Adaptive Tolerance Research Articles

Development of nanocubosomes co-loaded with dual anticancer agents curcumin and temozolomide for effective colon cancer therapy

Current research aimed to develop nanocubosomes co-loaded with dual anticancer drugs curcumin and temozolomide for effective colon cancer therapy. Drugs co-loaded nanocubosomal dispersion was prepared by modified emulsification method using glyceryl monooleate (GMO), pluronic F127 and bovine serum albumin (BSA) as a lipid phase, surfactant, and stabilizer, respectively. The resulting nanocubosomes were characterized by measuring hydrodynamic particle size, particle size distribution (PSD), drug loading capacity (DL), encapsulation efficiency (EE), colloidal stability and drug release profile. We also physiochemically characterized the nanocubosomes by transmission electron microscopy (TEM), Fourier transform infrared (FTIR), and x-rays diffraction (XRD) for their morphology, polymer drug interaction and its nature, respectively. Further, the in-vitro cell-uptake, mechanism of cell-uptake, in-vitro anti-tumor efficacy and apoptosis level were evaluated using HCT-116 colon cancer cells. The prepared nanocubosomes exhibited a small hydrodynamic particle size (PS of 150 ± 10 nm in diameter) with nearly cubic shape and appropriate polydispersity index (PDI), enhanced drug loading capacity (LC of 6.82 ± 2.03% (Cur) and 9.65 ± 1.53% (TMZ), high entrapment efficiency (EE of 67.43 ± 2.16% (Cur) and 75.55 ± 3.25% (TMZ), pH-triggered drug release profile and higher colloidal stability in various physiological medium. Moreover, the nanocubosomes showed higher cellular uptake, in-vitro cytotoxicity and apoptosis compared to free drugs, curcumin and temozolomide, most likely because its small particle size. In addition, BSA-stabilized nanocubosomes were actively taken by aggressive colon cancer cells that over-expressed the albumin receptors and utilized BSA as nutrient source for their growth. In short, this study provides a new and simple strategy to improve the efficacy and simultaneously overawed the adaptive treatment tolerance in colon cancer.

Listeria monocytogenes Pathogenesis: The Role of Stress Adaptation.

Adaptive stress tolerance responses are the driving force behind the survival ability of Listeria monocytogenes in different environmental niches, within foods, and ultimately, the ability to cause human infections. Although the bacterial stress adaptive responses are primarily a necessity for survival in foods and the environment, some aspects of the stress responses are linked to bacterial pathogenesis. Food stress-induced adaptive tolerance responses to acid and osmotic stresses can protect the pathogen against similar stresses in the gastrointestinal tract (GIT) and, thus, directly aid its virulence potential. Moreover, once in the GIT, the reprogramming of gene expression from the stress survival-related genes to virulence-related genes allows L. monocytogenes to switch from an avirulent to a virulent state. This transition is controlled by two overlapping and interlinked transcriptional networks for general stress response (regulated by Sigma factor B, (SigB)) and virulence (regulated by the positive regulatory factor A (PrfA)). This review explores the current knowledge on the molecular basis of the connection between stress tolerance responses and the pathogenesis of L. monocytogenes. The review gives a detailed background on the currently known mechanisms of pathogenesis and stress adaptation. Furthermore, the paper looks at the current literature and theories on the overlaps and connections between the regulatory networks for SigB and PrfA.

The Application of Adaptive Tolerance and Serialized Facial Feature Extraction to Automatic Attendance Systems

The aim of this study was to develop a real-time automatic attendance system (AAS) based on Internet of Things (IoT) technology and facial recognition. A Raspberry Pi camera built into a Raspberry Pi 3B is used to transfer facial images to a cloud server. Face detection and recognition libraries are implemented on this cloud server, which thus can handle all the processes involved with the automatic recording of student attendance. In addition, this study proposes the application of data serialization processing and adaptive tolerance vis-à-vis Euclidean distance. The facial features encountered are processed using data serialization before they are saved in the SQLite database; such serialized data can easily be written and then read back from the database. When examining the differences between the facial features already stored in the SQLite databases and any new facial features, the proposed adaptive tolerance system can improve the performance of the facial recognition method applying Euclidean distance. The results of this study show that the proposed AAS can recognize multiple faces and so record attendance automatically. The AAS proposed in this study can assist in the detection of students who attempt to skip classes without the knowledge of their teachers. The problem of students being unintentionally marked present, though absent, and the problem of proxies is also resolved.

Adaptive active fault-tolerant MPPT control of variable-speed wind turbine considering generator actuator failure

In order to ensure that the wind power system (WPS) can realize maximum power point tracking (MPPT) under generator side fault, an MPPT control system with adaptive active fault tolerance capability is proposed in this paper. The basic idea of the proposed control strategy is that a perturbation term containing model uncertainties, system nonlinearities and unknown disturbances (generator actuator failure and disturbance torque) is estimated in real-time by a designed observer. The estimated perturbation is used for the compensation of actual perturbation. Then, an adaptive feedback linearizing control of variable-speed wind turbine (VSWT) system can be realized. Therefore, the control strategy neither requires detailed system model and full state measurements, nor relies on fault detection, diagnosis and isolation techniques when the generator actuator fails. Simulation results show that the proposed control scheme has smaller tracking error and better dynamic performance than the traditional PI control and MPPT control, and higher robustness against system parameter uncertainties, disturbance torque and generator actuator failure than the nonlinear static state feedback based MPPT (NSSF-MPPT) control, traditional PI control and MPPT control.

Screening Root Traits of Rice Landraces Seedlings (Oryza sativa L.) Under Induced Drought Stress using Hydroponic System

Drought is one of the most abiotic stress factor that limit the rice production worldwide. Drought stress induces the osmotic stress to plants. This study was conducted under hydroponics system with the three rice landraces 337 – IC116006, 101 – IC464685 and 224 – IC463809 along with drought tolerant check variety Anna (R) 4 under drought stress during seedling stage. The treatments were applied at 20 days old seedlings by imposing stress with PEG 6000 (-7 bar) along with control. The root traits viz., root length, root fresh weight, root dry weight, root volume, root tissue density and lateral root numbers were measured ten days after stress. In this study, the landrace 337 – IC116006 was observed as a tolerant, 101- IC464685 was observed as a moderately tolerant whereas landrace 224- IC463809 was observed as a susceptible. The root traits are the indicators which could contribute for the vigour and growth of the rice landraces at their later stage. The positive adaptive drought tolerance of rice landraces during seedling stage can be utilized as a trait in the breeding programs development for the drought tolerant cultivar.

Assessing the Effect of Physicochemical Properties of Saline and Sodic Soil on Soil Microbial Communities

Soil physicochemical properties are the main driving factors affecting the stability and diversity of the soil microbial community. The impacts of the saline–alkali situation and associated soil degradation need to be understood and reversed as soil diversity and communities are increasingly affected by saline–alkaline soil. However, the differences between salinization and alkalization soil and their impact on microbiota have been overlooked. The object of this study is to demonstrate the differences in salinization and alkalization soil and the driving factors affecting microbiota. In this study, 12 soil samples collected from saline–alkaline spots were used to detect the differences in soil physicochemical properties. The soil microbial community was sequenced by high-throughput sequencing. The results of ESP and EC in the soil samples indicated that the soil samples were categorized as saline soil and sodic soil. Venn diagrams indicated that unique OTUs in saline soil showed higher adaptation and environmental tolerance. Partial Mantel tests showed that the differences in pH, exchangeable sodium percentage (ESP), C/N, Na, and K between saline and sodic soil were the primary determinants affecting the relative abundance of bacterial and fungal communities, besides electrical conductivity (EC). In the KEGG analysis, ESP mainly affected the cellular processes in the archaea. Metabolism in the bacterial function was positively correlated with K only in sodic soil. These results indicated that the proportions in sodic soil were more strongly affecting soil microbiota.

Intestinal inflammation alters the antigen-specific immune response to a skin commensal.

SUMMARYResident microbes in skin and gut predominantly impact local immune cell function during homeostasis. However, colitis-associated neutrophilic skin disorders suggest possible breakdown of this compartmentalization with disease. Using a model wherein neonatal skin colonization by Staphylococcus epidermidis facilitates generation of commensal-specific tolerance and CD4+ regulatory T cells (Tregs), we ask whether this response is perturbed by gut inflammation. Chemically induced colitis is accompanied by intestinal expansion of S. epidermidis and reduces gut-draining lymph node (dLN) commensal-specific Tregs. It also results in reduced commensal-specific Tregs in skin and skin-dLNs and increased skin neutrophils. Increased CD4+ circulation between gut and skin dLN suggests that the altered cutaneous response is initiated in the colon, and resistance to colitis-induced effects in Cd4creIl1r1fl/fl mice implicate interleukin (IL)-1 in mediating the altered commensal-specific response. These findings provide mechanistic insight into observed connections between inflammatory skin and intestinal diseases.

Enhancement of Simulation CPU Time of Reactive-Transport Flow in Porous Media: Adaptive Tolerance and Mixing Zone-Based Approach

Enhancement of Simulation CPU Time of Reactive-Transport Flow in Porous Media: Adaptive Tolerance and Mixing Zone-Based Approach

Effects of Iron Deficiency Stress on Plant Growth and Quality in Flowering Chinese Cabbage and Its Adaptive Response

Iron (Fe) plays an important role in the growth and development of plants. The effects of different Fe concentrations, 1-aminocyclopropane-1-carboxylic acid (ACC), and cobalt chloride (Co2+) treatments on plant growth, quality and the adaptive response to Fe deficiency stress were investigated in flowering Chinese cabbage. The results revealed that Fe deficiency stress inhibited plant growth. The contents of vitamin C, soluble protein, and soluble sugar in leaves and stalks were significantly reduced under Fe deficiency stress, while the content of cellulose and nitrate was increased. Fe deficiency stress clearly reduced the net photosynthetic rate and nitrate reductase activity in the leaves. The balance system of active oxygen metabolism was destroyed due to Fe deficiency, resulting in the decrease in catalase activity, superoxide dismutase activity of roots and leaves, and peroxidase (POD) activity of leaves, while POD activity in roots and malonaldehyde content in roots and leaves were significantly increased. The treatments of Fe deficiency and ACC significantly reduced the pH value of the root medium, promoted the release of ethylene, and increased Fe3+ reductase activity, while Co2+ treatment showed results that were the opposite to those of Fe deficiency and ACC treatments. Thus, Fe deficiency stress affected nitrogen metabolism, photosynthesis, reactive oxygen metabolism, pH of root medium, and Fe3+ reductase activity, which was related to physiological adaptive response and tolerance mechanisms. We also found that ethylene could be involved in regulating the adaptive response to Fe deficiency stress in flowering Chinese cabbage.

Can We Arrest the Evolution of Antibiotic Resistance? The Differences between the Effects of Silver Nanoparticles and Silver Ions

Silver nanoparticles (AgNPs) are effective antimicrobial substances that show promise in combatting multidrug resistance. The potential application and release of AgNPs into the environment may neutralize the selective advantage of antibiotic resistance. Systemic knowledge regarding the effect of NPs on the evolution of antibiotic resistance is lacking. Our results showed that bacteria slowly developed adaptive tolerance to ciprofloxacin (CIP) under cyclic CIP and silver ion (Ag+) cotreatment, and no resistance/tolerance was discernible when CIP and AgNP exposure was alternated. In contrast, rapid CIP resistance was induced under continuous selection by treatment with only CIP. To combat the effects of CIP and Ag+, bacteria developed convergent evolutionary strategies with similar adaptive mechanisms, including anaerobic respiration transitioning (to reduce oxidative stress) and stringent response (to survive harsh environments). Alternating AgNP exposure impeded evolutionary resistance by accelerating B12-dependent folate and methionine cycles, which reestablished DNA synthesis and partially offset high oxidative stress levels, in contrast with the effect of CIP-directed evolutionary pressure. Nevertheless, CIP/AgNP treatment was ineffective in attenuating virulence, and CIP/Ag+ exposure even induced the virulence-critical type III secretion system. Our results increase the basic understanding of the impacts of NPs on evolutionary biology and suggest prospective nanotechnology applications for arresting evolutionary antibiotic resistance.

Evidence for evolution and selection of drought-resistant genes based on high-throughput resequencing in weedy rice.

Weedy rice (Oryza sativa f. spontanea) is a relative of cultivated rice that propagates in paddy fields and has strong drought resistance. In this study, we used 501 rice accessions to reveal the selection mechanism of drought resistance in weedy rice through a combination of selection analysis, genome-wide association studies, gene knockout and overexpression analysis, and Ca2+ and K+ ion flux assays. The results showed that the weedy rice species investigated have gene introgression with cultivated rice, which is consistent with the hypothesis that weedy rice originated from de-domestication of cultivated rice. Regions related to tolerance have particularly diversified during de-domestication and three drought-tolerance genes were identified. Of these, Os01g0800500 was also identified using an assay of the degree of leaf withering under drought, and it was named as PAPH1, encoding a PAP family protein. The drought-resistance capacity of PAPH1-knockout lines was much lower than that of the wild type, while that of overexpression lines was much higher. Concentrations of Ca2+ and K+ were lower in the knockout lines and higher in the overexpression lines compared with those of the wild type, suggesting that PAPH1 plays important roles in coping with drought stress. Our study therefore provides new insights into the genetic mechanisms underlying adaptive tolerance to drought in wild rice and highlights potential new resistance genes for future breeding programs in cultivated rice.

Genetic Diversity and Its Impact in Enhancement of Crop Plants

Plant breeding is a science that focuses on the development of new plant varieties in a systematic and ongoing method. It takes advantage of genetic variation among individuals within a plant species and combines desired traits to produce new and improved varieties. Plant breeding depends on genetic variety, and new variation is critical for introducing interesting characteristics into breeding programs. Genetic erosion is a term used to describe the loss of variation in crops as a result of agricultural modernization. Plant breeding has had a significant impact on food production and will continue to play an important role in ensuring global food security. Plant breeding can be broadly described as changes in plants caused by human use, ranging from unintended modifications generated by the introduction of agriculture through the use of molecular tools for precision breeding. Plant breeding based on observed variation by selection of plants based on natural variants appearing in nature or within traditional varieties; plant breeding based on controlled mating by selection of plants presenting recombination of desirable genes from different parents; and plant breeding based on monitored recombination by selection of specific genes or marker profiles. Continuous use of traditional breeding methods in a given species may reduce the gene pool from which cultivars are derived, making crops more susceptible to biotic and abiotic challenges and impeding future advancement. Plant breeding's primary objectives are 'high yield, high quality, and quantity, extension of climate and soil adaptability ability, and tolerance or resistance to pests and diseases.' Plant breeders achieve these goals by exploiting genetic differences between plants. The range of the genetic base, as measured by genetic diversity, is a limiting factor in successful adaptation to environmental conditions and plant breeding. Many challenges in plant breeding require genetic variation, which can be found in the biodiversity of plant genetic resources such as breeding lines, landraces, primitive forms, wilds and wild relatives, and weed races.

Robust and scalable adaptive BDDC preconditioners for virtual element discretizations of elliptic partial differential equations in mixed form

The Virtual Element Method (VEM) is a recent numerical technology for the solution of partial differential equations on computational grids constituted by polygonal or polyhedral elements of very general shape. The aim of this work is to develop effective linear solvers for a general order VEM approximation designed to approximate three-dimensional scalar elliptic equations in mixed form. The proposed Balancing Domain Decomposition by Constraints (BDDC) preconditioner allows to use conjugate gradient iterations, albeit the algebraic linear systems arising from the discretization of the problem are indefinite, ill-conditioned, and of saddle point nature. The condition number of the resulting positive definite preconditioned system is adaptively controlled by means of deluxe scaling operators and suitable local generalized eigenvalue problems for the selection of optimal primal constraints. Numerical results confirm the theoretical estimates and the reliability of the adaptive procedure, with the experimental condition numbers always very close to the prescribed adaptive tolerance parameter. The scalability and quasi-optimality of the preconditioner are demonstrated, and the performances of the proposed solver are compared with state-of-the-art parallel direct solvers and block preconditioning techniques in a distributed memory setting.

Autoreactive antibodies control blood glucose by regulating insulin homeostasis

Homeostasis of metabolism by hormone production is crucial for maintaining physiological integrity, as disbalance can cause severe metabolic disorders such as diabetes mellitus. Here, we show that antibody-deficient mice and immunodeficiency patients have subphysiological blood glucose concentrations. Restoring blood glucose physiology required total IgG injections and insulin-specific IgG antibodies detected in total IgG preparations and in the serum of healthy individuals. In addition to the insulin-neutralizing anti-insulin IgG, we identified two fractions of anti-insulin IgM in the serum of healthy individuals. These autoreactive IgM fractions differ in their affinity to insulin. Interestingly, the low-affinity IgM fraction (anti-insulin IgMlow) neutralizes insulin and leads to increased blood glucose, whereas the high-affinity IgM fraction (anti-insulin IgMhigh) protects insulin from neutralization by anti-insulin IgG, thereby preventing blood glucose dysregulation. To demonstrate that anti-insulin IgMhigh acts as a protector of insulin and counteracts insulin neutralization by anti-insulin IgG, we expressed the variable regions of a high-affinity anti-insulin antibody as IgG and IgM. Remarkably, the recombinant anti-insulin IgMhigh normalized insulin function and prevented IgG-mediated insulin neutralization. These results suggest that autoreactive antibodies recognizing insulin are key regulators of blood glucose and metabolism, as they control the concentration of insulin in the blood. Moreover, our data suggest that preventing autoimmune damage and maintaining physiological homeostasis requires adaptive tolerance mechanisms generating high-affinity autoreactive IgM antibodies during memory responses.

Population genomics provides insights into lineage divergence and local adaptation within the cotton bollworm.

The cotton bollworm Helicoverpa armigera is a cosmopolitan pest and its diverse habitats plausibly contribute to the formation of diverse lineages. Despite the significant threat it poses to economic crops worldwide, its evolutionary history and genetic basis of local adaptation are poorly understood. In this study, we de novo assembled a high-quality chromosome-level reference genome of H. a. armigera (contig N50=7.34Mb), with 99.13% of the HaSCD2 assembly assigned to 31 chromosomes (Z-chromosome + 30 autosomes). We constructed an ultradense variation map across 14 cotton bollworm populations and identified a novel lineage in northwestern China. Historical inference showed that effective population size changes coincided with global temperature fluctuation. We identified nine differentiated genes in the three H. armigera lineages (H. a. armigera, H. a. conferta and the new northwestern Chinese lineage), of which per and clk genes are involved in circadian rhythm. Selective sweep analyses identified a series of Gene Ontology categories related to climate adaptation, feeding behaviour and insecticide tolerance. Our findings reveal fundamental knowledge of the local adaptation of different cotton bollworm lineages and will guide the formulation of cotton bollworm management measures at different scales.

Differential tolerance of Zymoseptoria tritici to altered optimal moisture conditions during the early stages of wheat infection

Foliar plant pathogens require liquid or vapour water for at least part of their development, but their response and their adaptive tolerance to moisture conditions have been much less studied than other meteorological factors to date. We examined the impact of altering optimal moisture conditions conducive to infection on the wheat-Zymoseptoria tritici interaction. We assessed the responses in planta of 48 Z. tritici strains collected in two climatologically distinct locations (Ireland and Israel) to four high moisture regimes differing in the timing and the duration of uninterrupted exposure to saturated relative humidity (100% RH) during the first three days of infection. Individual- and population-level moisture reaction norms expressing how the sporulating area of a lesion change with the RH conditions were established based on visual assessments of lesion development at 14, 17 and 20 days post-inoculation (dpi). Our findings highlighted: (i) a critical time-dependent effect on lesion development of uninterrupted periods of exposure to 100% RH during these earliest infection stages; (ii) a marked interindividual variation in the sensitivity to RH conditions both in terms of strain average moisture response and plasticity; (iii) a higher tolerance – expressed at 14 dpi, not later – of the Israeli population to early interruption of optimal moisture conditions. By indicating that sensitivity to sub-optimal moisture conditions may vary between individuals and populations, this study highlights the evidence of moisture adaptation signature in a plant pathogen. Understanding such variation is helpful to predict the response of pathogen populations to changing climatic conditions.

Adaptive tolerance: Protection through self‐recognition

The random nature of immunoglobulin gene segment rearrangement inevitably leads to the generation of self-reactive B cells. Avoidance of destructive autoimmune reactions is necessary in order to maintain physiological homeostasis. However, current central and peripheral tolerance concepts fail to explain the massive number of autoantibody-borne autoimmune diseases. Moreover, recent studies have shown that in physiological mouse models autoreactive B cells were neither clonally deleted nor kept in an anergic state, but were instead able to mount autoantibody responses. We propose that activation of autoreactive B cells is induced by polyvalent autoantigen complexes that can occur under physiological conditions. Repeated encounter of autoantigen complexes leads to the production of affinity-matured autoreactive IgM that protects its respective self-targets from degradation. We refer to this novel mechanism as adaptive tolerance. This article discusses the discovery of adaptive tolerance and the unexpected role of high affinity IgM autoantibodies.

Up-regulation of a stress-responsive endochitinase VvChit-IV in grapevine cell cultures improves in vitro stress tolerance.

Chitinases are pathogenesis-related proteins, which play an important role in plant growth regulation, defense mechanism, and stress tolerance. Embryogenic cultures from Vitis vinifera cv. Tempranillo exposed to in vitro stress exhibited the expression of an extracellular class IV endochitinase VvChit-IV. Phylogenetic and conserved motif analyses provided insights into the evolutionary relationships of chitinases. A computation-based investigation showed conserved domains and illustrated a chitin-binding site for chitin cleavage with a catalytic domain of glycoside hydrolase. Interestingly, gene expression pattern showed a differential expression of VvChit-IV associated with embryonic stress response to in vitro conditions. In response to in vitro stress, transcript level of VvChit-IV increased in embryogenic calli and cell suspensions and peaked at 1.5 and 3 folds, respectively, when compared to an internal reference gene. Evidence of tissue culture stress-induced endochitinase was reported here for the first time indicating that in vitro stress could mitigate elicitor application to induce chitinase expression and can stimulate an immune response against abiotic constraints. Data showed that up-regulation of VvChit-IV was associated with a substantial increase of H2O2 and proline without significant change in malondialdehyde content suggesting that the H2O2 signaling network might trigger a priming effect to boost the defense response against environmental stress. Endochitinase activation in plant stress mitigation was thus highlighted to improve tolerance through attenuation of oxidative stress. This study revealed that the grapevine endochitinase is promising for enhancing coping-oriented adaptation and abiotic stress tolerance, which gives new insights into its feasibility for use in cross-tolerance and crop improvement.

Analysis of photosynthetic adaptability and shade tolerance of lianas in riverside

This investigation aimed to study the photosynthetic adaptability and shade tolerance of liana in riverside green space. For this purpose, the illumination intensity gradient is set to 2000, 1800, 1500, 1200, 1000, 800, 600, 400, 200, 100, 0 μmol·m-2·s-1, and the corresponding net photosynthetic rate (Pn) value is determined. After the data on the photosynthetic tester is stable, read the value and repeat the measurement 3 times for each gradient; Net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (Cond), and intercellular CO2 concentration (Ci) were measured. Instantaneous water use efficiency (WUE) was calculated by Pn/Tr; Typha under different shading conditions was marked, and the leaf number, plant height, crown width, and other growth and development indicators of Typha were observed and recorded regularly. The data were analyzed by software to find out the law of the influence of shading on the growth of Typha. Results showed that the diurnal variation of net photosynthetic rate (Pn) of Typha and Canna showed a "single peak" curve in May and August, and there was no midday depression of photosynthesis, indicating that the two plants had strong adaptability to different light intensities. Shading has a significant impact on the growth of Typha. With the increase of shading degree, the plant height, leaf width and other indicators of Typha have a significant increasing trend, and there is a positive correlation. Still, it is not that the stronger the shading, the better. It is concluded that appropriate light and shade can promote the growth of liana in riverside green space.

Image defogging algorithm based on improved dark channel and adaptive tolerance

Image defogging algorithm based on improved dark channel and adaptive tolerance