Increased Levels of p53 and PARP-1 in EL-4 Cells Probably Related with the Immune Adaptive Response Induced by Low Dose Ionizing Radiation in vitro

Objective This paper is to explore the DNA repair mechanism of immune adaptive response （AR） induced by low dose radiation （LDR）, the changes of mRNA levels and protein expressions of p53, ATM, DNA-PK catalytic subunit （DNA-PKcs） and PARP-1 genes in the LDR-induced AR in EL-4 cells. Methods The apoptosis and cell cycle progression of EL-4 cells were detected by flow cytometry in 12 h after the cells received the pre-exposure of 0.075 Gy X-rays （inductive dose, D 1） and the succeeding high dose irradiation （challenge dose, D2; 1.0, 1.5, and 2.0 Gy X-rays, respectively） with or without wortmannin （inhibitor of ATM and DNA-PK） and 3-aminobenzamid （inhibitor of PARP-1）. And the protein expressions and mRNA levels related to these genes were detected with flow cytometry and reverse transcription-polymerase chain reaction in 12 h after irradiation with D2. Results The mRNA and protein expressions of p53 and PARP-1 in EL-4 cells in the D1 ＋ D2 groups were much lower than those in the D2 groups, and those of PARP-1 in the 3-AB ＋ D2 and the 3-AB ＋ D1 ＋ D2 groups were much lower than those in the D2 and the D1 ＋ D2 groups. The percentage of apoptotic EL-4 cells in the 3-AB ＋ D1 ＋ D2 groups was much higher than that in the D1 ＋ D2 groups, that in the G0/G1 and the G2 ＋ M phases was much higher, and that in the S phase were much lower. Although the ATM and DNA-PKcs mRNA and protein expressions in wortmannin ＋ D1 ＋ D2 groups were much lower than those in the D1 ＋ D2 groups, there were no significant changes in the apoptosis and cell cycle progression between the wortmannin ＋ D1 ＋ D2 and the D1 ＋ D2 groups. Conclusion PARP-1 and p53 might play important roles in AR induced by LDR.

Effect of Cycloheximide on the Adaptive Response Induced by Low Dose Radiation

Human lymphocytes pre-exposed to 10 mGy or 50 mGy of X-rays become less sensitive to subsequent large dose irradiation, exhibited lower rate of chromosome aberration than expected. This adaptive response could be inhibited by cycloheximide, a protein synthesis inhibitor for successive 2 h period ranging from 0.5h before to 4h after the low dose exposure, indicating that the adaptive response was directly related with the protein synthesis.

Adaptive immune response during hepatitis C virus infection

Hepatitis C virus(HCV)infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma.HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control.Liver damage and disease progression during HCV infection are driven by both viral and host factors.Specifically,adaptive immune response carries out an essential task in controllingnon-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery.HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion.To impair HCV-specific T cell reactivity,HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro-and antiapoptotic proteins.In this review,the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.

Adaptive response of resistant cancer cells to chemotherapy

Despite advances in cancer therapeutics and the integration of personalized medicine,the development of chemoresistance in many patients remains a significant contributing factor to cancer mortality.Upon treatment with chemotherapeutics,the disruption of homeostasis in cancer cells triggers the adaptive response which has emerged as a key resistance mechanism.In this review,we summarize the mechanistic studies investigating the three major components of the adaptive response,autophagy,endoplasmic reticulum(ER)stress signaling,and senescence,in response to cancer chemotherapy.We will discuss the development of potential cancer therapeutic strategies in the context of these adaptive resistance mechanisms,with the goal of stimulating research that may facilitate the development of effective cancer therapy.

Induction of adaptive response in utero by ionizing radiation:A radiation quality dependent phenomenon

Investigation on possible induction of adaptive response(AR)by high-liner energy transfer(LET)particle radiation for protection against low-LET photon radiation-induced detrimental effects has not yet been performed in utero.This study verified if an AR could be induced by high-LET particle radiation from accelerated heavy ions against low-LET X-ray radiation-induced detrimental effects on fetal mice.Total body irradiation of pregnant C57BL/6J mice were performed by delivering a priming dose ranging from 10 mGy to 320 mGy of particle radiation on gestation day 11 followed one day later by a challenge dose at 3500 mGy from X-ray radiation.The monoenergetic beams of carbon,silicon and iron with the LET values of about 15,55,and 200 KeV/μm,respectively,were examined.Significant suppression by the priming radiation of the detrimental effects(fetal death,malformation,or low body weight)was used as the endpoints for judgment of a successful AR induction on gestation day 18.Existence of AR was not observed.On the other hand,the priming dose of high-LET particle radiation,in some cases,even increased the detrimental effects induced by the challenge dose from low-LET X-ray radiation.Although existence of AR induced by high-LET radiation in cultured mammalian cells in vitro and in certain tissues of laboratory mice in vivo was demonstrated,the present study did not suggest that low dose of high-LET particle radiation could induce an AR in fetal mice in utero under the setup of our experimental system.

Breed and adaptive response modulate bovine peripheral blood cells＇ transcriptome

Background： Adaptive response includes a variety of physiological modifications to face changes in external or internal conditions and adapt to a new situation. The acute phase proteins（APPs） are reactants synthesized against environmental stimuli like stress, infection, inflammation.Methods： To delineate the differences in molecular constituents of adaptive response to the environment we performed the whole-blood transcriptome analysis in Italian Holstein（IH） and Italian Simmental（IS） breeds. For this, 663 IH and IS cows from six commercial farms were clustered according to the blood level of APPs. Ten extreme individuals（five APP＋ and APP-variants） from each farm were selected for the RNA-seq using the Illumina sequencing technology. Differentially expressed（DE） genes were analyzed using dynamic impact approach（DIA）and DAVID annotation clustering. Milk production data were statistically elaborated to assess the association of APP＋ and APP-gene expression patterns with variations in milk parameters.Results： The overall de novo assembly of cDNA sequence data generated 13,665 genes expressed in bovine blood cells. Comparative genomic analysis revealed 1,152 DE genes in the comparison of all APP＋ vs. all APP-variants; 531 and 217 DE genes specific for IH and IS comparison respectively. In all comparisons overexpressed genes were more represented than underexpressed ones. DAVID analysis revealed 369 DE genes across breeds, 173 and 73 DE genes in IH and IS comparison respectively. Among the most impacted pathways for both breeds were vitamin B6 metabolism, folate biosynthesis, nitrogen metabolism and linoleic acid metabolism.Conclusions： Both DIA and DAVID approaches produced a high number of significantly impacted genes and pathways with a narrow connection to adaptive response in cows with high level of blood APPs. A similar variation in gene expression and impacted pathways between APP＋ and APP-variants was found between two studied breeds. Such similarity was also confirmed by annotation clustering of the DE genes. However, IH breed showed higher and more differentiated impacts compared to IS breed and such particular features in the IH adaptive response could be explained by its higher metabolic activity. Variations of milk production data were significantly associated with APP＋ and APP-gene expression patterns.

Adaptive Response of Wild and Mutant Type Synechococcus cedrorum to a Polychlorinated Pesticide-Endosulfan

The effect of endosulfan, a hexachlorinated pesticide, on growth, inorganic nitrogenous nutrient uptake (NO3-, NO2- and NH4+), change in pigmentation and glycogen content on wild type and chemically mutagenised cells of Synechococcus cedrorum was investigated. The pattern of response to pesticide stress in wild and mutant type was the same. Growth reappeared in both after a period of initial lag in presence of endosulfan. The duration of lag increased with increasing doses of pesticide. Paradoxically, however, the rate of uptake of NO-3, NO-2 and NH+4 pigment and glycogen content progressively increased with increasing doses. The difference in the adaptation response between wild and mutant types was observed only in the concentration of pesticide that could be tolerated; with the mutant tolerating 2.5 fold more.

Comparison of physiological responses to oxidative and heavy metal stress in seedlings of rice paddy, Oryza sativa L.

Physiological responses on the bases of activities of antioxidant enzymes: peroxidase, catalase, superoxide dismutase and glutathione reductase as well as estimation of total protein, lipid peroxidation and thiols in the form of protein, non\|protein, glutathione and phytochelatin measured in growing seedlings of paddy, Oryza sativa L., from day 2 to 8 were compared following treatment of seeds for 5h with oxidative agents, paraquat 5 × 10 -5 , 10 -4 , 10 -3 mol/L, H 2O 2 10 -3 , 5×10 -3 , 10 -2 mol/L, and CdCl 2 10 -5 , 10 -4 , 5×10 -3 mol/L. A significant induction of all antioxidant enzymes along with an increase in the levels of protein, lipid peroxidation and glutathione was noted in response to oxidative stress, CdCl 2 induced significant peroxidase and catalase activities but not superoxide dismutase. In a marked contrast from oxidative stress, CdCl 2 decreased glutathione reductase activity as well as glutathione levels but increased phytochelatin level. The different physiological responses thus underlined the crucial involvement of glutathione and phytochelatin in the oxidative and heavy metal\|linduced adaptive responses respectively.

Global Optimization Method Using SLE and Adaptive RBF Based on Fuzzy Clustering

High fidelity analysis models,which are beneficial to improving the design quality,have been more and more widely utilized in the modern engineering design optimization problems.However,the high fidelity analysis models are so computationally expensive that the time required in design optimization is usually unacceptable.In order to improve the efficiency of optimization involving high fidelity analysis models,the optimization efficiency can be upgraded through applying surrogates to approximate the computationally expensive models,which can greately reduce the computation time.An efficient heuristic global optimization method using adaptive radial basis function（RBF） based on fuzzy clustering（ARFC） is proposed.In this method,a novel algorithm of maximin Latin hypercube design using successive local enumeration（SLE） is employed to obtain sample points with good performance in both space-filling and projective uniformity properties,which does a great deal of good to metamodels accuracy.RBF method is adopted for constructing the metamodels,and with the increasing the number of sample points the approximation accuracy of RBF is gradually enhanced.The fuzzy c-means clustering method is applied to identify the reduced attractive regions in the original design space.The numerical benchmark examples are used for validating the performance of ARFC.The results demonstrates that for most application examples the global optima are effectively obtained and comparison with adaptive response surface method（ARSM） proves that the proposed method can intuitively capture promising design regions and can efficiently identify the global or near-global design optimum.This method improves the efficiency and global convergence of the optimization problems,and gives a new optimization strategy for engineering design optimization problems involving computationally expensive models.

Effects of surround suppression on response adaptation of V1 neurons to visual stimuli

The influence of intracortical inhibition on the response adaptation of visual cortical neurons remains in debate. To clarify this issue, in the present study the influence of surround suppression evoked through the local inhibitory interneurons on the adaptation effects of neurons in the primary visual cortex （V1） were observed. Moreover, the adaptations of V1 neurons to both the high-contrast visual stimuli presented in the classical receptive field （CRF） and to the costimulation presented in the CRF and the surrounding nonclassical receptive field （nCRF） were compared. The intensities of surround suppression were modulated with different sized grating stimuli. The results showed that the response adaptation of V1 neurons decreased significantly with the increase of surround suppression and this adaptation decrease was due to the reduction of the initial response of V1 neurons to visual stimuli. However, the plateau response during adaptation showed no significant changes. These findings indicate that the adaptation effects of V1 neurons may not be directly affected by surround suppression, but may be dynamically regulated by a negative feedback network and be finely adjusted by its initial spiking response to stimulus. This adaptive regulation is not only energy efficient for the central nervous system, but also beneficially acts to maintain the homeostasis of neuronal response to long-presenting visual signals.

Adaptive IIR filtering based on balanced-realization

Due to low parameter sensitivity for balanced realiza- tions, balanced structure becomes a good candidate for an statespace adaptive infinite impluse response （IIR） filter. Here, using coefficients of the transfer function as the adaptive filtering parameters, a balanced adaptive IIR filtering algorithm is proposed for output-error minimization. The algorithm in the internally balanced realization guarantees that the adaptive IIR filter always minimizes the ratio of maximum-to-minimum eigenvalue of the Grammian matrices at the each iteration. Simulation results are provided to corroborate the proposed algorithm.

Detecting and adaptive responding mechanism for mobile WSN

Mobile wireless sensor network(WSN)composed by mobile terminals has a dynamic topology and can be widely used in various fields.However,the lack of centralized control,dynamic topology and limited energy supply make the network layer of mobile WSN be vulnerable to multiple attacks,such as black hole(BH),gray hole(GH),flooding attacks(FA)and rushing attacks(RU).Existing researches on intrusion attacks against mobile WSN,currently,tend to focus on targeted detection of certain types of attacks.The defense methods also have clear directionality and is unable to deal with indeterminate intrusion attacks.Therefore,this work will design an indeterminate intrusion attack oriented detecting and adaptive responding mechanism for mobile WSN.The proposed mechanism first uses a test sliding window(TSW)to improve the detecting accuracy,then constructs parameter models of confidence on attack(COA),network performance degradation(NPD)and adaptive responding behaviors list,finally adaptively responds according to the decision table,so as to improve the universality and flexibility of the detecting and adaptive responding mechanism.The simulation results show that the proposed mechanism can achieve multiple types of intrusion detecting in multiple attack scenarios,and can achieve effective response under low network consumption.

Dynamic analysis of a latent HIV infection model with CTL immune and antibody responses

This paper develops a mathematical model to investigate the Human Immunodeficiency Virus(HIV)infection dynamics.The model includes two transmission modes(cell-to-cell and cell-free),two adaptive immune responses(cytotoxic T-lymphocyte(CTL)and antibody),a saturated CTL immune response,and latent HIV infection.The existence and local stability of equilibria are fully characterized by four reproduction numbers.Through sensitivity analyses,we assess the partial rank correlation coefficients of these reproduction numbers and identify that the infection rate via cell-to-cell transmission,the number of new viruses produced by each infected cell during its life cycle,the clearance rate of free virions,and immune parameters have the greatest impact on the reproduction numbers.Additionally,we compare the effects of immune stimulation and cell-to-cell spread on the model's dynamics.The findings highlight the significance of adaptive immune responses in increasing the population of uninfected cells and reducing the numbers of latent cells,infected cells,and viruses.Furthermore,cell-to-cell transmission is identified as a facilitator of HIV transmission.The analytical and numerical results presented in this study contribute to a better understanding of HIV dynamics and can potentially aid in improving HIV management strategies.

Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

It is well accepted that adaptive immunity plays a key role in the control of hepatitis B virus （HBV） infection. In contrast, the contribution of innate immunity has only received attention in recent years. Toll-like receptors （TLRs） sense pathogen-associated molecule patterns and activate antiviral mechanisms, including intracellular antiviral pathways and the production of antiviral effector interferons （IFNs） and pro-inflammatory cytokines. Experimental results from in vitroand in vivo models have demonstrated that TLRs mediate the activation of cellular signaling pathways and the production of antiviral cytokines, resulting in a suppression of HBV replication. However, HBV infection is associated with downregulation of TLR expression on host cells and blockade of the activation of downstream signaling pathways. In primary HBV infection, TLRs may slow down HBV infection, but contribute only indirectly to viral clearance. Importantly, TLRs may modulate HBV-specific T- and B-cell responses in vivo, which are essential for the termination of HBV infection. Thus, TLR agonists are promising candidates to act as immunomodulators for the treatment of chronic HBV infection. Antiviral treatment may recover TLR expression and function in chronic HBV infection and may increase the efficacy of therapeutic approaches based on TLR activation. A combined therapeutic strategy with antiviral treatment and TLR activation could facilitate the restoration of HBV-specific immune responses and thereby, achieve viral clearance in chronically infected HBV patients.

Cropping system innovation for coping with climatic warming in China

China is becoming the largest grain producing and carbon-emitting country in the world,with a steady increase in population and economic development.A review of Chinese experiences in ensuring food self-sufficiency and reducing carbon emission in the agricultural sector can provide a valuable reference for similar countries and regions.According to a comprehensive review of previous publications and recent field observations,China has experienced on average a larger and faster climatic warming trend than the global trend,and there are large uncertainties in precipitation change,which shows a non-significantly increasing trend.Existing evidence shows that the effects of climatic warming on major staple crop production in China could be markedly negative or positive,depending on the specific cropping region,season,and crop.However,historical data analysis and field warming experiments have shown that moderate warming,of less than2.0 °C,could benefit crop production in China overall.During the most recent warming decades,China has made successful adaptations in cropping systems,such as new cultivar breeding,cropping region adjustment,and cropping practice optimization,to exploit the positive rather than to avoid the negative effects of climatic warming on crop growth.All of these successful adaptations have greatly increased crop yield,leading to higher resource use efficiency as well as greatly increased soil organic carbon content with reduced greenhouse gas emissions.Under the warming climate,China has not only achieved great successes in crop production but also realized a large advance in greenhouse gas emission mitigation.Chinese experiences in cropping system innovation for coping with climatic warming demonstrate that food security and climatic warming mitigation can be synergized through policy,knowledge,and technological innovation.With the increasingly critical status of food security and climatic warming,further efforts should be invested in new agricultural policy,knowledge and technology creation,and popularization of climate-smart agriculture,and more financial investments should be made in field infrastructure development to increase cropping system resilience in China.

Many-lined Sun Skinks(Mabuya multifasciata) Shift Their Thermal Preferences Downwards When Fasted

We maintained adult many-lined sun skinks(Mabuya multifasciata; 12 females and 12 males) collected from Hainan(southern China) in September 2006 in two outdoor enclosures to examine the effect of feeding condition on selected body temperature(Tsel).Skinks shifted their thermal preferences when fasted.Temporal variation in Tsel was not found within each sex feeding condition combination,and neither in fed nor in fasted skinks did the mean values for Tsel differ between sexes.Body temperatures selected by fed skinks fell within the range from 30.2 to 33.9 C,and those selected by fasted skinks within the range from 25.1 to 31.8 C.Body temperatures(31.8 0.3 C) selected by fed skinks were on average 4.0 C higher than those(27.8 0.4 C) selected by fasted skinks.Fasted skinks had no difficulty in attaining higher body temperatures,but they voluntarily shift their thermal preferences downwards to save energy.This finding suggests an adaptive mechanism adopted by many-lined sun skinks to enhance their fitness during the periods when food availability is low.

COVID-19 and gut immunomodulation

The disease coronavirus disease 2019(COVID-19)is a severe respiratory illness that has emerged as a devastating health problem worldwide.The disease outcome is heterogeneous,and severity is likely dependent on the immunity of infected individuals and comorbidities.Although symptoms of the disease are primarily associated with respiratory problems,additional infection or failure of other vital organs are being reported.Emerging reports suggest a quite common co-existence of gastrointestinal(GI)tract symptoms in addition to respiratory symptoms in many COVID-19 patients,and some patients show just the GI symptoms.The possible cause of the GI symptoms could be due to direct infection of the epithelial cells of the gut,which is supported by the fact that(1)The intestinal epithelium expresses a high level of angiotensin-converting enzyme-2 and transmembrane protease serine 2 protein that are required for the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry into the cells;(2)About half of the severe COVID-19 patients show viral RNA in their feces and various parts of the GI tract;and(3)SARS-CoV-2 can directly infect gut epithelial cells in vitro(gut epithelial cells and organoids)and in vivo(rhesus monkey).The GI tract seems to be a site of active innate and adaptive immune responses to SARS-CoV-2 as clinically,stool samples of COVID-19 patients possess proinflammatory cytokines(interleukin 8),calprotectin(neutrophils activity),and immunoglobulin A antibodies.In addition to direct immune activation by the virus,impairment of GI epithelium integrity can evoke immune response under the influence of systemic cytokines,hypoxia,and changes in gut microbiota(dysbiosis)due to infection of the respiratory system,which is confirmed by the observation that not all of the GI symptomatic patients are viral RNA positive.This review comprehensively summarizes the possible GI immunomodulation by SARS-CoV-2 that could lead to GI symptoms,their association with disease severity,and potential therapeutic interventions.

Impact of SARS-CoV-2 on neuropsychiatric disorders

Evolving data show a variable expression of clinical neurological manifestations in patients suffering with coronavirus disease 2019(COVID-19)from early disease onset.The most frequent symptoms and signs are fatigue,dizziness,impaired consciousness,ageusia,anosmia,radicular pain,and headache,as well as others.Based on the high number of series of cases reported,there is evidence for the implication of the immune system in the pathological mechanism of COVID-19.Although the exact role of the immunological mechanism is not elucidated,two main mechanisms are suggested which implicate the direct effect of severe acute respiratory syndrome coronavirus 2 infection in the central nervous system and neuroinflammation.In the context of neurological manifestations associated with COVID-19,neuropsychiatric disorders show an exacerbation and are described by symptoms and signs such as depression,anxiety,mood alterations,psychosis,post-traumatic stress disorder,delirium,and cognitive impairment,which appear to be common in COVID-19 survivors.A worsened score on psychopathological measures is seen in those with a history of psychiatric comorbidities.We review the neuropsychiatric manifestations associated with COVID-19 and some critical aspects of the innate and adaptive immune system involved in mental health disorders occurring in COVID-19.

Interplay between ethylene and nitrogen nutrition:How ethylene orchestrates nitrogen responses in plants

The stress hormone ethylene plays a key role in plant adaptation to adverse environmental conditions.Nitrogen(N)is the most quantitatively required mineral nutrient for plants,and its availability is a major determinant for crop production.Changes in N availability or N forms can alter ethylene biosynthesis and/or signaling.Ethylene serves as an important cellular signal to mediate root system architecture adaptation,N uptake and translocation,ammonium toxicity,anthocyanin accumulation,and premature senescence,thereby adapting plant growth and development to external N status.Here,we review the ethylenemediated morphological and physiological responses and highlight how ethylene transduces the N signals to the adaptive responses.We specifically discuss the N-ethylene relations in rice,an important cereal crop in which ethylene is essential for its hypoxia survival.

Plant hormesis and Shelford’s tolerance law curve

Shelford’s law of tolerance is illustrated by a bell-shaped curve depicting the relationship between environmental factor/factors’intensity and its favorability for species or populations.It is a fundamental basis of ecology when considering the regularities of environment impacts on living systems,and applies in plant biology,agriculture and forestry to manage resistance to environmental limiting factors and to enhance productivity.In recent years,the concept of hormesis has been increasingly used to study the dose-response relationships in living organisms of different complexities,including plants.This requires the need for an analysis of the relationships between the hormetic dose-response model and the classical understanding of plant reactions to environments in terms of Shelford’s law of tolerance.This paper analyses various dimensions of the relationships between the hormetic model and Shelford’s tolerance law curve under the influence of natural environmental factors on plants,which are limiting for plants both in deficiency and excess.The analysis has shown that Shelford’s curve and hormetic model do not contradict but instead complement each other.The hormetic response of plants is localized in the stress zone of the Shelford’s curve when adaptive mechanisms are disabled within the ecological optimum.At the same time,in a species range,the ecological optimum is the most favorable combination of all or at least the most important environmental factors,each of which usually deviates slightly from its optimal value.Adaptive mechanisms cannot be completely disabled in the optimum,and hormesis covers optimum and stress zones.Hormesis can modify the plant tolerance range to environmental factors by preconditioning and makes limits of plant tolerance to environmental factors flexible to a certain extent.In turn,as a result of tolerance range evolution,quantitative characteristics of hormesis(width and magnitude of hormetic zone)as well as the range of stimulating doses,may significantly differ in various plant species and even populations and intra-population groups,including plants at different development stages.Using hormetic preconditioning for managing plant resistance to environmental limiting factors provides an important perspective for increasing the productivity of woody plants in forestry.