Monolayer Protected Gold Nanoparticles: Application in Molecular Recognition

In the last years, a relevant attention has been paid to monolayer protected gold nanoparticles (AuNPs), which are nanometer-sized gold colloids coated with a monolayer of organic molecules. Indeed, they have several interesting features.The first one is the easiness to synthesize gold cores with various sizes. Second, the versatile chemistry of AuNPs allows the grafting of functional groups and co-factors onto their surface. Taking advantage of different kinds of non-covalent interactions (namely hydrophobic, ion pairing, and metal-ligand coordination), such functional groupscan in turn provide tailored binding sites for virtually any class of substrates. The variety of monolayers that can be potentially assembled endows a fine-tuning of these interactions not only in terms of selectivity, but also in terms of their strength. Therefore, AuNPs were emerging as great scaffolds for molecular recognition. In this thesis, chapter 1, the introductive chapter, will present the methods for the preparation of AuNPs, the recent progress of AuNPs as chemosensors and the approaches that have been developed to investigate the monolayer morphology of mixed AuNPs. In chapter 2, the aims and objectives of this thesis will be addressed. In chapter 3 and 4, a series of water soluble AuNPs were prepared and investigated as nanoreceptors and chemosensors using nuclear magnetic resonance (NMR) protocols. The results of chapter 3 indicated that by appropriate design of the coating ligands, the spontaneous formation of the sensing pockets in the monolayer of the gold nanoparticles can be achieved. The results in chapter 4 confirmed the possibility that the rational design of AuNPs with intrinsic binding cavities and controlled sensing ability can be aided by molecular dynamic (MD) simulations. In chapter 5, three kinds of positive charged AuNPs were prepared and they were able to detect and discriminate nonsteroidal anti-inflammatory drugs in a quantitative manner. In the field of molecular recognition, unique properties can also be obtained by the preparation of mixed AuNPs. Previous studies have already demonstrated that the morphology of the mixed monolayer is closely related to their properties. For this reason, in chapter 6, we will describe a method which combines NMR and electron paramagnetic resonance (EPR) techniques to investigate the morphology of mixed AuNPs. Furthermore, in chapter 7we demonstrated that the morphology of the mixed monolayer can be transformed when in the presence of proper interacting analytes

Nanoparticle-based receptors mimic protein-ligand recognition

The self-assembly of a monolayer of ligands on the surface of noble metal nanoparticles dictates the fundamental nanoparticle\u2019s behavior and its functionality. In this combined computational\u2013experimental study, we analyze the structure, organization, and dynamics of functionalized coating thiols in monolayer-protected gold nanoparticles (AuNPs). We explain how functionalized coating thiols self-organize through a delicate and somehow counterintuitive balance of interactions within the monolayer itself and with the solvent. We further describe how the nature and plasticity of these interactions modulate nanoparticle-based chemosensing. Importantly, we found that self-organization of coating thiols can induce the formation of binding pockets in AuNPs. These transient cavities can accommodate small molecules, mimicking protein-ligand recognition, which may explain the selectivity and sensitivity observed for different organic analytes in NMR chemosensing experiments. Thus, our findings advocate for the rational design of tailored coating groups to form specific recognition binding sites on monolayer-protected AuNPs

Astaxanthin production by Phaffia rhodozyma fermentation of cassava residues substrate

Cassava residues as main materials were fermented with Phaffia rhodozyma to produce astaxanthin.  Using the Box-Behnken design, the effects of sugar content, initial pH and nitrogen content were studied with the yield of astaxanthin as response value, which was evaluated to optimize the fermentation conditions of astaxanthin production.  The optimal fermentation conditions have been reached by the study: sugar content was 40 g/L, the initial pH was at 4 and nitrogen content was 8 g/L.  By validation test, the astaxanthin yield under the optimal condition, which was basically corresponded to the model prediction, was 96.83%.Keywords: astaxanthin, cassava recidues, Phaffia rhodozym

Compressor degradation management strategies for gas turbine aero-engine controller design

The Advisory Council for Aeronautics Research in Europe (ACARE) Flight Path 2050 focuses on ambitious and severe targets for the next generation of air travel systems (e.g., 75% reduction in CO2 emissions per passenger kilometre, a 90% reduction in NOx emissions, and a 65% reduction in the noise emissions of flying aircraft relative to the capabilities of typical new aircraft in 2000). Degradation is an inevitable phenomenon as aero-engines age with significant impacts on the engine performance, emissions level, and fuel consumption. The engine control system is a key element capable of coping with degradation consequences subject to the implementation of an advanced management strategy. This paper demonstrates a methodological approach for aero-engine controller adjustment to deal with degradation implications, such as emission levels and increased fuel consumption. For this purpose, a component level model for an aero-engine was first built and transformed to a block-structured Wiener model using a system identification approach. An industrial Min-Max control strategy was then developed to satisfy the steady state and transient limit protection requirements simultaneously while satisfying the physical limitation control modes, such as over-speed, surge, and over-temperature. Next, the effects of degradation on the engine performance and associated changes to the controller were analysed thoroughly to propose practical degradation management strategies based on a comprehensive scientometric analysis of the topic. The simulation results show that the proposed strategy was effective in restoring the degraded engine performance to the level of the clean engine while protecting the engine from physical limitations. The proposed adjustments in the control strategy reduced the fuel consumption and, as a result, the emission level and carbon footprint of the engine

Altered expression of maize PLASTOCHRON1 enhances biomass and seed yield by extending cell division duration

Maize is the highest yielding cereal crop grown worldwide for grain or silage. Here, we show that modulating the expression of the maize PLASTOCHRON1 (ZmPLA1) gene, encoding a cytochrome P450 (CYP78A1), results in increased organ growth, seedling vigour, stover biomass and seed yield. The engineered trait is robust as it improves yield in an inbred as well as in a panel of hybrids, at several locations and over multiple seasons in the field. Transcriptome studies, hormone measurements and the expression of the auxin responsive DR5(rev): mRFPer marker suggest that PLA1 may function through an increase in auxin. Detailed analysis of growth over time demonstrates that PLA1 stimulates the duration of leaf elongation by maintaining dividing cells in a proliferative, undifferentiated state for a longer period of time. The prolonged duration of growth also compensates for growth rate reduction caused by abiotic stresses

PCAT1 is a poor prognostic factor in endometrial carcinoma and associated with cancer cell proliferation, migration and invasion

Long non-coding RNAs (lncRNAs) are emerging as important modulators of cancer progression, among which prostate cancer-associated transcript 1 (PCAT1) has been shown to be an oncogene in several tumors. However, the clinical significance and biological function of PCAT1 in endometrial carcinoma (EC) remain unclear. In this study, we used 89 EC tissues and HEC-1B, Ishikawa, RL95-2 and AN3CA EC cell lines. We found elevated expression levels of PCAT1 in EC tissues and cell lines using reverse transcription qPCR (RT-qPCR). The prognostic value of PCAT1 was determined using Kaplan–Meier survival and Cox regression analysis. The results showed that higher PCAT1 expression was positively correlated with FIGO stage, myometrial invasion, lymph node metastasis, and a shorter overall survival. A series of functional assays showed that the knockdown of PCAT1 by small interfering RNA (siRNA) targeting PCAT1 (siPCAT1) suppressed cell proliferation, migration and invasion, but promoted apoptosis. Western blot analysis further showed that B-cell lymphoma 2 (Bcl-2), vimentin and N-cadherin were downregulated, but E-cadherin and Bcl-2-associated death promoter (Bad) were upregulated in PCAT1-silenced EC cells. Taken together, our results underscore the oncogenic role of PCAT1 in EC and show that PCAT1 may be a potential therapeutic target in EC treatment

Trichinella spiralis Infection Mitigates Collagen-Induced Arthritis via Programmed Death 1-Mediated Immunomodulation

Helminth infection induces Th2-biased immune responses and inhibitory/regulatory pathways that minimize excessive inflammation to facilitate the chronic infection of helminth in the host and in the meantime, prevent host hypersensitivity from autoimmune or atopic diseases. However, the detailed molecular mechanisms behind modulation on inflammatory diseases are yet to be clarified. Programmed death 1 (PD-1) is one of the important inhibitory receptors involved in the balance of host immune responses during chronic infection. Here, we used the murine model to examine the role of PD-1 in CD4+ T cells in the effects of Trichinella spiralis infection on collagen-induced arthritis (CIA). Mice infected with T. spiralis demonstrated higher expression of PD-1 in the spleen CD4+ T cells than those without infection. Mice infected with T. spiralis 2 weeks prior to being immunized with type II collagen displayed lower arthritis incidence and significantly attenuated pathology of CIA compared with those of uninfected mice. The therapeutic effect of T. spiralis infection on CIA was reversed by blocking PD-1 with anti-PD-1 antibody, associated with enhanced Th1/Th17 pro-inflammatory responses and reduced Th2 responses. The role of PD-1 in regulating CD4+ T cell differentiation and proliferation during T. spiralis infection was further examined in PD-1 knockout (PD-1−/−) C57BL/6 J mice. Interestingly, T. spiralis-induced alteration of attenuated Th1 and enhanced Th2/regulatory T cell differentiation in wild-type (WT) mice was effectively diminished in PD-1−/− mice characterized by recovered Th1 cytokine levels, reduced levels of Th2 and regulatory cytokines and CD4+CD25+Foxp3+ cells. Moreover, T. spiralis-induced CD4+ T cell proliferation suppression in WT mice was partially restored in PD-1−/− mice. This study introduces the first evidence that PD-1 plays a critical role in helminth infection-attenuated CIA in a mouse model by regulating the CD4+ T cell function, which may provide the new insights into the mechanisms of helminth-induced immunomodulation of host autoimmunity

第11回 千葉県門脈圧亢進症研究会 4.

BACKGROUND:Our previous studies showed that Trichinella spiralis paramyosin (TsPmy) is an immunomodulatory protein that inhibits complement C1q and C8/C9 to evade host complement attack. Vaccination with recombinant TsPmy protein induced protective immunity against T. spiralis larval challenge. Due to the difficulty in producing TsPmy as a soluble recombinant protein, we prepared a DNA vaccine as an alternative approach in order to elicit a robust immunity against Trichinella infection. METHODS AND FINDINGS:The full-length TsPmy coding DNA was cloned into the eukaryotic expression plasmid pVAX1, and the recombinant pVAX1/TsPmy was transformed into attenuated Salmonella typhimurium strain SL7207. Oral vaccination of mice with this attenuated Salmonella-delivered TsPmy DNA vaccine elicited a significant mucosal sIgA response in the intestine and a systemic IgG antibody response with IgG2a as the predominant subclass. Cytokine analysis also showed a significant increase in the Th1 (IFN-γ, IL-2) and Th2 (IL-4, 5, 6, 10) responses in lymphocytes from the spleen and MLNs of immunized mice upon stimulation with TsPmy protein. The expression of the homing receptors CCR9/CCR10 on antibody secreting B cells may be related to the translocation of IgA-secreted B cells to local intestinal mucosa. The mice immunized with Salmonella-delivered TsPmy DNA vaccine produced a significant 44.8% reduction in adult worm and a 46.6% reduction in muscle larvae after challenge with T. spiralis larvae. CONCLUSION:Our results demonstrated that oral vaccination with TsPmy DNA delivered by live attenuated S. typhimurium elicited a significant local IgA response and a mixed Th1/Th2 immune response that elicited a significant protection against T. spiralis infection in mice