Immune responses induced in HHD mice by multiepitope HIV vaccine based on cryptic epitope modification

CD8+ T cells play an important role in early HIV infection. However, HIV has the capacity to avoid specific CTL responses due to a high rate of mutation under selection pressure. Although the HIV proteins, gag and pol, are relatively conserved, these sequences generate low-affinity MHC-associated epitopes that are poorly immunogenic. Here, we applied an approach that enhanced the immunogenicity of low-affinity HLA-A2.1-binding peptides. The first position with tyrosine (P1Y) substitution enhanced the affinity of HLA-A2.1-associated peptides without altering their antigenic specificity. More importantly, P1Y variants efficiently stimulated in vivo native peptide-specific CTL that also recognized the corresponding naturally processed epitope. The potential to generate CTL against any low-affinity HLA-A2.1-associated peptide provides us with the necessary technique for identification of virus cryptic epitopes for development of peptide-based immunotherapy. Therefore, identification and modification of the cryptic epitopes of gal and pol provides promising candidates for HIV immunotherapy dependent upon efficient presentation by virus cells. Furthermore, this may be a breakthrough that overcomes the obstacle of immune escape caused by high rates of mutation. In this study, bioinformatics analysis was used to predict six low-affinity cryptic HIV gag and pol epitopes presented by HLA-A*0201. A HIV compound multi-CTL epitope gene was constructed comprising the gene encoding the modified cryptic epitope and the HIV p24 antigen, which induced a strong CD8+ T cell immune response regardless of the mutation. This approach represents a novel strategy for the development of safe and effective HIV prophylactic and therapeutic vaccines.     

The Cdx-2 polymorphism in the VDR gene is associated with increased risk of cancer: a meta-analysis

The Cdx-2 polymorphism in VDR gene has been extensively investigated for association with cancer risk, however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of the Cdx-2 polymorphism in VDR and cancer risk by meta-analysis. All eligible case–control studies were searched in Pubmed, Embase, CNKI and Wanfang databases. Odds ratios (OR) with the 95 % confidence intervals (CI) were used to assess the association. A total of 12,906 cases and 13,700 controls in 18 case–control studies were included. The results indicated that the AA homozygote carriers had a 16 % increased risk of cancer, when compared with the homozygote GG and heterozygote AG (OR = 1.16, 95 % CI 1.05–1.29 for AA vs. GG+AG). In the subgroup analysis by ethnicity, significant elevated risks were associated with AA homozygote carriers in Caucasians (OR = 1.16, 95 % CI 1.01–1.33, and P = 0.04) and African Americans (OR = 1.31, 95 % CI 1.07–1.61, and P = 0.01). In the subgroup analysis by cancer types, the polymorphism was associated with increased risk of breast cancer (OR = 1.23, 95 % CI 1.04–1.46, and P = 0.02). This meta-analysis suggested that the Cdx-2 polymorphism of VDR gene would be a risk factor for cancer. To further evaluate gene-to-gene and gene-to-environmental interactions between polymorphisms of VDR gene and cancer risk, more studies with large groups of patients are required.     

Involvement of putrescine and nitric oxide in aluminum tolerance by modulating citrate secretion from roots of red kidney bean

Background and Aims

Polyamines and nitric oxide (NO) are two important molecules modulating numerous environment stresses in plants. This study was to investigate the roles of polyamines and NO in aluminum (Al) tolerance in red kidney bean.

Methods

The interaction between putrescine (Put) and NO under Al stress was examined. NO donor and scavenger were used to further examine the role of NO in Al-induced citrate secretion from roots by high performance liquid chromatography.

Results

Al stress caused increase of endogenous free Put, and exogenous Put alleviated Al-induced inhibition of root elongation and Al accumulation. In addition, Put induced NO production and nitrate reductase (NR) activity under Al stress. Al- and Put-induced NO production could be reversed by NR inhibitor. Furthermore, Al stress stimulated citrate secretion from roots, and this response was stimulated by NO donor, whereas NO scavenger inhibited Al-induced citrate secretion from roots. Concomitantly, NO donor reduced Al accumulation in root apexes, while NO scavenger further enhanced Al accumulation. Al-induced inhibition of root growth was significantly improved by exogenous citrate treatment.

Conclusions

Put and NO enhanced Al tolerance by modulating citrate secretion from roots, and NO may act downstream of Put in red kidney bean under Al stress.     

Analytical methods for detecting pesticide switches with evolution of pesticide resistance

After a pest develops resistance to a pesticide, switching between different unrelated pesticides is a common management option, but this raises the following questions: (1) What is the optimal frequency of pesticide use? (2) How do the frequencies of pesticide applications affect the evolution of pesticide resistance? (3) How can the time when the pest population reaches the economic injury level (EIL) be estimated and (4) how can the most efficient frequency of pesticide applications be determined? To address these questions, we have developed a novel pest population growth model incorporating the evolution of pesticide resistance and pulse spraying of pesticides. Moreover, three pesticide switching methods, threshold condition-guided, density-guided and EIL-guided, are modelled, to determine the best choice under different conditions with the overall aim of eradicating the pest or maintaining its population density below the EIL. Furthermore, the pest control outcomes based on those three pesticide switching methods are discussed. Our results suggest that either the density-guided or EIL-guided method is the optimal pesticide switching strategy, depending on the frequency (or period) of pesticide applications.     

Nanoparticle-tethered NAD+ with in situ cofactor regeneration

A new and simple route for the preparation of immobilized NAD⁺ on carboxyl-activated silica nanoparticles activated by γ-aminpropyltriethoxysilane and glutaric anhydride was developed. In addition, formate dehydrogenase, keto-reductase and the silica nanoparticle-attached NAD⁺ were applied to catalyze the coupled reactions for production of l-lactate with the cofactor regenerated within the reaction cycle. As indicated by thermogravimetric analysis and FT-IR, the silica nanoparticles were successfully activated and the loading of carboxyl groups was 0.53 mmol g^?1 particle. The amount of immobilized NAD⁺ on the support was 73 mg g^?1 particle. With 0.2 M pyruvate and 3 M formate, 0.16 M l-lactate was produced after the coupled reactions. The immobilized system showed excellent efficiency and stabilities in recycling, and it retained 60 % residual activity even after six reuses.     

Normalization of miRNA qPCR high-throughput data: a comparison of methods

Low-density quantitative real-time PCR (qPCR) arrays are often used to profile expression patterns of microRNAs in various biological milieus. To achieve accurate analysis of expression of miRNAs, non-biological sources of variation in data should be removed through precise normalization of data. We have systematically compared the performance of 19 normalization methods on different subsets of a real miRNA qPCR dataset that covers 40 human tissues. After robustly modeling the mean squared error (MSE) in normalized data, we demonstrate lower variability between replicates is achieved using various methods not applied to high-throughput miRNA qPCR data yet. Normalization methods that use splines or wavelets smoothing to estimate and remove Cq dependent non-linearity between pairs of samples best reduced the MSE of differences in Cq values of replicate samples. These methods also retained between-group variability in different subsets of the dataset.     

The making of an ‘ideal’ live-in migrant care worker: recruiting,training, matching and disciplining

This essay investigates the contested processes through which gender and racial ideologies are practised and thereby place specific groups of women in particular gendered and racialized labour markets. The migration of female live-in care workers to Taiwan exemplifies how gender and racial ideologies are embodied in everyday practices that justify the paid care work done by these women and that produce their subordinate status. In this essay, I take the problematic of representation of ‘migrant care workers’ as a point of entry, to investigate how a gendered-racialized ideology is utilized to legitimate and naturalize the gendered-racialized division of care labour within the global capitalist context.     

Biomass accumulation and partitioning, photosynthesis, and photosynthetic induction in field-grown maize (Zea mays L.) under low- and high-nitrogen conditions

The objectives of this comparative study were to investigate the responses of biomass accumulation and partitioning to nitrogen supply and to examine the effect of low-nitrogen supply on the photosynthetic responses of maize leaves to steady-state and dynamic light. While the difference in leaf number and stem diameter was not statistically significant, there was a significant difference in plant height between the low-nitrogen and high-nitrogen maize plants. During grain-filling period, the ear leaf of the low-nitrogen maize plants possessed lower values of maximum photosynthetic rate, maximum stomatal conductance, maximum transpiration rate, apparent quantum yield, light compensate point, and carboxylation efficiency than did that of the high-nitrogen maize plants. Contrarily, lower values of intercellular CO₂ concentration and dark respiration rate were observed in the high-nitrogen maize plants. In addition, a slower response to simulated sunflecks was found in the ear leaf of the low-nitrogen maize plants; however, stomatal limitations did not operate in the ear leaf of the high-nitrogen or low-nitrogen maize plants during the photosynthetic induction. As compared to the high-nitrogen maize plants, the low-nitrogen maize plants accumulated much less plant biomass but allocated a greater proportion of biomass to belowground parts. In conclusion, our results suggested that steady-state photosynthetic capacity is restricted by both biochemical and stomatal limitation and the photosynthetic induction is constrained by biochemical limitation alone in low-nitrogen maize plants, and that maize crops respond to low-nitrogen supply in a manner by which more biomass was allocated preferentially to root tissues.     

Mechanisms for L-channel-mediated increase in [Ca]i and its reduction by anti-bipolar drugs in cultured astrocytes combined with its mRNA expression in freshly isolated cells support the importance of astrocytic L-channels

The importance of Ca²⁺ signaling in astrocytes is undisputed but a potential role of Ca²⁺ influx via L-channels in the brain in vivo is disputed, although expression of these channels in cultured astrocytes is recognized. This study shows that an increase in free cytosolic Ca²⁺ concentration ([Ca²⁺]_i) in astrocytes in primary cultures in response to an increased extracellular K⁺ concentration (45 mM) is inhibited not only by nifedipine (confirming previous observations) but also to a very large extent by ryanodine, inhibiting ryanodine receptor-mediated release of Ca²⁺, known to occur in response to an elevation in [Ca²⁺]_i. This means that the actual influx of Ca²⁺ is modest, which may contribute to the difficulty in demonstrating L-channel-mediated Ca²⁺ currents in astrocytes in intact brain tissue. Chronic treatment with any of the 3 conventional anti-bipolar drugs lithium, carbamazepine or valproic acid similarly causes a pronounced inhibition of K⁺-mediated increase in [Ca²⁺]_i. This is shown to be due to an inhibition of capacitative Ca²⁺ influx, reflected by decreased mRNA and protein expression of the ‘transient receptor potential channel’ (TRPC1), a constituent of store-operated channels (SOCEs). Literature data are cited (i) showing that depolarization-mediated Ca²⁺ influx in response to an elevated extracellular K⁺ concentration is important for generation of Ca²⁺ oscillations and for the stimulatory effect of elevated K⁺ concentrations in intact, non-cultured brain tissue, and (ii) that Ca²⁺ channel activity is dependent upon availability of metabolic substrates, including glycogen. Finally, expression of mRNA for Ca_v1.3 is demonstrated in freshly separated astrocytes from normal brain.