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Invasive candidiasis has high mortality rates in immunocompromised patients, causing serious health problems. In mouse models, innate immunity protects the host by rapidly mobilizing a variety of resistance and tolerance mechanisms to systemic Candida albicans infection. We have previously demonstrated that exogenous IL-33 regulates multiple steps of innate immunity involving resistance and tolerance processes. In this study, we systematically analyzed the in vivo functions of endogenous IL-33 using Il33−/− mice and in vitro immune cell culture. Tubular epithelial cells mainly secreted IL-33 in response to systemic C. albicans infection. Il33−/− mice showed increased mortality and morbidity, which were due to impaired fungal clearance. IL-33 initiated an innate defense mechanism by costimulating dendritic cells to produce IL-23 after systemic C. albicans infection, which in turn promoted the phagocytosis of neutrophils through secretion of GM-CSF by NK cells. The susceptibility of Il33−/− mice was also associated with increased levels of IL-10, and neutralization of IL-10 resulted in enhanced fungal clearance in Il33−/− mice. However, depletion of IL-10 overrode the effect of IL-33 on fungal clearance. In Il10−/− mouse kidneys, MHC class II+F4/80+ macrophages were massively differentiated after C. albicans infection, and these cells were superior to MHC class II−F4/80+ macrophages that were preferentially differentiated in wild-type mouse kidneys in killing of extracellular hyphal C. albicans. Taken together, our results identify IL-33 as critical early regulator controlling a serial downstream signaling events of innate defense to C. albicans infection.

Despite advances in therapeutic strategies for multiple sclerosis (MS), the therapy options remain limited with various adverse effects. Here, the therapeutic potential of CKD-506, a novel HDAC6-selective inhibitor, against MS was evaluated in mice with myelin oligodendrocyte glycoprotein35–55 (MOG35–55)-induced experimental autoimmune encephalitis (EAE) under various treatment regimens. CKD-506 exerted prophylactic and therapeutic effects by regulating peripheral immune responses and maintaining blood–brain barrier (BBB) integrity. In MOG35–55-re-stimulated splenocytes, CKD-506 decreased proliferation and downregulated the expression of IFN-γ and IL-17A. CKD-506 downregulated the levels of pro-inflammatory cytokines in the blood of EAE mice. Additionally, CKD-506 decreased the leakage of intravenously administered Evans blue into the spinal cord; CD4+ T cells and CD4−CD11b+CD45+ macrophage/microglia in the spinal cord was also decreased. Moreover, CKD-506 exhibited therapeutic efficacy against MS, even when drug administration was discontinued from day 15 post-EAE induction. Disease exacerbation was not observed when fingolimod was changed to CKD-506 from day 15 post-EAE induction. CKD-506 alleviated depression-like behavior at the pre-symptomatic stage of EAE. In conclusion, CKD-506 exerts therapeutic effects by regulating T cell- and macrophage-mediated peripheral immune responses and strengthening BBB integrity. Our results suggest that CKD-506 is a potential therapeutic agent for MS.

제안하는 애플리케이션은 한국 교육과정에서 가장 먼저 영어를 접하는 초등학생들을 대상으로, 영어 학습에 대한 지속적인 흥미와 자신감을 기르는 것을 목표로 한다. 주요 기능에는 영어 동화 읽어 주기, 영어 단어 및 문장 퀴즈, 영어 발음 테스트, 사물 인식을 통한 일상 생활에서의 영어 학습 등이 있다. 주요 기능들은 딥신경망 모델로 학습된 자연언어처리 기술을 활용하여 완성도를 높였으며, 특히 사물 인식 단어장에서는 기존 모델에 수천 장의 이미지들을 직접 학습시켜 정밀 튜닝된 모델을 이용하여 일상생활속의 물체들에 대해 높은 인식률을 확보했다. 영어를 이해하고 표현하는 능력은 필수적이지만 학교 밖에서 영어를 접할 기회가 매우 제한되어 있는 우리나라에서 본 작품을 통해 다양한 멀티미디어 자료와 지속적인 영어 사용 기회를 제공하고자 한다.

Although tofacitinib has shown highly significant efficacy for rheumatoid arthritis (RA), there are still a considerable number of patients that are non-responders owing to its limited effectiveness and various adverse effects. Thus, alternative options with better efficacy and lower toxicity are desired. Here, M-134, a recently developed HDAC6 inhibitor, was examined for its therapeutic potential when combined with tofacitinib in a rat model of RA. The single or combined administration of M-134 and tofacitinib was examined in complete Freund’s adjuvant-induced arthritis (AIA) or collagen-induced arthritis (CIA) rodent models. To evaluate the therapeutic and adverse effects, the following factors were observed: macroscopic or microscopic scoring of all four paws; the expression of ICAM-1, VCAM-1, and IP-10 in the joints and that of various cytokines and chemokines in the plasma; the weight of the thymus and the liver; and changes in hematological enzymes. Combination treatment showed strong synergistic effects as measured by the clinical score and histological changes, without adverse effects such as weight loss in the thymus and increased liver enzymes (ALT and AST). Additionally, it also reduced ICAM-1, VCAM-1, and IP-10 expression in the joints, and M-134 increased the efficacy of tofacitinib by regulating various cytokines, such as interleukin (IL)-1β, IL-17, and TNF-α, in the serum of AIA rats. Differences in the cytokine expression for each drug were found in the CIA model. M-134 and tofacitinib combination therapy is a potential option for the treatment of RA through the regulation of cytokines, chemokines, and adhesion molecules.

Spinal muscular atrophy (SMA) is caused by homozygous survival of motor neurons 1 (SMN1) gene deletion, leaving a duplicate gene, SMN2, as the sole source of SMN protein. However, a defect in SMN2 splicing, involving exon 7 skipping, results in a low level of functional SMN protein. Therefore, the upregulation of SMN protein expression from the SMN2 gene is generally considered to be one of the best therapeutic strategies to treat SMA. Most of the SMA drug discovery is based on synthetic compounds, and very few natural compounds have been explored thus far. Here, we performed an unbiased mechanism-independent and image-based screen of a library of microbial metabolites in SMA fibroblasts using an SMN-specific immunoassay. In doing so, we identified brefeldin A (BFA), a well-known inhibitor of ER-Golgi protein trafficking, as a strong inducer of SMN protein. The profound increase in SMN protein was attributed to, in part, the rescue of the SMN2 pre-mRNA splicing defect. Intriguingly, BFA increased the intracellular calcium concentration, and the BFA-induced exon 7 inclusion of SMN2 splicing, was abrogated by the depletion of intracellular calcium and by the pharmacological inhibition of calcium/calmodulin-dependent kinases (CaMKs). Moreover, BFA considerably reduced the expression of Tra2-β and SRSF9 proteins in SMA fibroblasts and enhanced the binding of PSF and hnRNP M to an exonic splicing enhancer (ESE) of exon 7. Together, our results demonstrate a significant role for calcium and its signaling on the regulation of SMN splicing, probably through modulating the expression/activity of splicing factors.

The Korean Obesity Index, which contains standard reference data (SRD) of obesity, was established in 2016 and revised in 2017 based on national health screening data to provide the distribution of the body mass index (BMI) of the whole population of Korea as a reference. This study aimed to investigate the effect of the SRD of obesity on the incidence of hypertension (HTN) and diabetes mellitus (DM).The percentile of BMI was calculated for each of the 864 subgroups by defined by gender, region, and age group according to the groupings in the SRD. Incident cases were defined as the presence of HTN and DM and medication prescription in the health care utilization database for a given individual in 2017, but not in 2015-2016. Logistic regression for the incidence of HTN and DM according to the relative distribution of BMI was performed. Gender, age, insurance type, insurance contribution, smoking, drinking, physical activity, blood pressure, waist circumference, fasting glucose, triglycerides, high-density lipoprotein cholesterol, the Charlson comorbidity index (2012-2014), and diagnosis and medication for HTN and DM (2015-2017) were adjusted in the analysis.The C-statistics of the fully adjusted model for HTN and DM were 0.799 and 0.852, respectively. The risks of HTN and DM increased by 1.007 and 1.011 times, respectively, for each 1-percentile increase in BMI.The results showed that BMI was associated with the incidence of HTN and DM according to the SRD. The relative distribution of BMI can be used to motivate self-care through providing more detailed information to individuals.

Invasive candidiasis has high mortality rates in immunocompromised patients, causing serious health problems. In mouse models, innate immunity protects the host by rapidly mobilizing a variety of resistance and tolerance mechanisms to systemic

Protein-Protein Interactions (PPIs) play essential roles in diverse biological processes and their misregulations are associated with a wide range of diseases. Especially, the growing attention to PPIs as a new class of therapeutic target is increasing the need for an efficient method of cell-based PPI analysis. Thus, we newly developed a robust PPI assay (SeePPI) based on the co-translocation of interacting proteins to the discrete subcellular compartment 'processing body' (p-body) inside living cells, enabling a facile analysis of PPI by the enriched fluorescent signal. The feasibility and strength of SeePPI (Signal enhancement exclusively on P-body for Protein-protein Interaction) assay was firmly demonstrated with FKBP12/FRB interaction induced by rapamycin within seconds in real-time analysis of living cells, indicating its recapitulation of physiological PPI dynamics. In addition, we applied p53/MDM2 interaction and its dissociation by Nutlin-3 to SeePPI assay and further confirmed that SeePPI was quantitative and well reflected the endogenous PPI. Our SeePPI assay will provide another useful tool to achieve an efficient analysis of PPIs and their modulators in cells. [BMB Reports 2018; 51(10): 527-532].

Lytic induction of latent Epstein-Barr virus (EBV) has been considered as a therapeutic approach for efficient treatment of EBV-associated malignancies. Here, we established a robust assay system quantitatively measuring EBV lytic induction and identified three Euphorbia extracts as strong inducers from a screen of Korean medicinal plant extracts library. Expression of lytic genes were efficiently induced by each Euphorbia extract in SNU-719 (EBV-positive gastric carcinoma cells). Euphorbia pekinensis, out of three extracts, exhibited the most potent lytic-inducing activity. Importantly, treatment with E. pekinensis extract led to an obvious cytotoxic effect on SNU-719 cells, but little on MKN-74 cells (EBV-negative gastric carcinoma cells), indicating the selective oncolytic effect on EBV-positive gastric carcinoma. We further revealed that lytic-inducing activity of E. pekinensis was mediated by PKC/MEK signal. Moreover, we defined two structural analogs of PMA with strong lytic-inducing activity, suggesting their therapeutic applicability for the treatment of EBV-associated gastric carcinoma.

Background Spinal muscular atrophy (SMA) is a rare neuromuscular disease and a leading genetic cause of infant mortality. SMA is caused primarily by the deletion of the survival motor neuron 1 (SMN1) gene, which leaves the duplicate gene SMN2 as the sole source of SMN protein. The splicing defect (exon 7 skipping) of SMN2 leads to an insufficient amount of SMN protein. Therefore, correcting this SMN2 splicing defect is considered to be a promising approach for the treatment of SMA. Purpose This study aimed to identify active compounds and extracts from plant resources to rescue SMA phenotypes through the correction of SMN2 splicing. Study design Of available plant resources, candidates with SMA-related traditional medicine information were selected for screening using a robust luciferase-based SMN2 splicing reporter. Primary hits were further evaluated for their ability to correct the splicing defect and resultant increase of SMN activity in SMA patient-derived fibroblasts. Confirmed hits were finally tested to determine the beneficial effects on the severe Δ7 SMA mouse. Methods SMN2 splicing was analyzed using a luciferase-based SMN2 splicing reporter and subsequent RT-PCR of SMN2 mRNAs. SMA phenotypes were evaluated by the survival, body weights, and righting reflex of Δ7 SMA mice. Results In a screen of 492 selected plant extracts, we found that Brucea javanica extract and its major constituent Bruceine D have SMN2 splicing-correcting activity. Their ability to correct the splicing defect and the resulting increased SMN activity were further confirmed in SMA fibroblasts. Importantly, both B. javanica and Bruceine D noticeably improved the phenotypic defects, especially muscle function, in SMA mice. Reduced expression of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) contributed to the correction of splicing by B. javanica. Conclusion Our work revealed that B. javanica and Bruceine D correct the SMN2 splicing defect and improve the symptoms of SMA in mice. These resources will provide another possibility for development of a plant-derived SMA drug candidate.

The extent to which convergent adaptation to similar ecological niches occurs by a predictable genetic basis remains a fundamental question in biology. Threespine stickleback fish have undergone an adaptive radiation in which ancestral oceanic populations repeatedly colonized and adapted to freshwater habitats. In multiple lakes in British Columbia, two different freshwater ecotypes have evolved: a deep-bodied benthic form adapted to forage near the lake substrate, and a narrow-bodied limnetic form adapted to forage in open water. Here, we use genome-wide linkage mapping in marine × benthic F2 genetic crosses to test the extent of shared genomic regions underlying benthic adaptation in three benthic populations. We identify at least 100 Quantitative Trait Loci (QTL) harboring genes influencing skeletal morphology. The majority of QTL (57%) are unique to one cross. However, four genomic regions affecting eight craniofacial and armor phenotypes are found in all three benthic populations. We find that QTL are clustered in the genome and overlapping QTL regions are enriched for genomic signatures of natural selection. These findings suggest that benthic adaptation has occurred via both parallel and nonparallel genetic changes.

The objectives of this study were to investigate the physicochemical dissolution of chrysotile asbestos and to synthesize nano-sized materials and carbonate minerals from the asbestos via acid dissolution and pH changes. Chrysotile asbestos powder was dissolved in 3 different acids, HCl, HThe objectives of this study were to investigate the physicochemical dissolution of chrysotile asbestos and to synthesize nano-sized materials and carbonate minerals from the asbestos via acid dissolution and pH changes. Chrysotile asbestos powder was dissolved in 3 different acids, HCl, H₂SO₄, and HNO₃, and the solutions were then titrated using NH₄OH and reacted with CO₂. The residual material and precipitates were examined with XRD and TEM-EDS. ICP-AES analysis was also used to investigate the chemical makeup of the solution. The concentration of Mg in the solution was about 1,280 mg/L. The chrysotile became noncrystalline silica after acid treatment (pH = 0). At pH 8.6 and 9.5, the precipitates were amorphous iron oxide and nesquehonite [Mg(HCO3)(OH)·2(H₂O)] after reaction with CO₂. The particle size of the precipitates ranged from 2 to 500 nm. These results indicate that dissolution of chrysotile asbestos using HCl, H₂SO4, and HNO3 can chemically alter chrysotile fibers. Also, the dissolved materials can be used as precursors for other materials such as silica, iron oxide, and carbonates. This process may be useful for the synthesis of silica and iron oxides and for mineral carbonation for carbon sequestration. SO4, and HNO₃, and the solutions were then titrated using NH4OH and reacted with CO₂. The residual material and precipitates were examined with XRD and TEM-EDS. ICP-AES analysis was also used to investigate the chemical makeup of the solution. The concentration of Mg in the solution was about 1,280 mg/L. The chrysotile became noncrystalline silica after acid treatment (pH = 0). At pH 8.6 and 9.5, the precipitates were amorphous iron oxide and nesquehonite [Mg(HCO₃)(OH)·2(H₂O)] after reaction with CO₂. The particle size of the precipitates ranged from 2 to 500 nm. These results indicate that dissolution of chrysotile asbestos using HCl, H₂SO₄, and HNO3 can chemically alter chrysotile fibers. Also, the dissolved materials can be used as precursors for other materials such as silica, iron oxide, and carbonates. This process may be useful for the synthesis of silica and iron oxides and for mineral carbonation for carbon sequestration.

At present, we suffer from various environmental issues such as air pollution and rapid weather change. Air pollution is usually caused by the use of fossil fuels. To overcome the environmental issues, LIBs are reasonable candidates. In these days, lithium ion batteries (LIB) are very promising power suppliers for electronic devices, electrical vehicles (EV), and energy storage system (ESS) because of their high power densities.[1] Although the LIB has advantages compared to other power sources, LIBs with a liquid electrolyte have safety issues such as explosion and fire contributed by thermal or chemical instability. All-solid-state batteries are the solution to the problem of LIBs with liquid electrolytes. All-solid-state batteries have many advantages such as high energy densities, high stability, and applying high voltages compared to conventional LIBs.[2] As the portable and miniaturization of electronic devices and the development of wearable devices are to be in the spotlight, the development of a power supply for drive them is indispensable. The type of batteries that can meet this demand is an all-solid-state thin-film battery. Thickness of thin-film batteries is about 10 μm, which makes it suitable for power source of miniaturized electronic devices such as smart cards, RFID tags and medical devices. All-solid-state thin-film batteries also have better thermal stability than conventional Li-ion batteries. Higher capacity of thin-film batteries can be realized by applying high voltages. The key to the performance of all-solid-state thin-film batteries is a solid electrolyte. In order to deposit thin-film electrolytes, there are various available techniques such as a sputter, plasma laser deposition (PLD), e-beam evaporator, and so on. Among these techniques, the sputtering technique has an advantage compared to other deposition techniques. The sputtering techniques could deposit oxide and nitride materials. In addition, sputtering techniques are simple process and can be deposition with thin films uniformly. Comparing PLD and molecular beam epitaxy (MBE), the sputtering techniques are lower cost and low temperature for deposition. Therefore, sputters are suitable for commercialization. Generally, solid electrolytes are classified under oxide system and sulfide system. While sulfide electrolytes have high ionic conductivity and instability, oxide electrolytes have low ionic conductivity and high stability. A lot of oxide based solid state electrolytes were researched. The oxide-based solid electrolytes include LiPON, Li7La3Zr2O12 (LLZO), Li1+xAlxTi2-x(PO4)3(LATP), and lithium boron oxynitride. Among them, LiPON thin-film electrolytes are representative and commonly used as a thin-film electrolyte. However, since the ionic conductivity of LiPON is relatively low, it is necessary to improve the low ionic conductivity. In this study, a new lithium silicon oxynitride (LiSiON) thin-film electrolyte was deposited by RF sputtering technique. Surface morphologies and cross-sectional views of the thin-film electrolyte were characterized by field emission scanning electron microscope (FESEM). The thin film showed smooth surface without any cracks and pinholes. It can be thought that the smooth surface could decrease interfacial resistance between electrolyte and electrodes. In addition, surface morphologies were also characterized by atomic force microscopy (AFM). The sputtering rates were calculated by thickness of thin films on cross sectional views. Structural properties of the thin films were characterized by x-ray diffraction (XRD). The thin film showed amorphous properties compared to the target material which is a crystalline material. In addition, structural properties of the thin film were also characterized by transmission electron microscope (TEM). The thin film showed also amorphous properties with partially crystalline in LiSiON structures deposited by RF sputtering. Ionic conductivity of LiSiON was measured by electrochemical impedance spectroscopy (EIS). Cu thin films used as blocking electrodes with 150nm thickness were deposited by a direct current (DC) magnetron sputtering using a target with 2-inch diameter. The DC power and working pressure were set on 30W and 7 mTorr in Ar atmosphere, respectively. LiSiON thin film was deposited by an RF magnetron sputter at 200W power using Li4SiO4 target with 4-inch diameter in Ar/N2 (2:8) atmosphere. Ionic conductivity of the LiSiON thin film showed 2.47 ´ 10-6 (S/cm) which is similar to other lithium oxide thin films. For this reason, LiSiON thin-film electrolytes are research-worthy materials for use in all-solid-state thin-film batteries. Reference [1] M. Armand, J. Tarascon, Nature, 451, 652 (2008). [2] Q. Wang, P. Ping, X. Zhao, G. Chu, J. Sun, et al., J. Power Sources, 208, 210 (2012).

The necessity of developing new types of energy conversion and storage systems is evident by the rapidly decreasing fossil fuels and the continuously growing environmental issues. Coupling of lithium ion secondary batteries and photovoltaic cells is a reasonable candidate of new types of energy transform and storage system to reduce environmental concerns. Solar cells can ensure sustainable access to electrical power for charging LIBs anywhere around the world with no air pollution, hazardous waste or noise. Accordingly, the solar cell technology that generates electricity from the sunlight [1], could offer a viable approach to ‘self-charging’ of LIBs. However, most current solar cells, especially polymer solar cells, generally show low current densities and power conversion efficiencies, and to improve this we used perovskite solar cell for power supply of self-chargeable batteries. The recent availability of high-performance perovskite solar cells (PSCs) could not only facilitate the development of highly efficient (up to ~ 20 %) [2] and low cost solar cells for practical applications but also allow for the integration of PSCs into various energy systems. One of the important problems of PSC-LIB coupling is that when charging, the voltage of the PSCs must be higher than the operating voltage of the LIBs. If the above conditions are not established, PSCs may cause discharge of the LIBs. The most structurally stable LiFePO4(LFP)-LTO(Li4Ti5O12) batteries were used for coupling. In the case of LFP-LTO batteries, the OCV(open circuit voltage) value has a low voltage of 1.85V. It was confirmed that stable self-charging is achieved by connecting it to a manufactured PSCs pack with a charging voltage of 2.1 V. This work clearly indicates that the PSC-LIB units developed in this study hold great promise for potential applications as self-chargeable batteries to various portable electronics. In this study, we have fabricated lithium-ion pouch cell and coin cell based on LFP and (LTO) as a cathode and an anode, respectively. The cathode was fabricated by blending LFP powder with carbon black (Super P) and polyvinylidene difluoride (PVDF) at a weight ratio of 8:1:1. The anode was also prepared in the same way as the cathode using LTO powder and N-Methyl-2-pyrrolidone (NMP) was used as the solvent, respectively. The Electrolyte was used 1.2 M LiPF6 in a 1:1(v/v, %) mixture of ethylene carbonate and dimethyl carbonate. Pouch cell was fabricated with size of 3 cm x 5 cm. Ni and Al were used as cathode and anode lead tabs, respectively. The LIBs were assembled as the CR 2032 coin-type cells and pouch cells in an Ar-filled glove box. Structural properties and chemical compositions of LFP and LTO powders were investigated by x-ray diffraction (XRD) and x-ray photoelectron spectroscopy (XPS). The XRD pattern shows that the LiFePO4 cathode sheets are crystalline. The powder and surface morphologies of electrode sheet were characterized by FE-SEM. The primary particles size was identified as approximately 50 to 150 nm and the secondary particles size approximately 10mm. The electrochemical performance of LFP and LTO half cells and the LFP-LTO full cell were conducted by cyclic voltammetry and charge/discharge cycle tests at various current densities in the voltage ranges. Electrochemical impedance spectroscopy (EIS) was performed in frequency range from 0.1 Hz to 1 MHz, using 10 mV ac signals at room temperatures. LFP-LTO pouch cells showed good cycling stability a wide range of C-rates from 0.1 to 1.0 C with charge/discharge capacities of 142/138 mAhg-1 at 0.1 C and 152/144 mAhg-1 at 1.0 C. As a result, LiB-PSC coupling enabled the implementation of self-chargeable batteries. Finally, Perovskite solar cells and the Li-ion battery coupling were tested for a self-chargeable device. References Green, M. A. Solar cells: Operating Principles, Technology, and System Applications (Prentice-Hall, 1982). Lee, M. M., Teuscher, J ., Miyasaka, T., Murakami, T. N. & Snaith, H. J. Efficient hybrid solar cells based on meso-superstructured organometal halide perovskites. Science 338, 643-647 (2012)

Spinal muscular atrophy (SMA) is caused by the mutation or deletion of the survival motor neuron 1 (SMN1) gene. Only ∼10% of the products of SMN2, a paralogue of SMN1, are functional full-length SMN (SMN-FL) proteins, whereas SMN2 primarily produces alternatively spliced transcripts lacking exon 7. Reduced SMN protein levels in SMA patients lead to progressive degeneration of spinal motor neurons (MNs). In this study, we report an advanced platform based on an SMN2 splicing-targeting approach for SMA drug screening and validation using an SMN2 splicing reporter cell line and an in vitro human SMA model through induced pluripotent stem cell (iPSC) technology. Through drug screening using a robust cell-based luciferase assay to quantitatively measure SMN2 splicing, the small-molecule candidate compound rigosertib was identified as an SMN2 splicing modulator that led to enhanced SMN protein expression. The therapeutic potential of the candidate compound was validated in MN progenitors differentiated from SMA patient-derived iPSCs (SMA iPSC-pMNs) as an in vitro human SMA model, which recapitulated the biochemical and molecular phenotypes of SMA, including lower levels of SMN-FL transcripts and protein, enhanced cell death, and reduced neurite length. The candidate compound exerted strong splicing correction activity for SMN2 and potently alleviated the disease-related phenotypes of SMA iPSC-pMNs by modulating various cellular and molecular abnormalities. Our combined screening platform representing a pMN model of human SMA provides an efficient and reliable drug screening system and is a promising resource for drug evaluation and the exploration of drug modes of action.

The objectives of this study were to recover silica and iron oxides and sequestration using serpentine via various acid dissolution and pH swing processes. Serpentine collected from Guhang-myeon in S. Korea were mainly composed of antigorite and magnetite consisting of (45.3 wt.%), MgO (41.3 wt.%), (12.2 wt.%). Serpentine pulverized () and then dissolved in 3 different acids, HCl, , . Residues treated with acidic solution were recovered from the solution (step 1). And then the residual solution containing dissolved serpentine was titrated using . And pH of the solution increased up to pH

In nature, multiple adaptive phenotypes often coevolve and can be controlled by tightly linked genetic loci known as supergenes. Dissecting the genetic basis of these linked phenotypes is a major challenge in evolutionary genetics. Multiple freshwater populations of threespine stickleback fish (Gasterosteus aculeatus) have convergently evolved two constructive craniofacial traits, longer branchial bones and increased pharyngeal tooth number, likely as adaptations to dietary differences between marine and freshwater environments. Prior QTL mapping showed that both traits are partially controlled by overlapping genomic regions on chromosome 21 and that a regulatory change in Bmp6 likely underlies the tooth number QTL. Here, we mapped the branchial bone length QTL to a 155 kb, eight-gene interval tightly linked to, but excluding the coding regions of Bmp6 and containing the candidate gene Tfap2a. Further recombinant mapping revealed this bone length QTL is separable into at least two loci. During embryonic and larval development, Tfap2a was expressed in the branchial bone primordia, where allele specific expression assays revealed the freshwater allele of Tfap2a was expressed at lower levels relative to the marine allele in hybrid fish. Induced loss-of-function mutations in Tfap2a revealed an essential role in stickleback craniofacial development and show that bone length is sensitive to Tfap2a dosage in heterozygotes. Combined, these results suggest that closely linked but genetically separable changes in Bmp6 and Tfap2a contribute to a supergene underlying evolved skeletal gain in multiple freshwater stickleback populations.

In this paper, we propose an improved algorithm for superpixel segmentation using linear spectral clustering with mean shift filtering. The proposed method adopts mean shift as pre-processing for superpixel segmentation. The proposed method uses this pre-processed image for spectral clustering, which produces more concise and uniform superpixels. Experimental results show that it gives superpixels with relatively compact and uniform segments. The proposed method reduces irregular and scratchy boundaries of segments compared with the existing superpixel segmentation methods.

Objective: It is well known that Schwann cells play an important role in Wallerian degeneration after peripheral nerve injury. Previously, we reported that toll-like receptor 3 (TLR3) is expressed on Schwann cells, implicating its role in Schwann cell activation during Wallerian degeneration. In this study, we tested this possibility using TLR3 knock-out mice. Methods: Sciatic nerve-crush injury was induced in wild-type and TLR3 knock-out mice. Histological sections of the sciatic nerve were analyzed for Wallerian degeneration on days 3 and 7 after injury. The level of macrophage infiltration was measured by real-time RT-PCR, flow cytometry and immunohistochemistry. The macrophage-recruiting chemokine gene expressions in the injured nerve were determined by real-time RT-PCR. Results: In TLR3 knock-out mice, the nerve injury-induced axonal degeneration and subsequent axonal debris clearance were reduced compared to in wild-type mice. In addition, nerve injury-induced macrophage infiltration into injury sites was attenuated in TLR3 knock-out mice and was accompanied by reduced expression of macrophage-recruiting chemokines such as CC-chemokine ligands (CCL)2/MCP-1, CCL4/MIP-1β and CCL5/RANTES. These macrophage-recruiting chemokines were induced in primary Schwann cells upon TLR3 stimulation. Finally, intraneural injection of polyinosinic-polycytidylic acid, a synthetic TLR3 agonist, induced macrophage infiltration into the sciatic nerve in vivo. Conclusion: These data show that TLR3 signaling contributes to Wallerian degeneration after peripheral nerve injury by affecting Schwann cell activation and macrophage recruitment to injured nerves.

Significance Ribonucleotide reductases (RNRs) catalyze nucleotide reduction via complex radical chemistry, providing deoxynucleotides for DNA synthesis in all domains of life. Many anaerobic bacteria and archaea contain the class III O 2 -sensitive RNR, and those that have been studied to date couple nucleotide reduction to formate oxidation. Here we report the characterization of a second class III RNR subtype that couples nucleotide reduction to the oxidation of thioredoxin. Because of the central role of formate and thiols in many anaerobic processes, the distribution of class III RNRs among different organisms may shed light on aspects of anaerobic biochemistry.

Differences in biomolecular sequence and function underlie dramatic ranges of appearance and behavior among species. We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. Metazoans have a higher proportion of heteromeric bZIP interactions and more network complexity than the single-cell species. The metazoan bZIP interactomes have broadly similar structures, but there has been extensive rewiring of connections compared to the last common ancestor, and each species network is highly distinct. Many metazoan bZIP orthologs and paralogs have strikingly different interaction specificities, and some differences arise from minor sequence changes. Our data show that a shifting landscape of biochemical functions related to signaling and gene expression contributes to species diversity.