Programmable site-selective labeling of oligonucleotides based on carbene catalysis

Site-selective modification of oligonucleotides serves as an indispensable tool in many fields of research including research of fundamental biological processes, biotechnology, and nanotechnology. Here we report chemo- and regioselective modification of oligonucleotides based on rhodium(I)-carbene catalysis in a programmable fashion. Extensive screening identifies a rhodium(I)-catalyst that displays robust chemoselectivity toward base-unpaired guanosines in single and double-strand oligonucleotides with structurally complex secondary structures. Moreover, high regioselectivity among multiple guanosines in a substrate is achieved by introducing guanosine-bulge loops in a duplex. This approach allows the introduction of multiple unique functional handles in an iterative fashion, the utility of which is exemplified in DNA-protein cross-linking in cell lysates. The methods for investigation of DNA-binding proteins require site-selective chemical modifications to be introduced into oligonucleotides. Here, the authors report a chemo- and regioselective method for the modification of unpaired guanosines in single- and double-stranded oligonucleotides, based on Rh(I)-carbene catalysis

Husformer: A Multi-Modal Transformer for Multi-Modal Human State Recognition

Human state recognition is a critical topic with pervasive and important applications in human-machine systems.Multi-modal fusion, the combination of metrics from multiple data sources, has been shown as a sound method for improving the recognition performance. However, while promising results have been reported by recent multi-modal-based models, they generally fail to leverage the sophisticated fusion strategies that would model sufficient cross-modal interactions when producing the fusion representation; instead, current methods rely on lengthy and inconsistent data preprocessing and feature crafting. To address this limitation, we propose an end-to-end multi-modal transformer framework for multi-modal human state recognition called Husformer.Specifically, we propose to use cross-modal transformers, which inspire one modality to reinforce itself through directly attending to latent relevance revealed in other modalities, to fuse different modalities while ensuring sufficient awareness of the cross-modal interactions introduced. Subsequently, we utilize a self-attention transformer to further prioritize contextual information in the fusion representation. Using two such attention mechanisms enables effective and adaptive adjustments to noise and interruptions in multi-modal signals during the fusion process and in relation to high-level features. Extensive experiments on two human emotion corpora (DEAP and WESAD) and two cognitive workload datasets (MOCAS and CogLoad) demonstrate that in the recognition of human state, our Husformer outperforms both state-of-the-art multi-modal baselines and the use of a single modality by a large margin, especially when dealing with raw multi-modal signals. We also conducted an ablation study to show the benefits of each component in Husformer

Resistin enhances the expansion of regulatory T cells through modulation of dendritic cells

<p>Abstract</p> <p>Background</p> <p>Resistin, a member of adipokine family, is known to be involved in the modulation of immune responses including inflammatory activity. Interestingly, resistin is secreted by adipocytes in mice and rats whereas it is secreted by leukocytes in humans. However, the mechanism behind the effect of resistin on the expansion of regulatory T cells (Tregs) remains poorly understood. Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs.</p> <p>Results</p> <p>Both protein and mRNA expression of <it>FoxP3</it>, a representative marker of Tregs, increased in a dose-dependent manner when peripheral blood mononuclear cells were treated with resistin. At the same time, resistin had no direct effect on the induction of <it>FoxP3 </it>in CD4⁺T cells, suggesting an indirect role through other cells type(s). Since DCs are an important player in the differentiation of T cells, we focused on the role of DCs in the modulation of Tregs by resistin. Resistin suppressed the expression of interferon regulatory factor (IRF)-1 and its target cytokines, IL-6, IL-23p19 and IL-12p40, in DCs. Furthermore, <it>FoxP3 </it>expression is increased in CD4⁺T cells when co-cultured with DCs and concomitantly treated with resistin.</p> <p>Conclusion</p> <p>Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.</p

Recombinant TAT–gelonin fusion toxin: Synthesis and characterization of heparin/protamine‐regulated cell transduction

Protein toxins, such as gelonin, are highly desirable anti‐cancer drug candidates due to their unparalleled potency and repetitive reaction mechanism in inhibiting protein translation. However, for its potential application in cancer therapy, there remains the cell membrane barrier that allows permeation of only small molecules, which must be overcome. To address this challenge, we conjugated gelonin with a protein transduction domain (PTD), the TAT peptide, via genetic recombination. The chimeric TAT–gelonin fusion protein (TAT‐Gel) retained equipotent N ‐glycosidase activity yet displayed greater cell uptake than unmodified recombinant gelonin (rGel), thereby yielding a significantly augmented cytotoxic activity. Remarkably, TAT‐Gel displayed up to 177‐fold lower IC 50 (avg. 54.3 n M ) than rGel (avg. IC 50 : 3640 n M ) in tested cell lines. This enhanced cytotoxicity, however, also raised potential toxicity concerns due to the non‐selectivity of PTD in its mediated cell transduction. To solve this problem, we investigated the plausibility of regulating the cell transduction of TAT‐Gel via a reversible masking using heparin and protamine. Here, we demonstrated, both in vitro and in vivo , that the cell transduction of TAT‐Gel can be completely curbed with heparin and yet this heparin block can be efficiently reversed by the addition of protamine. This reversible tight regulation of the cell transduction of TAT‐Gel by heparin and protamine sheds light of possible application of TAT‐Gel in achieving a highly effective yet safe drug therapy for the treatment of tumors. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 409–419, 2015.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109572/1/jbma35188.pd

Soft lithography for microfluidics: a review

Soft lithography has provided a low-expertise route toward micro/nanofabrication and is playing an important role in microfluidics, ranging from simple channel fabrication to the creation of micropatterns onto a surface or within a microfluidic channel. In this review, the materials, methods, and applications of soft lithography for microfluidics are briefly summarized with a particular emphasis on integrated microfluidic systems containing physical microstructures or a topographically patterned substrate. Relevant exemplary works based on the combination of various soft lithographic methods using microfluidics are introduced with some comments on their merits and weaknesses.This work was supported by Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R01-2007-000- 20675-0) and the Grant-in-Aid for Next-Generation New Technology Development Programs from the Korea Ministry of Commerce, Industry and Energy (No.10030046). This work was also supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund)(KRF-2007-331-D00064) for Sun Min Kim

Effectiveness of the Novel Herbal Medicine, KIOM-MA, and Its Bioconversion Product, KIOM-MA128, on the Treatment of Atopic Dermatitis

This study was conducted to determine if oral administration of the novel herbal medicine, KIOM-MA, and its Lactobacillus acidophilus-fermented product, KIOM-MA128, has therapeutic properties for the treatment of atopic dermatitis (AD). Using AD-induced BALB/c mice by Ovalbumin and aluminum hydroxide, the effectiveness of KIOM-MA and KIOM-MA128 on AD was evaluated. Oral administration of KIOM-MA and KIOM-MA128 reduced major clinical signs of AD including erythema/darkening, edema/papulation, excoriations, lichenification/prurigo, and dryness. Interestingly, KIOM-MA128 more significantly improved AD-related symptoms including decrease of IgE level in the plasma as well as reduction of scratching behavior, skin severity in the AD BALB/c model. HPLC analysis showed the significant changes in the constituent patterns between KIOM-MA and KIOM-MA128. Our results suggest that both KIOM-MA and KIOM-MA128 have potential for therapeutic reagent for the treatment of AD, and further, the efficacy is significantly enhanced by L. acidophilus fermentation via increases in its indicator molecule

Kinetic roughening of ion-sputtered Pd(001) surface: Beyond the Kuramoto-Sivashinsky model

The kinetic roughening of Ar+ ion-sputtered Pd(001) surface was investigated. The facet formation on the sputtered surface was studied by tracing the extradiffraction peaks or satellites around the diffraction peaks corresponding to the sample surface. The morphological evolution of the sputtered Pd(001) surface was also investigated by an scanning tunneling microscopy (STM). It was shown that the nanoscale adatom islands form and grow with increasing sputter time.open313