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Heterogeneity in the etiopathology of autism spectrum disorders (ASD) limits the development of generic remedies, requires individualistic and patient-specific research. Recent progress in human-induced pluripotent stem cell (iPSC) technology provides a novel platform for modeling ASDs for studying complex neuronal phenotypes. In this study, we generated telencephalic induced neuronal (iN) cells from iPSCs derived from an ASD patient with a heterozygous point mutation in the DSCAMgene. The mRNA of DSCAM and the density of DSCAM in dendrites were significantly decreased in ASD compared to control iN cells. RNA sequencing analysis revealed that several synaptic function-related genes including NMDA receptor subunits were downregulated in ASD iN cells. Moreover, NMDA receptor (R)-mediated currents were significantly reduced in ASD compared to control iN cells. Normal NMDA-R-mediated current levels were rescued by expressing wild-type DSCAM in ASD iN cells, and reduced currents were observed by truncated DSCAM expression in control iN cells. shRNA-mediated DSCAM knockdown in control iN cells resulted in the downregulation of an NMDA-R subunit, which was rescued by the overexpression of shRNA-resistant DSCAM. Furthermore, DSCAM was co-localized with NMDA-R components in the dendritic spines of iN cells whereas their co-localizations were significantly reduced in ASD iN cells. Levels of phospho-ERK1/2 were significantly lower in ASD iN cells, suggesting a potential mechanism. A neural stem cell-specific Dscamheterozygous knockout mouse model, showing deficits in social interaction and social memory with reduced NMDA-R currents. These data suggest that DSCAMmutation causes pathological symptoms of ASD by dysregulating NMDA-R function.

Establishing a platform for the bioconversion of waste resources into value-added compounds is critical for achieving a sustainable and eco-friendly economy. Herein, we produced polyhydroxyalkanoate via microbial fermentation using cabbage waste as a feedstock and metabolically engineered Escherichia coli. For this, the hydrolysis conditions of cabbage waste were optimized by focusing on parameters such as substrate and enzyme concentrations to enhance the saccharification efficiency. The phaABCoperon, which encodes key enzymes responsible for polyhydroxyalkanoate biosynthesis in Ralstonia eutrophaH16, was overexpressed in E. coli. Using cabbage hydrolysate as the feedstock, this engineered E. colistrain could produce poly(3-hydroxybutyrate) with a polymer content of 26.0 wt % of dry cell weight. Moreover, malic acid in cabbage hydrolysate significantly enhanced poly(3-hydroxybutyrate) production; the addition of 0.5 g/L malic acid markedly increased poly(3-hydroxybutyrate) content by 59.9%. This study demonstrates the potential of cabbage waste as a promising raw material for the microbial production of polyhydroxyalkanoate.

ABSTRACTAccording to the previously described anti-photoaging effect of the enzyme-processed Panax ginsengextract and Gastrodia elataextract, we hypothesized that the combination of the two extracts would have superior effect to protect human skin from UVB radiation. Besides, the mixture of active components isolated from herbal extracts, ginsenoside F2, and α-gastrodin was investigated on the photo-protective capability. The expression of aging-related markers including matrix metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), and procollagen type 1 was evaluated using ELISA kits. It was reported that the herbal extract at a Panax ginsengextract to Gastrodia elataextract ratio of 1:10 (w/w) and the compound mixture with equal proportion of ginsenoside F2 and α-gastrodin exhibited significant inhibition of MMP-1 and IL-6 production, and marked upregulation of procollagen type 1 formation. Thus, the combination of either the enzyme-processed herbal extracts or their active components would enhance the properties of prevention and treatment of UVB-induced skin damage.

Developing a highly efficient and ecofriendly system to produce desired products from waste can be considered important to a sustainable society. Here, we report for the first time high-yield production of lycopene through metabolically engineering an extremophilic microorganism, Deinococcus radioduransR1, from corn steep liquor (CSL) and glycerol. First, the crtLmgene-encoding lycopene cyclase was deleted to prevent the conversion of lycopene to γ-carotene. Then, the crtBgene-encoding phytoene synthase and the dxsgene-encoding 1-deoxy-d-xylulose 5-phosphate synthase were overexpressed to increase carbon flux toward lycopene. The engineered ΔcrtLm/crtB+dxs+D. radioduransR1 could produce 273.8 mg/L [80.7 mg/g dry cell weight (DCW)] and 373.5 mg/L (108.0 mg/g DCW) of lycopene from 10 g/L of glucose with 5 g/L of yeast extract and 9.9 g/L of glucose with 20 g/L of CSL, respectively. Moreover, the lycopene titer and content were increased by 26% (470.6 mg/L) and 28% (138.2 mg/g DCW), respectively, when the carbon source was changed to glycerol. Finally, fed-batch fermentation of the final engineered strain allowed the production of 722.2 mg/L (203.5 mg/g DCW) of lycopene with a yield and productivity of 20.3 mg/g glycerol and 6.0 mg/L/h, respectively, from 25 g/L of CSL and 35.7 g/L of glycerol.

In metabolic engineering, predicting gene overexpression targets remains challenging because both endogenous and heterologous genes in a large metabolic space can be candidates, in contrast to gene knockout targets that are confined to endogenous genes. We report the development of iBridge that identifies positive and negative metabolites exerting positive and negative impacts on product formation, respectively, based on the sum of covariances of their outgoing (consuming) reaction fluxes for a target chemical. Then, “bridge” reactions converting negative metabolites to positive metabolites are identified as overexpression targets, while the opposites as downregulation targets. Using iBridge, overexpression and downregulation targets are suggested for the production of 298 chemicals and validated for 36 chemicals experimentally demonstrated in previous studies. Finally, iBridge is employed to engineer Escherichia colistrains capable of producing 10.3 g/L of D-panthenol, a compound not previously produced, as well as putrescine and 4-hydroxyphenyllactate at enhanced titers, 63.7 and 8.3 g/L, respectively.

The efficient treatment of radioactive waste arising from nuclear accidents and overuse of radioisotopes has become an important issue, and much effort has been devoted to protecting the environment from such toxic radioactive materials. Among them, radioactive iodine in water is regarded as one of the most palpable threats to humans, as it is generated by post-use in medical and industrial applications. Although a few adsorbents and purification processes have been reported, the development of a better desalination method that is able to provide high removal efficiency, ion-selectivity, and reusability is still in demand. Herein, we report a hybrid composite membrane, composed of gold nanoparticles and cellulose acetate membranes, which has the potential to be used for efficient desalination of radioactive iodine. A single filtration process using this membrane provided high removal efficiency with more than two orders of magnitude iodide anion removal within a minute and excellent ion-selectivity. Moreover, the same operation can be applied several times without significant decrease of its performance. Therefore, it is anticipated that our work will be a new avenue for desalination of radioactive iodine in various aqueous media.

ABSTRACTTIGIT is an immune checkpoint receptor that is expressed on subsets of activated T cells and natural killer (NK) cells. Several ligands for TIGIT, including poliovirus receptor (PVR), are expressed on cancer cells and mediate inhibitory signaling to suppress antitumor activities of the immune cells. Many studies support that the TIGIT signaling is a potential target for cancer immunotherapy. We developed an IgG4-type monoclonal antibody against human TIGIT, designated as MG1131, using a phage display library of single-chain variable fragments (scFvs). MG1131 interacts with TIGIT much more tightly than PVR does. The crystal structure of a scFv version of MG1131 bound to TIGIT was determined, showing that MG1131 could block the PVR-TIGIT interaction and thus the immunosuppressive signaling of TIGIT. Consistently, MG1131 is bound to TIGIT-expressing cells and interferes with PVR binding to these cells. Moreover, MG1131 increased NK cell-mediated tumor killing activities, inhibited immunosuppressive activity of regulatory T (Treg) cells from healthy donors, and restored interferon-γ secretion from peripheral blood mononuclear cells derived from multiple myeloma patients. MG1131 also increased T cell infiltration to the tumor site and inhibited tumor growth in mice. Collectively, these data indicate that MG1131 modulates the effector functions of T cells and NK cells positively and Treg cells negatively.

A new ABA-type triblock copolymer was synthesized by coupling reaction of anhydride and amine-functionalized telechelic polymers. The two blocks of the copolymer, polystyrene end-functionalized with anhydride group (PS-anh) and poly(arylene ether sulfone) functionalized with aromatic amine groups at the termini (PAES-amn), were synthesized by living anionic and condensation polymerization, respectively. The block copolymer was characterized by size exclusion chromatography (SEC), thermal (DSC and TGA) studies, and the morphology investigated by atomic force microscopy (AFM) and transmission electron microscopy (TEM). The microstructure of the block copolymer was affected by the volume fraction of the constituent blocks.

Two series of waterborne polyurethane–urea anionomers were prepared by a polyaddition reaction with isophorone diisocyanate, poly(tetramethylene oxide) glycol (weight-average molecular weight = 1000), dimethylol propionic acid (DMPA), and ethylene diamine as chain extenders. Triethylamine (TEA) or 28:1 mol/mol ammonium hydroxide (NH4OH)/cupric hydroxide [Cu(OH)2] was used as a neutralization agent [NH(C2H5)3⁺ or NH4⁺/Cu²⁺ counterion] for the pendant COOH group of DMPA. The effects of the degree of neutralization and counterion on the particle size of the dispersions, the conductivity, and the antibacterial and mechanical properties of polyurethane–urea anionomer films were investigated. The particle sizes of the two sample series dispersions decreased with an increasing degree of neutralization. Aqueous dispersions of polyurethane–urea anionomers with particle sizes of 30–120 nm were stable for about 3 months. By infrared spectroscopy, it was found that TEA-based samples (T series) had higher fractions of hydrogen-bonded carbonyl groups in the ordered region than NH4OH/Cu(OH)2-based samples (S series). However, the fractions of hydrogen-bonded carbonyl groups in the disordered region of the S-series samples were higher than those of the T-series samples. The conductivities of the S-series film samples were higher than those of the T-series samples. However, the T-series film samples commonly had higher tensile strengths and initial moduli than the S-series samples. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2375–2383, 2002

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.