Integrated proteomic and genomic analysis to identify predictive biomarkers for valproate response in bipolar disorder: a 6-month follow-up study.

BACKGROUND: Several genetic studies have been undertaken to elucidate the intricate interplay between genetics and drug responses in bipolar disorder (BD). However, there has been notably limited research on biomarkers specifically linked to valproate, with only a few studies investigating integrated proteomic and genomic factors in response to valproate treatment. Therefore, this study aimed to identify biological markers for the therapeutic response to valproate treatment in BD. Patients with BD in remission were assessed only at baseline, whereas those experiencing acute mood episodes were evaluated at three points (baseline, 8 ± 2 weeks, and 6 ± 1 months). The response to valproate treatment was measured using the Alda scale, with individuals scoring an Alda A score ≥ 5 categorized into the acute-valproate responder (acute-VPAR) group. We analyzed 158 peptides (92 proteins) from peripheral blood samples using multiple reaction monitoring mass spectrometry, and proteomic result-guided candidate gene association analyses, with 1,627 single nucleotide variants (SNVs), were performed using the Korean chip. RESULTS: The markers of 37 peptides (27 protein) showed temporal upregulation, indicating possible association with response to valproate treatment. A total of 58 SNVs in 22 genes and 37 SNVs in 16 genes showed nominally significant associations with the Alda A continuous score and the acute-VPAR group, respectively. No SNVs reached the genome-wide significance threshold; however, three SNVs (rs115788299, rs11563197, and rs117669164) in the secreted phosphoprotein 2 gene reached a gene-based false discovery rate-corrected significance threshold with response to valproate treatment. Significant markers were associated with the pathophysiological processes of bipolar disorders, including the immune response, acute phase reaction, and coagulation cascade. These results suggest that valproate effectively suppresses mechanisms associated with disease progression. CONCLUSIONS: The markers identified in this study could be valuable indicators of the underlying mechanisms associated with response to valproate treatment.

Wafer-Scale Integration of Highly Uniform and Scalable MoS2 Transistors.

Molybdenum disulfide with atomic-scale flatness has application potential in high-speed and low-power logic devices owing to its scalability and intrinsic high mobility. However, to realize viable technologies based on two-dimensional materials, techniques that enable their large-area growth with high quality and uniformity on wafer cale is a prerequisite. Here, we provide a route toward highly uniform growth of a wafer-scale, four-layered MoS2 film on a 2 in. substrate via a sequential process consisting of the deposition of a molybdenum trioxide precursor film by sputtering followed by postsulfurization using a chemical vapor deposition process. Spatial spectroscopic analyses by Raman and PL mapping validated that the as-synthesized MoS2 thin films exhibit high uniformity on a 2 in. sapphire substrate. The highly uniform MoS2 layers allow a successful integration of devices based on ∼1200 MoS2 transistor arrays with a yield of 95% because of their extreme homogeneity on Si wafers. Moreover, a pulse electrical measurement technique enabled investigation of the inherent physical properties of the atomically thin MoS2 layers by minimizing the charge-trapping effect. Such a facile synthesis method can be possibly applied to other 2D transition metal dichalcogenides to ultimately realize the chip integration of device architectures with all 2D-layered building blocks.

Alloyed 2D Metal-Semiconductor Heterojunctions: Origin of Interface States Reduction and Schottky Barrier Lowering.

The long-term stability and superior device reliability through the use of delicately designed metal contacts with two-dimensional (2D) atomic-scale semiconductors are considered one of the critical issues related to practical 2D-based electronic components. Here, we investigate the origin of the improved contact properties of alloyed 2D metal-semiconductor heterojunctions. 2D WSe2-based transistors with mixed transition layers containing van der Waals (M-vdW, NbSe2/WxNb1-xSe2/WSe2) junctions realize atomically sharp interfaces, exhibiting long hot-carrier lifetimes of approximately 75,296 s (78 times longer than that of metal-semiconductor, Pd/WSe2 junctions). Such dramatic lifetime enhancement in M-vdW-junctioned devices is attributed to the synergistic effects arising from the significant reduction in the number of defects and the Schottky barrier lowering at the interface. Formation of a controllable mixed-composition alloyed layer on the 2D active channel would be a breakthrough approach to maximize the electrical reliability of 2D nanomaterial-based electronic applications.

N-Terminal Acetylation-Targeted N-End Rule Proteolytic System: The Ac/N-End Rule Pathway.

Although Nα-terminal acetylation (Nt-acetylation) is a pervasive protein modification in eukaryotes, its general functions in a majority of proteins are poorly understood. In 2010, it was discovered that Nt-acetylation creates a specific protein degradation signal that is targeted by a new class of the N-end rule proteolytic system, called the Ac/N-end rule pathway. Here, we review recent advances in our understanding of the mechanism and biological functions of the Ac/N-end rule pathway, and its crosstalk with the Arg/N-end rule pathway (the classical N-end rule pathway).

Flexible Textile-Based Organic Transistors Using Graphene/Ag Nanoparticle Electrode.

Highly flexible and electrically-conductive multifunctional textiles are desirable for use in wearable electronic applications. In this study, we fabricated multifunctional textile composites by vacuum filtration and wet-transfer of graphene oxide films on a flexible polyethylene terephthalate (PET) textile in association with embedding Ag nanoparticles (AgNPs) to improve the electrical conductivity. A flexible organic transistor can be developed by direct transfer of a dielectric/semiconducting double layer on the graphene/AgNP textile composite, where the textile composite was used as both flexible substrate and conductive gate electrode. The thermal treatment of a textile-based transistor enhanced the electrical performance (mobility = 7.2 cm²·V-1·s-1, on/off current ratio = 4 × 105, and threshold voltage = -1.1 V) due to the improvement of interfacial properties between the conductive textile electrode and the ion-gel dielectric layer. Furthermore, the textile transistors exhibited highly stable device performance under extended bending conditions (with a bending radius down to 3 mm and repeated tests over 1000 cycles). We believe that our simple methods for the fabrication of graphene/AgNP textile composite for use in textile-type transistors can potentially be applied to the development of flexible large-area electronic clothes.

Highly Conductive Graphene/Ag Hybrid Fibers for Flexible Fiber-Type Transistors.

Mechanically robust, flexible, and electrically conductive textiles are highly suitable for use in wearable electronic applications. In this study, highly conductive and flexible graphene/Ag hybrid fibers were prepared and used as electrodes for planar and fiber-type transistors. The graphene/Ag hybrid fibers were fabricated by the wet-spinning/drawing of giant graphene oxide and subsequent functionalization with Ag nanoparticles. The graphene/Ag hybrid fibers exhibited record-high electrical conductivity of up to 15,800 S cm(-1). As the graphene/Ag hybrid fibers can be easily cut and placed onto flexible substrates by simply gluing or stitching, ion gel-gated planar transistors were fabricated by using the hybrid fibers as source, drain, and gate electrodes. Finally, fiber-type transistors were constructed by embedding the graphene/Ag hybrid fiber electrodes onto conventional polyurethane monofilaments, which exhibited excellent flexibility (highly bendable and rollable properties), high electrical performance (µh = 15.6 cm(2) V(-1) s(-1), Ion/Ioff > 10(4)), and outstanding device performance stability (stable after 1,000 cycles of bending tests and being exposed for 30 days to ambient conditions). We believe that our simple methods for the fabrication of graphene/Ag hybrid fiber electrodes for use in fiber-type transistors can potentially be applied to the development all-organic wearable devices.

Synthetic lethal screen of NAA20, a catalytic subunit gene of NatB N-terminal acetylase in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae NatB N-terminal acetylase contains a catalytic subunit Naa20 and an auxiliary subunit Naa25. To elucidate the cellular functions of the NatB, we utilized the Synthetic Genetic Array to screen for genes that are essential for cell growth in the absence of NAA20. The genome-wide synthetic lethal screen of NAA20 identified genes encoding for serine/threonine protein kinase Vps15, 1,3-beta-glucanosyltransferase Gas5, and a catabolic repression regulator Mig3. The present study suggests that the catalytic activity of the NatB N-terminal aceytase is involved in vacuolar protein sorting and cell wall maintenance.

The Relationship between Life Style, Menstrual Attitude and Premenstrual Syndrome in Nursing Students.

PURPOSE: The purpose of this study was to identify the relationships between life style, menstrual attitude and premenstrual syndrome in nursing students. METHODS: The study participants were 246 nursing students of a university in Gyeunggi province. Data were collected by a self-administered questionnaire from May to June, 2012. Collected data were analyzed using the SPSS/WIN 20.0 program with descriptive statistics, Pearson correlation coefficient, t-test, one-way ANOVA and Scheffe test. RESULTS: Students who had undesirable alcohol habits (r=.15, p=.020) and negative menstrual attitude (r=.17, p=.009) experienced more a severe premenstrual syndrome (PMS). Students with dysmenorrhea had more severe PMS (F=12.41, p<.001) and a negative menstrual attitude (F=6.18, p<.001). CONCLUSION: These finding suggest that PMS would be alleviated by nursing interventions to improve alcohol habits and decrease negative menstrual attitudes, and nursing interventions for dysmenorrhea would be helpful in PMS management in nursing students. Further studies on the development of nursing interventions related to these factors are needed for PMS management.

Nitrated fatty acids prevent TNFalpha-stimulated inflammatory and atherogenic responses in endothelial cells.

Nitration products (nitroalkenes) of linoleic acid (LNO(2)) and oleic acid (OA-NO(2)) can act as endogenous PPARgamma ligands with electrophilic properties to exert anti-inflammatory effects on atherosclerotic plaques in the vasculature. Here, we show that OA-NO(2) and LNO(2) prevent tumor necrosis factor alpha (TNFalpha)-stimulated inflammatory and atherogenic responses in human umbilical vein endothelial cells (HUVECs). Both OA-NO(2) and LNO(2) prevented TNFalpha-stimulated release of the cytokines, IL-6, IL-8, IL-12/p40, IFNgamma, MCP-1, and IP-10, and inhibited NF-kappaB activation. OA-NO(2) and LNO(2) also blocked TNFalpha-induced expression of the adhesion molecules, ICAM-1, VCAM-1, and E-selectin, and suppressed monocyte adhesion to HUVECs. In each case, OA-NO(2) was more potent and efficacious than was LNO(2), possibly due to increased stability in aqueous media. Collectively, these results substantiate a new functional role for nitrated fatty acids, demonstrating that OA-NO(2) and LNO(2) exert an anti-inflammatory function against the inflammatory cascade initiated by the representative pro-inflammatory cytokine, TNFalpha.

Induction of IL-10-producing CD4+CD25+ T cells in animal model of collagen-induced arthritis by oral administration of type II collagen.

Induction of oral tolerance has long been considered a promising approach to the treatment of chronic autoimmune diseases, including rheumatoid arthritis (RA). Oral administration of type II collagen (CII) has been proven to improve signs and symptoms in RA patients without troublesome toxicity. To investigate the mechanism of immune suppression mediated by orally administered antigen, we examined changes in serum IgG subtypes and T-cell proliferative responses to CII, and generation of IL-10-producing CD4+CD25+ T-cell subsets in an animal model of collagen-induced arthritis (CIA). We found that joint inflammation in CIA mice peaked at 5 weeks after primary immunization with CII, which was significantly less in mice tolerized by repeated oral feeding of CII before CIA induction. Mice that had been fed with CII also exhibited increased serum IgG1 and decreased serum IgG2a as compared with nontolerized CIA animals. The T-cell proliferative response to CII was suppressed in lymph nodes of tolerized mice also. Production of IL-10 and of transforming growth factor-beta from mononuclear lymphocytes was increased in the tolerized animals, and CD4+ T cells isolated from tolerized mice did not respond with induction of IFN-gamma when stimulated in vitro with CII. We also observed greater induction of IL-10-producing CD4+CD25+ subsets among CII-stimulated splenic T cells from tolerized mice. These data suggest that when these IL-10-producing CD4+CD25+ T cells encounter CII antigen in affected joints they become activated to exert an anti-inflammatory effect.