory for maintaining the activation of the Csm complex.

The type III CRISPR-Cas effector complex Csm functions as a molecular Swiss army knife that provides multilevel defense against foreign nucleic acids. The coordinated action of three catalytic activities of the Csm complex enables simultaneous degradation of the invader's RNA transcripts, destruction of the template DNA and synthesis of signaling molecules (cyclic oligoadenylates cAn) that activate auxiliary proteins to reinforce CRISPR-Cas defense. Here, we employed single-molecule techniques to connect the kinetics of RNA binding, dissociation, and DNA hydrolysis by the Csm complex from Streptococcus thermophilus. Although single-stranded RNA is cleaved rapidly (within seconds), dual-color FCS experiments and single-molecule TIRF microscopy revealed that Csm remains bound to terminal RNA cleavage products with a half-life of over 1 hour while releasing the internal RNA fragments quickly. Using a continuous fluorescent DNA degradation assay, we observed that RNA-regulated single-stranded DNase activity decreases on a similar timescale. These findings suggest that after fast target RNA cleavage the terminal RNA cleavage products stay bound within the Csm complex, keeping the Cas10 subunit activated for DNA destruction. Additionally, we demonstrate that during Cas10 activation, the complex remains capable of RNA turnover, i.e. of ongoing degradation of target RNA.

Bioactive dipeptides enhance the tolerance of lager yeast to ethanol-oxidation cross-stress by regulating the multilevel defense system

Although high gravity brewing technology has been widely used for beer industries due to its economic benefits, yeast cells are subjected to multiple environmental stresses throughout the fermentation process. Eleven bioactive dipeptides (LH, HH, AY, LY, IY, AH, PW, TY, HL, VY, FC) were selected to evaluate their effects on cell proliferation, cell membrane defense system, antioxidant defense system and intracellular protective agents of lager yeast against ethanol-oxidation cross-stress. Results showed that the multiple stresses tolerance and fermentation performance of lager yeast were enhanced by bioactive dipeptides. Cell membrane integrity was improved by bioactive dipeptides through altering the structure of macromolecular compounds of the cell membrane. Intracellular reactive oxygen species (ROS) accumulation was significantly decreased by bioactive dipeptides, especially for FC, decreasing by 33.1%, compared with the control. The decrease of ROS was closely related to the increase of mitochondrial membrane potential, intracellular antioxidant enzyme activities including superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD), and glycerol level. In addition, bioactive dipeptides could regulate the expression of key genes (GPD1, OLE1, SOD2, PEX11, CTT1, HSP12) to enhance the multilevel defense systems under ethanol-oxidation cross-stress. Therefore, bioactive dipeptides should be potentially efficient and feasible bioactive ingredients to improve the multiple stresses tolerance of lager yeast during high gravity fermentation.

Enforcing a Source-end Cooperative Multilevel Defense Mechanism to Counter Flooding Attack

The exponential advancement in telecommunication embeds the Internet in every aspect of communication. Interconnections of networks all over the world impose monumental risks on the Internet. A Flooding Attack (FA) is one of the major intimidating risks on the Internet where legitimate users are prevented from accessing network services. Irrespective of the protective measures incorporated in the communication infrastructure, FA still persists due to the lack of global cooperation. Most of the existing mitigation is set up either at the traffic starting point or at the traffic ending point. Providing mitigation at one or the other end may not be a complete solution. To insist on better protection against flooding attacks, this work proposes a cooperative multilevel defense mechanism. The proposed cooperative multilevel defense mechanism consists of two-level of mitigation. In the first level, it is proposed to design a Threshold-based rate-limiting with a Spoofing Resistant Tag (TSRT), as a source end countermeasure for High-Rate Flooding Attacks (HRFA) and spoofing attacks. In the second level, the accent is to discriminate normal traffic after Distributed Denial of Service (DDoS) traffic and drop the DDoS traffic at the destination end. Flow Congruence-based Selective Pushback (FCSP), as a destination-initiated countermeasure for the Low Rate Flooding Attack (LRFA). The source and the destination cooperate to identify and block the attack. A key advantage of this cooperative mechanism is that it can distinguish and channel down the attack traffic nearer to the starting point of the attack. The presentation of the agreeable cooperative multilevel safeguard mechanism is approved through broad recreation in NS-2. The investigation and the exploratory outcomes show that the proposed plan can effectively identify and shield from the attack.

Recent advances in molecular biology of metabolic syndrome pathophysiology: endothelial dysfunction as a potential therapeutic target

Current advances in molecular pathobiology of endotheliocytes dysfunctions are promising in finding the pathogenetic links to the emergence of insulin resistance syndrome. Physiologically, human organism homeostasis is strictly controlled to maintain metabolic processes at the acquainted level. Many factors are involved in maintaining these physiological processes in the organism and any deviation is undoubtedly accompanied by specific pathologies related to the affected process. Fortunately, the body's defense system can solve and compensate for the impaired function through its multi-level defense mechanisms. The endothelium is essential in maintaining this homeostasis through its ability to modulate the metabolic processes of the organism. Pathological activity or impairment of physiological endothelium function seems directly correlated to the emergence of metabolic syndrome. The most accepted hypothesis is that endothelium distribution is due to endoplasmic reticulum stress and unfolded protein response development, which includes inhibition of long non-coding RNAs expression, cytokines disbalance, Apelin dysregulation, glycocalyx degradation, and specific microparticles. Clinically, the enhancement or restoration of normal endothelial cells can be a target for novel therapeutic strategies since the distribution of its physiological activity impairs homeostasis and results in the progression of metabolic syndrome, and induction of its physiological activity can ameliorate insulin resistance syndrome. Novel insights on the molecular mechanisms of endothelial cell dysfunction are concisely represented in this paper to enhance the present therapeutic tactics and advance the research forward to find new therapeutic targets.

Molecular mechanisms underlying multi-level defense responses of horticultural crops to fungal pathogens.

The horticultural industry helps to enrich and improve the human diet while contributing to growth of the agricultural economy. However, fungal diseases of horticultural crops frequently occur during pre- and postharvest periods, reducing yields and crop quality and causing huge economic losses and wasted food. Outcomes of fungal diseases depend on both horticultural plant defense responses and fungal pathogenicity. Plant defense responses are highly sophisticated and are generally divided into preformed and induced defense responses. Preformed defense responses include both physical barriers and phytochemicals, which are the first line of protection. Induced defense responses, which include innate immunity (pattern-triggered immunity and effector-triggered immunity), local defense responses, and systemic defense signaling, are triggered to counterstrike fungal pathogens. Therefore, to develop regulatory strategies for horticultural plant resistance, a comprehensive understanding of defense responses and their underlying mechanisms is critical. Recently, integrated multi-omics analyses, CRISPR-Cas9-based gene editing, high-throughput sequencing, and data mining have greatly contributed to identification and functional determination of novel phytochemicals, regulatory factors, and signaling molecules and their signaling pathways in plant resistance. In this review, research progress on defense responses of horticultural crops to fungal pathogens and novel regulatory strategies to regulate induction of plant resistance are summarized, and then the problems, challenges, and future research directions are examined.

Research on Network Security Protection of Application-Oriented Supercomputing Center Based on Multi-Level Defense and Moderate Principle

High Performance Computing (HPC), also known as Supercomputing, is widely applied in various fields, which have the advantage of high processing capability and mass storage. Various open business services bring great threat to the network and data security of HPC cluster. This paper proposes a feasible scheme to realize supercomputing information security through multi-layer defense and overheads control according to the experience of operation, management and maintenance of Supercomputer Center for many years. First, this paper puts forward the principle of moderate risk, and gives the principles of design and the implementation for the security protection of Supercomputing Center. Second, this paper presents a security system architecture in coordination with deep collaborative defense. Finally, this paper designs a 4-layer protection scheme on account of the latest network security solutions and the operation and maintenance characteristic of our own supercomputer. Experiments on multi-level defense and overheads control show that the designed scheme takes into account the cost and network security, and obtain prospective results., which is especially suitable for the network security protection of small-scale or medium-scale high-performance computing cluster for engineering application.

Bienzymatic modification of polymeric membranes to mitigate biofouling

Staphylococcus aureus and Staphylococcus epidermidis are considered as major human pathogens and their resistance to antibiotic treatment and host defense systems can be increased due to the formation of biofilms. The biofilm-associated biofouling of industrial surfaces, particularly membranes, remains a serious concern that challenges investigators to develop practical solutions for the reduction of their impact. The present study developed antibacterial membrane surfaces that can mitigate biofilm formation. α-Amylase and lysozyme, as antibacterial enzymes, were covalently immobilized on polydopamine/cyanuric chloride functionalized polyethersulfone (PES) membranes to form biocompatible antibacterial surfaces. Several methods including SEM, AFM, Bradford, water contact angle goniometry, and surface free energy measurement techniques have been used to demonstrate the attachment of enzymes onto PES membranes by changing the physicochemical properties of the surface. The two enzymatic systems alter the membrane surface chemistry by rendering lower free surface energy and higher hydrophilicity, which leads to the creation of a layer of hydration energy barrier preventing microorganisms from being anchored on the surface. Those microorganisms that managed to overcome the energy barrier and get attached to the surface are attached by the enzymes' bond cleavage functionality. This multilevel defense system protects the membrane against any biofilm formation. The results of microtiter test and flow cytometry assay indicated that α-amylase/lysozyme mixture treated membrane samples came with more than 87% removal of biofilms. The results of the biofouling experiment in a dead-end cell demonstrated that the modified membrane surface had only a slightly impaired water flow compared to an unmodified membrane, which was due to the removal of biofilms by the enzymes’ activity. The results also showed that the modification of membranes with antibacterial enzymes could create a new biotechnological horizon to prevent biofilm formation.

Multi-level defense system models: overcoming by means of attacks with several phase constraints

The Germeyer “defense–attack” model is modified to allow for an echeloned defence system in a given direction. The model is a special case of the terminal-type discrete optimal control problem, and it can be solved using the subgradient-descent method. The posed control problem refines the resource level-distribution problem for a given direction, counting more general constraints with allowance for the action abilities of defense tools at various borders.

A Model of Overpowering a Multilevel Defense System by Attack

We consider a multilevel defense system on a given direction. This is a particular model of terminal discrete optimal control that may be solved by the gradient descent method. The main difficulty is the nondifferentiability of the Lipschitzian functions in the right-hand sides of the equation of motion and their derivatives with respect to all variables, which leads to an ill-posed problem when applying the classical results on differentiability of the terminal function and constructing its gradient from the conjugate system. A method is proposed for the solution of the problem by averaging the right-hand sides in combination with the stochastic gradient projection method. The study develops Germeier's defense-attack model by allowing for a multilevel defense structure, which in general leads to the synthesis problem for a discrete optimal control system.

English

BACKGROUND: Oral submucous fibrosis is a chronic progressive scarring disease of oral cavity and oropharynx characterized by epithelial atrophy and juxta epithelial inflammatory reaction with progressive fibrosis of the lamina propria an deeper connective tissue. In india, the first mention of this disease in literature dates back to the time of Sushruta as Vidari. However, in modern literature, Schwartz in 1952 first described it as atrophica idiopathica mucosaeoris. Antioxidants Protects by physically separating the free oxygen radicals from the susceptible molecules. Providing molecules that effectively compete with the oxygen. Rapidly repair the damage caused by the free radicals. Lysing & inactivating free radicals, removing damaged molecules. Body's multilevel defense systems against free radicals. AIMS & OBJECTIVES: The present study was undertaken to see effect of various antioxidant drugs on oral submucous fibrosis clinically as well histopathologically. MATERIAL & METHODS: This study comprises of 64 patients suffering from oral submucous fibrosis. History, examination and investigation of patients were done in detail as per predesigned proforma. OBSERVATIONS: Submucous fibrosis was seen from 2nd to 6th decade of life. Males were more commonly affected (65.625%) than females (34.375%). The incidence of submucous fibrosis is higher in Hindus (87.5%) than Muslims (12.5%). maximum number of the patients were between 1 and 2 years duration or between 5 and 10 years duration (16 cases in each group. Table shows that 50% of the patients suffering from oral submucous fibrosis had been chewing pan - masala and betel nut. In our series of study maximum cases were of severe grade trismus (32.81%). In this study we gave antioxidants drugs to the patients for a period of 2-3 months. Symptoms of burning sensation of mouth were relieved in 64.51% of cases by antioxidant therapy. Repeated painful ulcerations of mouth were relieved in 70% cases by antioxidant therapy. Suppleness of oral tissue was improved in 80.00% cases by antioxidant therapy. The symptom of trismus was relieved in 26.19% cases by antioxidant therapy. Out of 64 cases of oral submucous fibrosis 36 cases improved on therapy (56.25%) No patient got complete cure by therapy and there were 16 cases who failed on therapy (25%). There were 12 cases (18.75%) that did not come for follow up. CONCLUSION: Thus our work is showing that anti-oxidant drugs are overall favourable for early cases of oral submucous fibrosis clinically as well as histopathologically. So we conclude that anti-oxidant therapy should be regularly used in cases of oral submucous fibrosis.

Alerted Defense System Attenuates Hypersensitive Response-Associated Cell Death in Arabidopsis siz1 Mutant

Plants defend themselves by inducing sophisticated multilevel defense responses against pathogenic attack. The first line of defense against microbial pathogens is the process of nonself-recognition, which mediates the activation of the necessary defense repertoire. The hypersensitive response (HR), a macroscopic collapse of plant leaves in primary infection site, is one of such plant resistance responses. Subsequently, the HR triggers a general resistance mechanism called systemic acquired resistance (SAR), rendering uninfected parts of the plants less sensitive to further pathogenic attacks. Here, we show that SIZ1 mutation-mediated preexisting SAR attenuates HR-associated cell death in Arabidopsis thaliana. In siz1 mutant, the amount of PR1 and PR5 stayed high level, and the growth of pathogenic bacteria Pseudomonas syringae pv. maculicola (Pma) strain M6CΔE was reduced. Early callose deposition, spontaneous formation of microscopic cell death, and reactive oxygen species (ROS) were also observed in siz1 mutant.

Expression of phospholipid hydroperoxide glutathione peroxidase in human tumor cell lines

Free radical-induced damage in cells is thought to be involved in the initiation and/or promotion of many cancers. A multilevel antioxidant defense system effective in the protection against free radical damage includes chain-breaking antioxidants and enzymes, such as superoxide dismutase, catalase, and glutathione peroxidases. These latter, glutathione peroxidase (PGX) and phospholipid hydroperoxide glutathione peroxidase (PHGPX), are the only selenoperoxidases present in cells and have been distinct on the basis of mol wt, substrate specificity, and peptide and cDNA fragment sequencing. The ability of PHGPX to reduce phospholipid and cholesterol hydroperoxides accounts for its ability, which is not shared with GPX, to protect membrane from lipid peroxidation, in cooperation with vitamin E. PHGPX was identified in a wide range of mammalian tissues-red blood cells being a notable exceptionand has been recently detected in human tumor-derived cells lines-MCF 7, K 562, HL 60, their doxorubicin resistant variant ADR R, and Hep G2after growth in selenium-sufficient medium. PHGPX specific activity in these cells ranged between 7-22 nmol/min/mg protein. The location of the enzyme was found to be mainly cytosolic, but 3-10% of the total activity was detected in the membrane fraction, whereas 15% of the total activity was detected in the nuclear fraction. The cytosolic enzyme was identified among the radiolabeled selenioproteins present in HEP G2 and

Inverse correlation between essential antioxidants in plasma and subsequent risk to develop cancer, ischemic heart disease and stroke respectively: 12-year follow-up of the Prospective Basel Study.

There is accumulating evidence that free radicals may contribute to various diseases such as cancer or cardiovascular disease. Possible health hazards can to some extent be prevented by the body's multilevel defense system against free radicals, which comprises, besides others, antioxidant vitamins. The 12-year mortality follow-up of 2,974 participants of the Basal Study allowed to test the hypothesis that low antioxidant vitamin plasma concentrations (vitamin A, C, E and carotene) were associated with increased death from cancer of various sites and death from atherosclerosis such as ischemic heart disease and stroke, respectively. For the analysis 204 cancer cases, 132 fatalities from ischemic heart disease (IHD) and 31 deaths from cerebral vascular disease were available. Cancer mortality. Overall mortality from cancer was associated with low mean plasma levels of carotene adjusted for cholesterol (p less than 0.01) and of vitamin C (p less than 0.01). Bronchus and stomach cancers were associated with a low mean plasma carotene level (p less than 0.01). Subjects with subsequent stomach cancer had also lower mean vitamin C and lipid-adjusted vitamin A levels than survivors (p less than 0.05). Calculating the relative risk with exclusion of mortality during the first two years of follow-up, low plasma carotene was associated with an increased risk for bronchus cancer (RR 1.8, p less than 0.05), and the small number of stomach cancer cases (RR 2.95, p less than 0.05) low plasma levels of carotene and vitamin A with all cancer types (RR 2.47, p less than 0.01), and low plasma retinol in older subjects (greater than 60 years) with lung cancer (RR 2.17, p less than 0.05). Studies in other cohorts with a poor vitamin E status revealed an increased risk of subsequent cancer at low vitamin E levels as well. It is concluded that low plasma levels of all major essential antioxidants are associated with an increased risk of subsequent cancer mortality. Cardio-vascular mortality. Plasma carotene concentration below quartile 1 was associated with an increased risk for IHD (RR 1.53, p = 0.02). The same was true for low levels of both carotene and vitamin C (RR = 1.96, p = 0.022). The risk of cerebrovascular death was elevated in subjects with low carotene in the presence of low vitamin C plasma concentration (RR 4.17, p less than 0.01). These data confirm and extend recent findings on an inverse correlation of beta-carotene and vitamin C respectively to CVD.(ABSTRACT TRUNCATED AT 400 WORDS)