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STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti–IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

Many red-skinned apple cultivars grown under warm summer conditions do not redden as much as those grown in locations with cooler summer temperatures. Reflective films and over-tree sprinkler irrigation have been used to mitigate the issue. However, the most efficient strategy is to breed new cultivars that have a high genetic potential for fruit colour development under warmer climates. New cultivars selected for their adaptation to such climates are being bred by a joint Institut de Recerca i Tecnologia Agroalimentaries-Plant & Food Research (IRTA-PFR) breeding programme. Understanding the physiological and genetic control of the response to warm orchard temperature is crucial for developing new tools for more efficient breeding of red-skinned apple cultivars. We manipulated fruit skin temperature by heating and cooling 'Royal Gala' fruit in orchards in New Zealand and Spain and measured the expression of the genes regulating red pigmentation. Evidence of down-regulation of the main activator of red pigmentation (MYBIO) was demonstrated, and this gene is linked to a locus controlling the red-skinned phenotype. A marker based on MYB10 was developed and is now used for marker-assisted breeding of new apple cultivars suited to warm conditions. [ABSTRACT FROM AUTHOR]

The innate immune system senses cytosolic dsDNA and bacterial cyclic dinucleotides and initiates signaling via the adaptor STING to induce type 1 interferon (IFN) response. We demonstrate here that BTK-deficient cells have impaired IFN-β production and TBK1/IRF3 activation when stimulated with agonists or infected with pathogens that activate STING signaling. BTK interacts with STING and DDX41 helicase. The kinase and SH3/SH2 interaction domains of BTK bind, respectively, the DEAD-box domain of DDX41 and transmembrane region of STING. BTK phosphorylates DDX41, and its kinase activities are critical for STING-mediated IFN-β production. We show that Tyr364 and Tyr414 of DDX41 are critical for its recognition of AT-rich DNA and binding to STING, and tandem mass spectrometry identifies Tyr414 as the BTK phosphorylation site. Modeling studies further indicate that phospho-Tyr414 strengthens DDX41’s interaction with STING. Hence, BTK plays a critical role in the activation of DDX41 helicase and STING signaling.

Rare earth metal complexes have special characteristics, such as extremely narrow emission bands and high internal quantum efficiencies, which are suitable to be used as the emission materials, chemistry and biological technology. Ternary nano complex of terbium gatifloxacin phenanthroline was synthesized.The composition and structure of ternary complex were characterized by element analysis, Mass Spectrometry (MS), UltraViolet Absorption Spectrometry (UV) and fluorescence spectra(FS). The influences of solubility, thermal stability and luminescent properties of complex as well as addition of phenanthroline secondary ligands on the fluorescence spectra of the ternary complexes were studied. The results of fluorescence spectra analysis showed that partial energy was transferred from Characterization to terbium ions by intramolecular energy transfer processes, meanwhile, the addition of phenanthroline can effectively increase the luminescence intensity of terbium icons. The complex possessed well luminescence and showed characteristic emission peaks of Tb3+ under UV light excitation and emitted strong green fluorescence. Moreover, in an ITO/PVK/Tb(GFLX)3Phen/Al device, Tb3+ ion can be excited by intramolecular ligand-to-metal energy transfer process. The main peak of emission at 545 nm is attributed to 5D0→7F2 transition of the Tb3+ ion, and this process results in the enhancing green emission. Biological actrivity properties of the rare earth complex was well studied.

n this paper, the ammonium dichromate and copper nitrate were used as raw materials to prepare the copper chromite, and nanocopper chromite as a catalyst was used to synthesize the monomer dioxanone in diethylene glycol dehydrogenation. Under the strict conditions of no water and no oxygen, the stannous octoate was selected to catalyze ring-opening polymerization of the dioxanone to prepare the polydioxanone. And dioxanone and its polymers were characterized with IR spectroscopy, 1H NMR spectroscopy, thermogravimetric analysis (TG) and differential scanning calorimetry (DSC ) measurements.

n this study, a pH/temperature sensitive polymeric hydrogel from poly (lysine methyl ester-diacetoxy tartaric acid) and sodium alginate (PLMD-SA) was prepared via the condensation polymerization. Using indomethacin as the model drug, the controlled drug-release from the resulting pH/temperature sensitive PLMD-SA was evaluated as functions of pH, PLMD content and temperature by UV spectrophotometer. It was found that the release amount of indomethacin in pH=7.4 phosphate buffer solution (PBS) was evidently higher than in pH=2.3 PBS.

In this paper, a new pH/temperature-sensitive beads with semi-interpenetrating polymeric network based on sodium alginate(SA) and poly(aspartic acid) derivatives(M-E-PSI) were prepared using as drug delivery carrier. With indomethacin as a drug model，we investigated the release behaviors of indomethacin in different pH value, temperature and ratio of SA/ M-E-PSI. It turned out that the release amount of indomethacin in pH=2.1 phosphate buffer solution(PBS) was evidently higher than that in pH=7.4 PBS. And also, the release amount of indomethacin was also increased with increasing temperature and poly(aspartic acid) derivatives content in the beads.

A novel pH-sensitive poly (2-(acryloyloxy) propanoic acid) hydrogel (PAPA) synthesized from lactic acid by radical polymerization has been investigated in this work. The structure of prepared monomer 2-(acryloyloxy) propanoic acid) (APA) has been characterized by FTIR and 1H-NMR measurements. PAPA hydrogel demonstrated an obvious pH sensitivity in its swelling in the range of 4-7 pH of phosphate buffer solution (PBS). The rapid response of the hydrogel makes it suitable for drug delivery application. Here, salicylic acid (SA) selected as a model drug, the in-vitro drug release as a function of pH and temperature was studied systematically. The cumulative release of salicylic acid reached up to 86.6% in pH=7.4 PBS at 37.0℃ within 550min. In pH=2.1 PBS, however, only 26.6% drug was released from the pH-sensitive PAPA on the same conditions.

In this study, a pH/temperature sensitive polymeric hydrogel from poly(N-acryloylglycine) and natural chitosan (PNAG-CS) was prepared via the radical polymerization. The effects of temperature and pH on the swelling behavior of PNAG-CS were systematically studied. Using caffeine as the model drug, the controlled caffeine-release from the resulting pH/temperature sensitive PNAG-CS was evaluated as functions of pH, polymer content and temperature by UV spectrophotometer.

In this paper, a new pH/temperature sensitive hydrogel bead (HME) with core-shelled structure as a drug delivery system was prepared using N-acryloylglycinate and sodium alginate. In caffeine release studies, the effect of different pH value, temperature and the polymer content were evaluated, respectively. The results showed that 62.2% drug was released from the sensitive beads in pH 2.1 within 300 min, whereas 99.3% drug diffused into the medium in pH 7.4 at 37℃. The significantly higher release was observed at higher temperature than at lower temperature. In addition the release amount of drug was decreased with increasing polymer content. The release behaviors of caffeine suggested a feasibility of the beads as pH/thermo-controlled drug release carrier.

In this paper, a new pH/temperature sensitive beads with core-shelled structure, composed of sodium alginate and poly(N-acryloylglycinate), were prepared using as drug delivery carrier. Selecting indomethacin as a model drug, in vitro drug release behaviors were investigated at different temperatures, phosphate buffer solutions (PBS) and polymer content. At pH=2.1, the release amount of indomethacin loaded in the beads was only 2.46% while this value approached to 95.23% in pH=7.4 PBS. In addition, the release rate of indomethacin at 37℃ is much higher than at 18℃.

A novel thermo-sensitive poly(N-acryloyl alanine methyl ester) (PAAME) was synthesized by radical polymerization. The structures of the corresponding monomer and polymer have been confirmed by 1H NMR and FTIR measurements. The thermo-sensitivity of PAAME was investigated by measuring their lower critical solution temperatures (LCST) in pure water and at different pH solution. The results indicated that PAAME exhibited a reversible thermo-sensibility in its aqueous solutions at 17.7 °C. The drug release study showed that 72% caffeine was released from hydrogel at 37 °C after 6 hours, while more than 94% caffeine was gradually diffused into the medium at 18 °C.

A novel jujube cake-like pH/temperature responsive hydrogel, as a drug delivery system, was prepared by two steps in this paper. The intelligent copolymer hydrogel (PME) was obtained from N-acryloylglycinate methyl ester (AGME) and N-acryloylglycinate ethyl ester (AGEE), using sodium laurate (SL) as an emulsifier and N, N '-methylenebisacrylamide (NMBA) as a crosslinking agent. Selecting indomethacin as a model drug, in vitro drug release behaviors were investigated at different temperatures, phosphate buffer solutions (PBS) and emulsifier content. The cumulative release of indomethacin from the pH/temperature sensitive hydrogel was apparently increased as the emulsifier content increased, the pH value increased and the temperature decreased. 48% indomethacin from the hydrogel PME was released in pH 7.4 PBS at 18 oC within 600 minutes, whereas only 17% indomethacin diffused into pH 2.1 PBS.

A series of pH/temperature sensitive hydrogel beads with semi-interpenetrating polymer network (semi-IPN), composed of sodium alginate and poly(N-acryloylglycinate) were prepared as drug delivery carrier. In pH=2.3 phosphate buffer solution (PBS), the release amount of indomethacin incorporated into the beads was about 9% within 610 min, while this value approached to 68% in pH=7.4 PBS. The release rate of indomethacin was higher at 37 than that at 20 . In addition, the release amount of indomethacin was increased with increasing poly(N-acryloylglycinate) content. These results suggest that the stimuli-sensitive beads have the potential to be used as an effective pH/temperature delivery system in bio-medical fields.

As a drug delivery carrier, a novel pH/temperature sensitive bead (pTSB) with core-shelled structure from poly(N-acryloylglycine) (PAG), copoly(N-acryloylglycine methyl este and N-acryloylglycine ethyl ester) was prepared by two steps. In pH=7.4 phosphate buffer solution (PBS), the cumulative release amount of indomethacin loaded in the pTSB was about 60.1 % within 500 mins, but this value only reached to 22.3 % in pH=2.1 PBS. The release behaviors of indomethacin from pTSB also exhibited a remarkable dependence on PAG content in the core. Additionally, the release rate of indomethacin was much faster at 18 oC than that at 37 oC due to the temperature sensitivity of poly(N-acryloylglycinates). The experimental results indicate that pTSB seems to have a potential application in the drug release system controlled via pH or temperature in the biomedical fields.

A highly ordered m-phenylenediimino-bridged ladder polyhydrosiloxane (abbr. OLPHS) with Mn=1.24×104 was synthesized under assistance of H-bonding template constructed from imino H-bonding, N(Si)-H⋯N(Si)-H, via a modified process of stoichiometric hydrolysis and dehydrochlorination condensation reaction between Si–Cl and Si–OH bonds. The complete ladder structure of OLPHS has been confirmed by the following three data. Two characteristic Bragg's peaks representing the ladder width (w=0.94nm) and ladder thickness (t=0.42nm) were observed in XRD analysis, which are consistent with those calculated by molecular simulation. The very sharp absorption with a small half-peak width (w1/2=0.5ppm) for [(–HN)HSiO2/2]n moiety of OLPHS in 29Si NMR spectrum indicated presence of the complete ladder structure. As collateral evidence, a higher glass transition temperature (Tg=105°C) is also recorded in the DSC measurement, implying the high stiffness of ladder chain of OLPHS.

Cell cycle progression is both regulated and accompanied by periodic changes in the expression levels of a large number of genes. To investigate cell cycle-regulated transcriptional programs in the fission yeast Schizosaccharomyces pombe, we developed a whole-genome oligonucleotide-based DNA microarray. Microarray analysis of both wild-type and cdc25 mutant cell cultures was performed to identify transcripts whose levels oscillated during the cell cycle. Using an unsupervised algorithm, we identified 747 genes that met the criteria for cell cycle-regulated expression. Peaks of gene expression were found to be distributed throughout the entire cell cycle. Furthermore, we found that four promoter motifs exhibited strong association with cell cycle phase-specific expression. Examination of the regulation of MCB motif-containing genes through the perturbation of DNA synthesis control/MCB-binding factor (DSC/MBF)-mediated transcription in arrested synchronous cdc10 mutant cell cultures revealed a subset of functional targets of the DSC/MBF transcription factor complex, as well as certain gene promoter requirements. Finally, we compared our data with those for the budding yeast Saccharomyces cerevisiae and found approximately 140 genes that are cell cycle regulated in both yeasts, suggesting that these genes may play an evolutionarily conserved role in regulation of cell cycle-specific processes. Our complete data sets are available at http://giscompute.gis.a-star.edu.sg/~gisljh/CDC.

EDSS is a comprehensive software system for water quality management in tidal river networks in general and for the Pearl River Delta in particular. Its purpose is to provide a practical tool that could assist government agencies in decision making for the efficient management of water resources in terms of both quantity and quality. By combining the capabilities of geographical information system (GIS), database management system (DBMS), model base management system (MBMS) and expert system, the aim is to improve the quality of decision making in what is becoming an increasingly complex area. This paper first outlines the basic concepts and philosophy adopted in developing EDSS, the system architecture, design features, implementation techniques and facilities provided. Thereafter, the core part of the system—the hydrodynamic and water quality models are described briefly. The final contribution in this paper describes the application of EDSS to the Pearl River Delta, which has the most complicated tidal river network patterns as well as the fastest economic development in the world. Examples are given of the real-world problems that can be addressed using the system, including cross-boundary water pollution analysis, regional drinking water take-up site selection, screening of important polluters, environmental impact assessment, and water quality zoning and planning. It is illustrated that EDSS can provide efficient and scientific analytical tools for planning and decision-making purposes in the information era.

The neuromedin B receptor (Nmbr) is an important physiological regulator of spontaneous activities and stress responses through different cascades as well as its autocrine and paracrine effects. Previous studies have revealed that neuromedin B (Nmb)and its receptor signal via the Rela(also known as p65)/Il6pathway in a mouse model of pregnancy. This study investigated the mechanism of Nmbrsignaling via the Rela/p65-Il6pathway and regulation of the concentration of intracellular free calcium ([Ca2+]i) during the onset of labor in primary mouse myometrial cell cultures isolated from mice in term labor. Data demonstrated Nmbragonist-mediated upregulation of the DNA binding activity of Rela/p65, Il6expression, and [Ca2+]iin a concentration-dependent manner. Furthermore, a significant correlation was observed between DNA binding activity of Rela/p65and Il6expression. Moreover, this up-regulation was blocked by Nmbrand Rela/p65knockdown, achieved by RNA interference (RNAi) technology. No significant differences were identified in the inhibition of Il6expression as a result of Nmbror Rela/p65knockdown. However, significant differences were observed between the [Ca2+]iin Rela/p65-specific group and that in the Nmbr-specific small interfering RNA (siRNA)-treated groups. These data demonstrated that the Nmb/Nmbrinteraction in pregnant myometrial primary cells in vitro predominantly influenced uterine activity through regulation of Il6expression via the Rela/p65pathway, although the effects of Nmbron [Ca2+]iinvolved several pathways that remain to be elucidated.