Search

The relationships among species in the genus Eranthis Salisb. were investigated using single nucleotide polymorphisms (SNPs) of the nuclear DNA internal transcribed spacer 1, 2 region (nrITS) and the chloroplast trnL-trnF interspacer region (cpIS). Phylogenetic relationships based on the nrITS and cpIS were inferred with posterior probabilities with STRUCTURE analysis and the neighbor-joining method. Two major clades from nrITS and cpIS were consistent with species with yellow sepals in E. hyemalis, E. cilicica, E. longistipitata and the hybrid E. ×tubergenii; and white sepals in E. sibirica, E. longituba, E. albiflora, E. stellata, E. pungdoensis, E. byunsanensis, and E. pinnatifida. The phylogenetic tree of nrITS formed more subclades than the tree of cpIS, which suggested that nrITS SNPs are useful molecular markers for phylogenetic studies in the genus Eranthis. Only the SNPs of cpIS in E. pungdoensis accessions had a deletion at positions 259–420, and the posterior probability values (PPVs) assigned E. pungdoensis to population 4, which suggested that E. pungdoensis is different from E. byunsanensis. Therefore, E. byunsanensis and E. pungdoensis are considered to be true-to-type based on q-values because the PPVs were greater than 0.9 in both species based on the STRUCTURE analysis of nrITS SNPs. Significant genetic variation in E. stellata collected in Goesan-kun and Mt. Mugap, Korea indicated a potential gene flow among closely related E. byunsanensis, E. pinnatifida, E. sibirica, and E. stellata that could be due to geographic proximity in their distributions. E. stellata from Mt. Mugap showed mixed PPVs for E. stellata and E. byunsanensis, therefore, E. byunsanensis might be a possible hybrid origin for E. stellata collected from Goesan-kun and Mt. Mugap.

We designed a bacterio-mimetic nanoparticle that can noncovalently control the orientation of attached antibodies. Liposomes with Fc-binding peptide (FcBP), formulated using FcBP-conjugated PEGylated lipid, were used as model nanoparticles. Compared with control nanoparticles surface-modified with antibody covalently attached via maleimide functional groups (Mal-NPs), FcBP-capped nanoparticles (FcBP-NPs) exhibited greater binding affinity to the target protein. Human epidermal growth factor receptor 2 (HER2)-specific antibody-modified FcBP-NPs (HER2/FcBP-NPs) showed 5.3-fold higher binding affinity to HER2 than isotype IgG antibody-modified NPs, and 2.6-fold higher affinity compared with anti-HER2 antibody-conjugated Mal-NPs. Cellular uptake of HER2/FcBP-NPs in HER2-positive cells was significantly higher than that of other formulations. The biodistribution of HER2/FcBP-NPs was higher than that of antibody-conjugated NPs in HER2-positive tumor tissues, but not in HER2-negative tumors. Our findings suggest the potential of bacteriomimetic nanoparticles for controlling the orientation of antibody attachment. These nanoparticles may have diverse applications in nanomedicine, including drug delivery, molecular imaging, and diagnosis.

CCW702 is a bispecific antibody that combines the specificity of an imaging ligand with the potency of a T cell immunotherapy., Despite the development of next-generation antiandrogens, metastatic castration-resistant prostate cancer (mCRPC) remains incurable. Here, we describe a unique semisynthetic bispecific antibody that uses site-specific unnatural amino acid conjugation to combine the potency of a T cell–recruiting anti-CD3 antibody with the specificity of an imaging ligand (DUPA) for prostate-specific membrane antigen. This format enabled optimization of structure and function to produce a candidate (CCW702) with specific, potent in vitro cytotoxicity and improved stability compared with a bispecific single-chain variable fragment format. In vivo, CCW702 eliminated C4-2 xenografts with as few as three weekly subcutaneous doses and prevented growth of PCSD1 patient-derived xenograft tumors in mice. In cynomolgus monkeys, CCW702 was well tolerated up to 34.1 mg/kg per dose, with near-complete subcutaneous bioavailability and a PK profile supporting testing of a weekly dosing regimen in patients. CCW702 is being evaluated in a first in-human clinical trial for men with mCRPC who had progressed on prior therapies (NCT04077021).

Vitamin D status is inversely associated with the prevalence of metabolic syndrome (MetS). Whether this is true in the elderly without vitamin D deficiency is rarely investigated. Our data source is a cross-sectional survey of 1,966 community-dwelling elderly Taiwanese in 2012. An overnight fasting blood were obtained for biochemistry variables. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D3 [25(OH)D] concentration

Background Various cytokines have been studied to determine their functions in the pathogenesis of allergic diseases and their potential as therapeutic targets, but the roles and clinical applicability of many of these cytokines still remain unclear. Objective We aimed to measure the plasma levels of eight cytokines known to be relevant to allergic diseases, and to determine their association with the diagnostic characteristics of allergic patients. Methods The levels of a panel of eight cytokines (IL-5, IL-10, IL12p70, Leptin, CXCL5/ENA-78, CCL2/MCP-1, PDGFBB, and VEGF) were measured in plasma obtained from 83 allergic patients. We investigated whether the cytokine levels differed between children and adults. Statistical analyses were then performed to examine their association with the diagnostic characteristics of allergic patients. Results The levels of leptin, CCL2/MCP-1, PDGFBB, and VEGF were significantly higher in adult patients with allergic rhinitis than in children. Among patients with asthma, the levels of leptin and PDGFBB were elevated in adults. PDGFBB and VEGF levels were significantly associated with asthma. Interestingly, there was a significant association between VEGF level and recurrent wheezing regardless of the analyzed conditions. The levels of VEGF and PDGFBB or CCL2/MCP-1 showed a significant increase together in the presence of recurrent wheezing in child patients. CONCLUSIONonclusion: The plasma levels of four cytokines, particularly VEGF, showed significant associations with some diagnostic characteristics in allergic patients. We suggested that plasma VEGF, which performs pleiotropic functions in allergic responses, could serve as a serological marker relevant to recurrent wheezing in allergic patients.

The specialized membrane proteins’ function, puzzling in a single bacterial cell, becomes apparent when the cell joins a large colony.

Gelation maintains aberration-preventing protein-density gradients in the cephalopods’ eyes.Gelation maintains aberration-preventing protein-density gradients in the cephalopods’ eyes.

Significance Chimeric antigen receptor (CAR) T cell therapy represents a powerful strategy in immuno-oncology. Nevertheless, associated life-threatening toxicities and chronic B cell aplasia have underscored the need to control engineered T cells in the patient. To address these challenges, we have previously developed a switchable CAR (sCAR) T cell platform that allows dose-titratable control over CAR T cell activity by using antibody-based switches. Here, we demonstrate in a syngeneic murine model that the switchable platform can impart antitumor efficacy while dissociating long-term persistence from chronic B cell aplasia. Further, the functional reversibility of the switchable platform can be leveraged to incorporate “rest” phases through cyclical dosing of the switch to enable the induction of a robust central memory population for in vivo, on-demand expansion of sCAR T cells., Chimeric antigen receptor (CAR) T cells with a long-lived memory phenotype are correlated with durable, complete remissions in patients with leukemia. However, not all CAR T cell products form robust memory populations, and those that do can induce chronic B cell aplasia in patients. To address these challenges, we previously developed a switchable CAR (sCAR) T cell system that allows fully tunable, on/off control over engineered cellular activity. To further evaluate the platform, we generated and assessed different murine sCAR constructs to determine the factors that afford efficacy, persistence, and expansion of sCAR T cells in a competent immune system. We find that sCAR T cells undergo significant in vivo expansion, which is correlated with potent antitumor efficacy. Most importantly, we show that the switch dosing regimen not only allows control over B cell populations through iterative depletion and repopulation, but that the “rest” period between dosing cycles is the key for induction of memory and expansion of sCAR T cells. These findings introduce rest as a paradigm in enhancing memory and improving the efficacy and persistence of engineered T cell products.

International audience; The simian immunodeficiency virus (SIV)/macaque model of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome pathogenesis is critical for furthering our understanding of the role of antibody responses in the prevention of HIV infection, and will only increase in importance as macaque immunoglobulin (IG) gene databases are expanded. We have previously reported the construction of a phage display library from a SIV-infected rhesus macaque (Macaca mulatta) using oligonucleotide primers based on human IG gene sequences. Our previous screening relied on Sanger sequencing, which was inefficient and generated only a few dozen sequences. Here, we re-analyzed this library using single molecule, real-time (SMRT) sequencing on the Pacific Biosciences (PacBio) platform to generate thousands of highly accurate circular consensus sequencing (CCS) reads corresponding to full length single chain fragment variable. CCS data were then analyzed through the international ImMunoGeneTics information system®(IMGT®)/HighV-QUEST (www.imgt.org) to identify variable genes and perform statistical analyses. Overall the library was very diverse, with 2,569 different IMGT clonotypes called for the 5,238 IGHV sequences assigned to an IMGT clonotype. Within the library, SIV-specific antibodies represented a relatively limited number of clones, with only 135 different IMGT clonotypes called from 4,594 IGHV-assigned sequences. Our data did confirm that the IGHV4 and IGHV3 gene usage was the most abundant within the rhesus antibodies screened, and that these genes were even more enriched among SIV gp140-specific antibodies. Although a broad range of VH CDR3 amino acid (AA) lengths was observed in the unpanned library, the vast majority of SIV gp140-specific antibodies demonstrated a more uniform VH CDR3 length (20 AA). This uniformity was far less apparent when VH CDR3 were classified according to their clonotype (range: 9-25 AA), which we believe is more relevant for specific antibody identification. Only 174 IGKV and 588 IGLV clonotypes were identified within the VL sequences associated with SIV gp140-specific VH. Together, these data strongly suggest that the combination of SMRT sequencing with the IMGT/HighV-QUEST querying tool will facilitate and expedite our understanding of polyclonal antibody responses during SIV infection and may serve to rapidly expand the known scope of macaque V genes utilized during these responses.

The cardiovascular and liver protection of carnitine (CNT) in a high-fat diet was investigated. Male C57BL/6 mice were divided randomly into four groups: 1) CON: Control, 2) HFD: high-fat diet, 3) CNTL: HFD + 500 mg CNT/kg BW, and 4) CNTH: HFD + 1500 mg CNT/kg BW. After a 25-week experimental period, CNT supplementation reduced (p

고유식물인 꼬리말발도리는 팔공산, 달음산, 가지산과 운문산 등 경상남북도에 제한적으로 분포한다. 본 연구대상인 4개 집단의 크기는 달음산의 최소 100개체에서 운문산 집단이 최대 3,500개체까지이다. 인공수분실험 결과,생식양식은 완전 타가수분이며, 주요 관찰 화분매개자는 Lasioglossum exiliceps (Vachal)과 호리꽃등에 [Allograptabalteata (de Geer)]였다. 동위효소로 유전적 다양성을 측정한 결과, 종 수준에서의 평균적인 유전다양성은 유전자좌당 평균 대립유전자수(A

Plants that have been treated as Sorbus commixta on Ulleung Island, Korea, show morphological variability and their taxonomy is unclear. We extensively studied the morphology of wild populations of these plants and found that they can be distinguished from S. commixta by their larger fruits and flowers and wider inflorescences. Here we describe and illustrate them and propose them as representing a new species, S. ulleungensis. An updated key to the five Korean species of Sorbus including the new species is provided.

Cerebral serotonin metabolism has an important but controversial role in obesity. However, it is not given enough attention in morbidly obese young adults. We used single photon emission computed tomography (SPECT) with [I-123]-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) to investigate changes in serotonin transporter (SERT) availability in 10 morbidly obese young adults without an eating disorder (M/F = 5/5, body mass index (BMI): 40.3 ± 4.1 kg/m2, percentage of body fat (BF%): 46.0 ± 3.9%) and 10 age- and sex-matched non-obese controls (BMI: 20.3 ± 1.2 kg/m2, BF%: 20.6 ± 8.9%). All participants underwent SPECT at 10 min and 6 h after an injection of 200 MBq of [I-123]-ADAM. The SERT binding site (midbrain) was drawn with cerebellum normalization. The BF% and fat distribution were measured using dual-energy X-ray absorptiometry. The midbrain/cerebellum SERT binding ratios (2.49 ± 0.46 vs. 2.47 ± 0.47; p = 0.912) at 6 h were not significantly different between groups, nor was the distribution of the summed images at 10 min (1.36 ± 0.14 vs. 1.35 ± 0.11; p = 0.853). There were no significant correlations between midbrain/cerebellum SERT binding ratio and age, BMI, BF%, or fat distribution. No significant difference in SERT availability in the midbrain between morbidly obese and non-obese young adults without an eating disorder indicates an unmet need for investigating the role of cerebral serotonin in obesity.

In this study, steam reforming reaction and surface characteristics of Ni metal foam plate were investigated. Valence state of Ni could be changed by pretreatment, and metallic Ni species exposed on surface as a active site play important role in steam reforming reaction. Porous catalytic membrane also was prepared by mixing of Ni metal foam plate and Ni-YSZ catalyst to control the pore size and assign the catalytic function in Ni metal foam plate. In SEM analysis results, Pore size of Ni metal foam plate could be controlled and Ni-YSZ catalyst well dispersed on surface. Ni based porous catalytic membrane had a similar steam reforming activity regardless of space velocity.

The original version of this article unfortunately contained a mistake. The name of Chin-Sung Chang was presented incorrectly. The corrected author list is given above.

Subalpine species, Sorbus pohuashanensis in the Korean peninsula, which is assumed to be evolved from hybridization between S. commixta and an unknown species based on the flavonoids data. Morphometric analysis was conducted on the basis of 19 leaf and flower (or fruit) characters. A total of 721 samples in 13 pop- ulations of Sorbus pohuashanensis and S. commixta from Korea and additional specimens of S. commixta, S. pohuashanensis, and S. wilsoniana from Japan and China were examined to reveal the hybridization patterns and morphological differences. We found a preliminary evidence where Korean mountain rowan is more related to a Chinese inland taxon, S. wilsoniana, rather than Northeastern Chinese S. pohuashanensis in terms of fla- vonoids. The current morphological structure of the Korean mountaion rowan, however, which is more similar to S. commixta, was neither associated with that of S. wilsoniana nor that of S. pohuashanensis. This indicates that this morphological variation represents an intermediate of S. commixta and S. wilsoniana via a more ancient hybridization event in terms of qualitative characters, such as stipules, buds, and carpels. These morphometric differences together with other distinguishing characteristics suggest that the Korean mountain rowan should be considered as a conspecific species of S. commixta, although this demonstration of hybridization with the cur- rent phenetic species concept contradicts longstanding historical species concept.

Light with two faces, beneficial and harmful effects is an important signal for every living cell. Optimal adaptation to light environment enhances the fitness of an organism and survival in nature. Understandings of light quality and plant growth provide with the economical guides for artificial light sources like LEDs. Compared with those under white light, the 1 week seedlings of Chinese cabbage (Brassica rapa) under monochromic red and blue light showed normal development and growth. In contrast to extremely long and etiolated hypocotyls of the seedlings under dark, those under far-red etiolated were extremely short. Based on the microarray analysis, blue light induced the vigorous development and growth and two fold changes of transcripts than red light condition. To have insight of gene products under different light qualities conditions, GO term enrichments were calculated and each gene according to their GO terms were categorized. The blue and red lights affected the expressions of genes related to biological process. Especially, the genes related to metabolic process and developmental process and plastid and chloroplast in the cellular component category were induced under blue light. This study provided the molecular biological evidence for various light qualities on the growing process of B. rapa.

The genetic or functional inactivation of the p53 pathway plays an important role with regards to disease progression from the chronic phase (CP) to blast phase (BP) and imatinib treatment response in chronic myeloid leukemia (CML). Two functional single nucleotide polymorphisms (SNPs), p53 R72P and MDM2 SNP309, are associated with alternation of p53 activity, however the association regarding CML susceptibility and BP transformation under imatinib treatment is unclear. The MDM2 SNP309 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism and confirmed by direct sequencing from 116 CML patients, including 104 in the CP at diagnosis, and 162 healthy Taiwanese controls. The p53 R72P polymorphism was examined in all CML patients. The SNP309 G/G genotype was associated with an increased risk of CML susceptibility (OR: 1.82, 95% CI: 1.03-3.22, P = 0.037), and an earlier age of disease onset (log-rank P = 0.005) compared with the T/T + T/G genotypes. Higher MDM2 mRNA expression was found in G/G genotype compared with T/T (P = 0.034) and T/T + T/G (P = 0.056) genotypes. No associations were found between the p53 R72P genotypes and clinical parameters and survival outcomes. Among 62 CP patients receiving imatinib as first-line therapy, the G/G genotype was associated with a shorter blast-free survival (log-rank P = 0.048) and more clonal evolution compared with the T/T + T/G genotypes. In patients with advanced diseases at diagnosis, the G/G genotype was associated with a poor overall survival (log-rank P = 0.006). Closely monitoring CML patients harboring the G/G genotype and further large-scale studies are warranted.

The conservation status of an endemic perennial herb, Hanabusaya asiatica (Nakai) Nakai (Cam-panulaceae) was determined by applying the IUCN risk assessment criteria from our field study and availablespecimen data. Also, the GIS technology was used to develop a species distribution map to calculate the extentof occurrence (EOO) and area of occupancy (AOO) for the taxon. After two years of continuous field studies,269 mature individuals were found in four localities in 2011, while 216 mature individuals were confirmed inthree localities in 2012. Based on the following data, such as EOO (2,742 km 2 ), AOO (76 km 2 ) and estimatedpopulation size of mature individuals, the taxon, which is known as 20 localities in Korean peninsula, is eval-uated as the category of Endangered (EN). A major difficulty in application of IUCN criteria to Korean rareplants were the lack of essential biological information and understanding the correct knowledge of the IUCNcriteria in previous Korean studies. Sound conclusions regarding the conservation status of individual speciesrequire more intensive population studies, observations, and applying IUCN assessment procedures correctly.

Diagnosis of and therapy for early-stage tumors has the potential to decrease morbidity and mortality among patients with such malignancies. Although promising advances in imaging technology and other diagnostic modalities have been achieved, evidence that primary cancers begin shedding neoplastic cells into the circulation at an early stage is accumulating. Specifically, approximately 10 6 cells are shed daily per gram of tumor. Thus, circulating tumor cells (CTCs) are a potential source for the noninvasive and early diagnosis of cancers. Several studies have indicated that a preoperative detection of micrometastases may reflect the transient shedding of tumor cells, metastatic potential, or residual disease, but that postoperative micrometastases are likely to indicate minimal residual disease. Such neoplastic cells may be present in the bloodstream in very low numbers and would be difficult to detect by conventional methods. In this article, we introduce a highly sensitive gene chip analysis method, developed from a colorimetric membrane array into a weighted enzymatic chip array, to detect the gene clusters of CTCs. This gene chip method provides a fast and accurate analysis of gene clusters, with performance that is substantially better than that of traditional biochemical examinations. The development of this gene chip solves the problem of costs and artifacts that hampers traditional detection methods, and thus marks an important milestone in the field of clinical diagnosis.

A new process for advanced wastewater treatment process has been devised with auxiliary treatment unit employing the ammonia oxidizing photo-catalytic thin film. In winter time, due to low water temperature, conventional nitrogen removal treatment experiences almost no nitrification by nitrifying bacteria. To solve the problem and to meet the governmental effluent guideline the treated water has been recycled through the auxiliary unit in which the auxiliary system was applied with the thin film coating photo-catalyst. This study also identifies the characteristics of the thin film coating-photo-catalyst through XRD, SEM and analyzes the ammonia nitrogen removal efficiency by using the thin film coating photo-catalyst in the reactor which resembles a sewage treatment process. The evaluation of the entire process of biological treatment in accord with the application of thin film coating photo-catalyst was performed through computer simulation. A relevant computer model for mass balance was made and utilized to select proper optimal operating condition such as recycle ratio. Result shows the proposed new process has potential applicability to renovate existing treatment plants.

PURPOSE The prevalence of allergic diseases is known to be associated with both demographic and environmental factors. Herein, we aimed to determine significant factors associated with the prevalence of allergic diseases and with total immunoglobulin E (tIgE) and specific immunoglobulin E (sIgE) levels in Korea. METHODS We analyzed unweighted data collected by the 2010 Korea National Health and Nutrition Examination Survey for 2,342 subjects who underwent serum tests for tIgE and sIgE to Dermatophagoides farinae, dog, and Blattella germanica, representing a sample of 16,003,645 citizens, by considering the sample weight and stratification. RESULTS The overall prevalence of self-reported allergic diseases was 37.6%. The prevalence rates of allergic rhinitis and atopic dermatitis decreased with age, whereas the asthma prevalence was not affected by the age of the subjects. When analyzed according to the type of allergic diseases, the prevalence of self-reported allergic disease was significantly associated with various factors (e.g. age, occupation, living in urban areas, and depression). The tIgE level decreased with age, but later increased. Elevation of tIgE was significantly associated with male sex, type of occupation, obesity, and smoking status. However, the risk factors for the increased sIgE levels to each allergen were quite different. Sensitization to D. farinae was more likely in young subjects, whereas the prevalence of sensitization to B. germanica was significantly higher in subjects with male sex, residing in a house (houses), and with glucose intolerance. Finally, young age and the smoking status were significantly associated with sensitization to dog. CONCLUSIONS Various demographic and environmental factors were significantly associated with the prevalence of self-reported allergic diseases and the levels of tIgE and sIgE to D. farinae, B. germanica, and dog in Korea.

Retinoid X receptors (RXRs) are highly conserved members of the nuclear hormone receptor family that mediate various physiological processes in vertebrates and invertebrates. We examined the expression patterns of RXR in the ascidian Halocynthia roretzi across a wide range of tissues and stages of embryo development, as well as the regulation of gene transcription by the ascidian RXR. H. roretzi RXR cDNA ( HrRXR ) was cloned from 64-cell stage embryos. The overall amino acid sequence of HrRXR showed high sequence identity with a urochordate Ciona intestinalis RXR (58%), but the ligand-binding domain of HrRXR was more similar to vertebrate orthologs than to those of invertebrate RXRs. Based on a phylogenetic analysis, HrRXR belongs to a group of urochordates that are separate from vertebrate RXRs, showing a clear evolutionary history. Real-time quantitative polymerase chain reaction and whole-mount in situ hybridization analyses revealed that the HrRXR mRNA is of maternal origin during embryogenesis, and in the examined adult tissues it is expressed in the muscles, gills, gonads, and the hepatopancreas. Immunofluorescence and immunohistochemical staining demonstrated that HrRXR is localized to the nucleus and highly expressed in the gills and hepatopancreas. Unlike human RXRα, HrRXR did not show 9- cis retinoic acid- and bexarotene (LGD1069)-dependent transactivation. While a synthetic ligand for farnesoid X receptor (FXR), GW4064, did not increase the transcriptional activation in HrRXR- or HrRXR/HrFXR-transfected HEK-293 cells, the ligand showed weak but significant activity for a single amino acid mutant of HrRXR ( Phe 231 Cys ) and HrFXR cotransfected cells. The present study suggests that the marine invertebrate chordate RXR may possess endogenous ligands that are different than vertebrate RXR ligands and which function during early embryonic stages.

Fatty acid synthase (FASN) is a potential therapeutic target for treatment of cancer and obesity, and is highly elevated in 30% of HER2-overexpressing breast cancers. Considerable interest has developed in searching for novel FASN inhibitors as therapeutic agents in treatment of HER2-overexpressing breast cancers. Amentoflavone was found to be effective in suppressing FASN expression in HER2-positive SKBR3 cells. Pharmacological inhibition of FASN by amentoflavone specifically down-regulated HER2 protein and mRNA, and caused an up-regulation of PEA3, a transcriptional repressor of HER2. In addition, pharmacological blockade of FASN by amentoflavone preferentially decreased cell viability and induced cell death in SKBR3 cells. Palmitate reduced the cytotoxic effect of amentoflavone, as the percentage of viable cells was increased after the addition of exogenous palmitate. Amentoflavone-induced FASN inhibition inhibited the translocation of SREBP-1 in SKBR3 cells. Amentoflavone inhibited phosphorylation of AKT, mTOR, and JNK. The use of pharmacological inhibitors revealed that the modulation of AKT, mTOR, and JNK phosphorylation required synergistic amentoflavone-induced FASN inhibition and HER2 activation in SKBR3 cells. These results suggest that amentoflavone modulated FASN expression by regulation of HER2-pathways, and induced cell death to enhance chemopreventive or chemotherapeutic activity in HER2-positive breast cancers.

In this study, the effect of the reducibility of the support on the mechanism of the reverse water gas shift reaction over Pt/TiO 2 and Pt/Al 2 O 3 catalysts was examined using a differential and fixed bed reactor. The kinetic study showed that the reverse water gas shift reaction using the Pt/TiO 2 and Pt/Al 2 O 3 catalysts were consistent with the redox mechanism. An elementary reaction test and XPS analysis further confirmed that the reverse water gas shift reaction proceeded through the redox mechanism via oxidation and reduction at the Pt sites and reducible support sites on the catalyst surface. In the H 2 TPR and FT-IR experiments, the Pt/TiO 2 was shown to have a new active site located at the metal–support interface. Therefore, the Pt/TiO 2 catalyst produced greater CO 2 conversion and TOFs due to the presence of the new active site, which resulted from the strong metal–support interaction and higher reducibility of the support relative to the Pt/Al 2 O 3 catalyst.

From a survey of 14 flavonoids of 19 Asian taxa of Fraxinus, flavonols were present in most taxa of sects. Ornus, Fraxinus, and Sciadanthus, while flavones were only detected in Fraxinus lanuginosa in Japan and Fraxinus hopeiensis in China of sect. Ornus and Fraxinus chiisanensis in Korea (as incertae sedia sensu Wallander). The present data failed to clearly distinguish many taxa within the genus because of the extreme monotony of flavonoid content. However, the dichotomy on a smaller scale was observed in Fraxinus, where this chemical approach was useful in the determination of natural groupings of the overlooked taxon F. hopeiensis in China, F. lanuginosa in Japan, and F. chiisanensis in Korea. The gain of O-flavone appears to be a significant evolutionary step; however, the sporadic occurrence of O-flavone in some species is the result of chemical advancement. The present study demonstrated that flavonoid chemistry may indeed be as variable as the morphological features, with no significant flavonoid differences observed at the species level. However, F. hopeiensis, found in the mountain regions of Hebei in northern China, has petals like Fraxinus sieboldiana and F. lanuginosa and is clearly different from other related taxa, including Fraxinus rhynchophylla and Fraxinus chinensis. This study shows that F. hopeiensis is morphologically, chemically, and geographically distinct and should be treated as a distinct species.

Undetected micrometastasis may play a key role in the early relapse of colorectal cancer (CRC) patients. The aim of this study was to detect circulating tumor cells (CTCs) for predicting early relapse of CRC patients by a weighted enzymatic chip array (WEnCA) and analyze 15 candidate genes associated with CRC carcinogenesis. The genes of 105 postoperative CRC patients were analyzed by membrane array and direct sequencing. We constructed a WEnCA platform including five prognosis-related genes and analyzed the detection rate of WEnCA for CTCs in 30 clinically confirmed CRC relapse patients. Postoperative relapse was significantly correlated with gene overexpression, including EVI2B (p=0.001, OR=4.622), ATP2A2 (p=0.006, OR=4.688), S100B (p=0.001, OR=11.521), TM4SF3 (p=0.001, OR=6.756), and OLFM4 (p=0.008, OR=3.545). Using WEnCA (weighting score of each gene: 5 to EVI2B, 5 to ATP2A2, 12 to S100B, 7 to TM4SF3, and 4 to OLFM4), we could detect CTCs presenting these genotypes in relapsed CRC patients. The sensitivity, specificity, and accuracy were 94.7%, 93.5%, and 97%, respectively. The results of the present study suggest that EVI2B, ATP2A2, S100B, TM4SF3, and OLFM4 could be potential prognostic markers for CRC patients.

AMP-activated protein kinase (AMPK) is a sensor of cellular energy status found in all eukaryotes. Recent studies indicate that AMPK activation strongly suppresses cell proliferation in tumor cells, which requires high rates of protein synthesis and de novo fatty acid synthesis for their rapid growth. Pomolic acid (PA) has been previously described as being active in inhibiting the growth of cancer cells. In this study, we investigated PA activated AMPK, and this activity was related to proliferation and apoptosis in MCF7 breast cancer cells. PA inhibited cell proliferation and induced sub-G(1) arrest, elevating the mRNA levels of the apoptotic genes p53 and p21. PA activated caspase-3, -9, and poly(ADP-ribose) polymerase, and this effect was inhibited by z-VAD-fmk. AMPK activation was increased by treating cells with PA, inactivated by treating cells with a compound C, and co-treatment consisting of PA and aminoimidazole carboxamide ribonucleotide (AICAR) synergistically activated AMPK. These anti-cancer potentials of PA were accompanied by effects on de novo fatty acid synthesis as shown by the decreased expression of fatty acid synthase, and decreased acetyl-CoA carboxylase activation and incorporation of [(3)H]acetyl-CoA into fatty acids. In addition, PA inhibited key enzymes involved in protein synthesis such as mammalian target of rapamycin (mTOR), 70 kDa ribosomal protein S6 kinase (p70S6K), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1). These results suggest that PA exerts anti-cancer properties through the modulation of AMPK pathways and its value as an anti-cancer agent in breast cancer therapy.

The Acer wilsonii complex including A. wilsonii, A. tutcheri, and A. confertifoilum is distributed in southern China. Morphological variation was examined to delimit the species and to determine whether recognition at the specific level was warranted. Univariate and bivariate statistical methods, based on data taken from herbarium specimens, were used to examine morphological variation between and within species. This study showed that A. tutcheri differed from A. wilsonii by its rather short inflorescence, small leaf blades, and three leaf lobes with distinctive serrate leaf lobes. In contrast, there was virtually no separation of taxa with respect to the paniculatecorymbose or short paniculate inflorescence between A. confertifolium and A. tutcheri, suggesting that A. confertifolium morphologically resembled A. tutcheri and is a rather smaller form of it. Circumscription of Acer wilsonii has been quite troublesome, because the important holotype and isotype specimens contained different species under the same number and were misleading with respect to the correct application of the name. Furthermore, lobation is very weak within ser. Sinensia, but diversified inflorescences usually occur in China. A three lobed leaves species, A. wilsonii, represents the reduction in lobation without any modification of panicle inflorescences and seems to be closely related to A. sinense. However, A. tutcheri, which shows a reduction in panicle inflorescence with four petals and sepals, may not be closely related to A. sinense. Three lobed taxa may not correctly reflect the true relationship within ser. Sinensia. The designated lectotype of A. wilsonii, line drawings of representative leaves of related species, a key, and distribution maps of these taxa are presented.

Circadian clock genes use transcriptional-translational feedback loops to control circadian rhythms. Recent studies have demonstrated that expression of some circadian clock genes displays daily oscillation in peripheral tissues including peripheral blood and bone marrow. Circadian rhythms regulate various functions of human body, and the disruption of circadian rhythm has been associated with cancer development and tumor progression. However, the direct links between aberrant circadian clock gene expression and human disorders remain largely unknown. In this study, comparisons were made between the expression profiles of 9 circadian clock genes from peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) from 18 healthy volunteers. Peripheral blood (PB) total leukocytes from 54 healthy volunteers and 95 patients with chronic myeloid leukemia (CML) were also investigated. Similar expression profiles of all 9 circadian clock genes were observed in PBMCs and PMNs of healthy individuals. In PB total leukocytes of healthy individuals, the daily pattern of PER1, PER2, PER3, CRY1, CRY2, and CKIε expression level peaked at 0800 h, and BMAL1 peaked at 2000 h. Daily pattern expression of these 7 genes was disrupted in newly diagnosed pre—imatinib mesylate—treated and blast crisis—phase patients with CML. Partial daily pattern gene expression recoveries were observed in patients with CML with complete cytogenetic response and major molecular response. The expression of CLOCK and TIM did not show a time-dependent variation among the healthy and patients with CML. These results indicate a possible association of the disrupted daily patterns of circadian clock gene expression with the pathogenesis of CML.

One new taxon, Alnus incana subsp. tchangbokii Chin S. Chang & H. Kim is described and illustrated here. It is distinguished from its nearest relative, A. incana subsp. hirsuta by having long and large infructescence, broadly rounded leaf base, large terminal bud and fissured bark. A. incana subsp. tchangbokii is known from the mountainous regions of Gyeonggi-do Province, where it grows in deciduous forest montane closed primary forests along ridges at elevations of 200–300 m, while in southern Korea, it is confined to higher altitudes (1000–1300m). Examination of collected specimens suggests A. incana subsp. tchangbokii, be recognized as a subspecies level. An updated key to the four Korean species of Alnus is provided.

We report an unrecorded species of the genus Sorbaria (Rosaceae) in Korea, namely Sorbaria kirilowii (Regel & Tiling) Maxim. This plant was discovered both on Pocheon-si, Naecheon-myeon and Yeoju-gun, Buknae-myeon in Gyeonggi Province. It is distinguishable from Sorbaria sorbifolia (L.) A. Braun var. stellipila Maxim. by characteristics such as presence of hair on leaf and rachis, morphology of inflorescence, length and width of petal, shape of sepal, number and length of stamens, presence of hair upon and size of follicles. This taxon was given the Korean common name 'om-swi-ttang-na-mu'based on the small size of floral characters.

Chemotherapy is an important postsurgery adjuvant therapy in the treatment of breast cancer. However, because of the individual genotype differences of patients, the drug efficacy differs from person to person, even when the same chemotherapy drug is administered. The purpose of this research was to probe the gene expression profiles to predict the efficacy of 5-fluorouracil (5-FU), the common drug used in chemotherapy for various type of cancers, in Taiwanese breast cancer patients. Microarray analysis was conducted on the cancer cell line ZR-75-1 with and without 5-FU stimulation to identify the differentially expressed genes. The significant overexpressed gene groups were selected after bioinformatics software analysis to explore the molecular mechanism of 5-FU. Six strains of breast cancer cell line purchased from American Type Culture Collection were used to analyze the expression profiles of the above target gene groups. IL18, CCL28, CXCL2, SOD1, HRAS, FDXR, and CHI3L1 genes were significantly differentially expressed in 5-FU responder and nonresponder cell lines. The selected gene groups were validated with 20 strains of breast cancer primary cultures established previously in our laboratory. The experimental results demonstrated that FAM46A, IL18, CCL28, TNF, CXCL2, PLEKHA8, HRAS, FDXR, and CHI3L1 genes showed statistically significant differential expression between primary breast cancer culture cells that respond and nonrespond to 5-FU. Six genes, IL18, CCL28, CXCL2, HRAS, FDXR, and CHI3L1, showed significant differential expression pattern in both American Type Culture Collection and primary breast cancer cultured cells. The findings of this study may serve as basis for predicting the effectiveness of 5-FU on breast cancer.

Reproductive activities of salmonids are synchronized by changes in photoperiod, which control the endocrine system via the brain-pituitary-gonadal axis. Gonadotropin-releasing hormone (GnRH) in the brain regulates synthesis and release of the pituitary gonadotropins (GTHs; FSH and LH). FSH and LH in turn stimulate the production of sex steroids for oocyte growth and maturation-Inducing steroid hormones for oocyte maturation and ovulation, respectively, in female salmonids. To clarify effects of long-term photoperiod manipulations on the reproductive activity of salmonids from early recrudescence to ovulation, we Investigated the gene expression profiles of GnRH, GTHs, and vitellogenin (VTG), and plasma sex steroids in female rainbow trout (Oncorhynchus mykiss). In addition, the percentages of eyed embryos and hatched alevins were examined together with the number of ovulated eggs to evaluate the effects of photoperiod regimes on egg quality. During late summer, the mRNA levels of GnRHs, GTHalpha, and LHbeta, and the plasma level of a maturational steroid (17alpha,20beta-dihydroxy-4-pregnen-3-one; 17,20beta-P) were significantly elevated by a gradually shortened photoperiod under constant temperature, in accordance with accelerated sexual maturation. The percentages of eyed embryos and hatched alevins from fish ovulated in August were comparable to those of control fish observed in December. These results clearly indicate that syntheses of GnRHs, LH, VTG, and 17,20beta-P are effectively accelerated by a programmed long-short photoperiod regime in early recrudescent female rainbow trout, without a marked deterioration in egg quality.

Background Janus kinase 2 (JAK2) is a tyrosine kinase involved in the cytokine signaling of several growth factors such as erythropoietin and thrombopoietin in normal and neoplastic cells. The G to T exchange at nucleotide 1849 in exon 14 of the JAK2 gene leads to a substitution of valine with phenylalanine at the amino acid position 617 (V617F) of the JAK2 protein. Currently, the occurrence of the JAK2 V617F mutation is well recognized in chronic myeloproliferative disorders (MPDs). Methods We identified JAK2 V617F missense mutation in patients with MPD by high resolution melting (HRM) analysis. HRM analysis is a new gene scan tool that quickly performs the PCR and identifies sequences alterations without requiring post-PCR treatment. This study included 7 PV patients (41.1%), 6 ET patients (35.3%), and 4 myelofibrosis patients (23.5%). Additionally, our methodology was compared with amplification refractory mutation system (ARMS) assay. Results Up to 5% of the JAK2 V617F mutation was successfully detected in patients with MPD using HRM analysis. Eleven out of 17 patients (64.7%) were positive for the presence of JAK2 V617F mutation. The prevalence of mutation in the different subtypes of MPDs was 85.7% in PV (6 of 7 patients), 66.7% in ET (4 of 6) and 5.9% in myelofibrosis (1 of 4). The results proved 100% comparable to those obtained by ARMS assay. Conclusions The HRM analysis is a rapid and effective technique for the detection of JAK2 V617F missense mutation.

Sambucus pendula Nakai, which is an endemic on Ulleung Island of Korea, is characterized by a large pendulous inflorescence and small fruit. A set of 256 individuals were used to investigate the patterns of intraspecific variation of S. racemosa subsp. kamtchatica, S. racemosa subsp. sieboldiana, and S. williamsii including S. pendula using PCA (principal components analysis). This analysis showed that S. pendula was distinct based on its large inflorescence and long peduncle. Our data showed a morphological distinction between subsp. kamtchatica from northeastern areas and subsp. sieboldiana from Jeju Island, but the two taxa overlap in the southern and eastern parts of Korea in terms of chromosome number, color of style, and allozyme data. Our study agrees that S. pendula on Ulleung Island may be the result of genetic drift that occurred during isolation since the Quarternary period. This has been suggested as a reason for the genetic differences observed between two taxa and would explain the unique variation patterns of S. pendula. However, the morphological differentiation between the S. racemosa complex and S. pendula is not considered sufficient to warrant recognition of specific status. Therefore, we recommend that only one polymorphic species of S. racemosa in Eurasia be recognized and that S. pendula be considered a subspecies of S. racemosa.

Type 2 diabetes mellitus (T2DM) is a polygenetic disease. Its incidence is increasing continuously in Taiwan as the standard of living improves. Current diabetes research is striving to identify those high at risk of T2DM through T2DM- associated gene studies. A number of techniques are available for the molecular detection of T2DM-associated genes, including polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), direct sequencing, and TaqMan genotyping. However, they are capable of analyzing only one molecular target in each experiment. In the present study, we selected eight candidate genes that are potentially associated with T2DM [angiotensinogen (AGT), sulfonylurea receptor-1 (SUR-1), peroxisome proliferators-activated receptor-γ (PPAR-γ), PPAR-γ coactivator-1 (PGC-1), calpain-10 (CAPN10), β2-adrenergic receptor (ADRB2), mannose-binding lectin (MBL2), and insulin receptor substrate-1 (IRS-1)]. We used enzymatic chip array technology, which we had previously established, and analyzed its relevance to diabetes research. We enrolled 1280 Taiwanese patients (700 with T2DM and 580 non-diabetic controls). The genes of all subjects were analyzed by the enzymatic chip array. The results were consistent with direct sequencing. On the basis of multivariate logistic-regression analysis—with adjustment for age—the following variables were associated with a significant risk of T2DM: body mass index, serum cholesterol, triglyceride level, low- and high-density lipoprotein cholesterol levels, and polymorphisms, including PGC-1 Gly482Ser, SUR1 Arg1273Arg, ADRB2 Arg16Gly, CAPN10 SNP43, AGT Met235Thr, and MLB2 Gly54Asp. The enzymatic chip array is a useful tool for multiple gene analysis in diabetes.

Potentio-dynamic polymerization of buffered urease and pyrrole monomer onto carbon papers was conducted to fabricate an immobilized urease electrode for measuring the urea concentration. To use carbon paper as the substrate for the electro-growth of polypyrrole matrix not only created sufficient adhesion of the conducting polymer layer but also provided superior entrapment of urease enzymes. The potentiometric response corresponding to ammonia, the product formed from the urease catalyzed urea reaction, was employed for the urea concentration measurement. Scanning electron microscopic photographs showed that the polypyrrole matrix deposited on the carbon papers appeared to be of a cylindrical nanotube shape. The charge density applied in the polymerization was found to affect the potentiometric response while the potential-scanning rate showed minor influence. The composite electrodes had high sensitivity in urea detection, showing a response linear to the logarithm of the urea concentration in the range of 10(-3) to 10 mM. The detection of urea solution prepared in water and buffer was also compared. Ionic effect on the sensing of urea solution was investigated. By comparing the data reported in literature, the urease/polypyrrole/carbon paper electrode developed in this work showed superior long-term stability and reusability. The detection of urea in serum was also well performed.

Although manganese (Mn) has been shown to increase prolactin (PRL) by decreasing dopamine (DA) in the hypothalamus, the mechanism of Mn-induced regulation of the hypothalamic-hypophyseal-pituitary axis is unclear. We assessed the effects of inhaled Mn on hypothalamic DA and pituitary PRL production and evaluated the role of pituitary-specific transacting factor 1 (Pit-1), a transacting factor of PRL gene, in Mn-induced changes in PRL secretion in the rat brain. Male rats exposed to Mn for 4 or 13 weeks (1.5 mg/m3, 6 h/day, 5 days/week) showed a progressive and significant decrease in hypothalamic DA, whereas PRL and Pit-1 mRNA levels increased in response to Mn exposure. These results suggest that exposure to Mn decreases hypothalamic DA and promotes the production of PRL in the pituitary and that Pit-1 might be a regulator of DA and PRL.

Extracts derived from various medical mushrooms have been reported to have antitumor and immuno‐modulatory properties. In order to investigate the antitumor activity of keumsa Linteusan, the water extract of Phellinus limteus, HT1080 cells, a human fibrosarcoma cell line, were treated with it and changes in cellular migration potential was tested in vitro. At a concentration range below 1,000 μg/ mL, Linteusan blocked, in a dose dependent manner, the migration of cells through Matrigel as well as Boyden chamber without affecting the viability of the cells. Prolonged treatment of HT1080 cells with Linteusan suppressed TNF‐a induced production of matrix metalloproteinase (MMP)‐9 as well as basal level expression of MMP‐2. Linteusan also affected the adhesion of the cells to fibronectin‐coated surfaces. The effect of Linteusan on cell signaling pathways was also tested. Linteusan specifically affected TNF‐α induced phosphorylation of AKT in a dose‐dependent manner, while phosphorylation levels of ER...

Invariant NKT (iNKT) cells are a distinct subset of T lymphocytes that recognize glycolipid Ags. Upon TCR stimulation, iNKT cells promptly secrete a wide range of cytokines and therefore have been investigated as a target for immunotherapy. However, after primary activation, iNKT cells become hyporesponsive toward their ligand (anergy). The further mechanism behind iNKT cell anergy is poorly understood. We found that a low level of programmed death-1 (PD-1) was constitutively expressed on iNKT cells and that PD-1 expression was increased after stimulation and lasted at least 2 mo. Moreover, not only did blocking of the PD-1/PD ligand 1 (PD-L1) pathway prevent the induction of anergy in iNKT cells, but anergic iNKT cells also recovered responsiveness and these “rescued” cells efficiently mediated antitumor immunity. Our findings suggest that the PD-1/PD-L1 interaction is essential for the induction and maintenance of iNKT cell anergy.

Molecular genotyping of the ABO alleles has been widely used in ABO subgroups analysis and has been able to solve the rare ABO blood grouping discrepancies. The genotypes of sixty-one A2B phenotype donors recruited from the middle and south of Taiwan were analyzed by means of molecular methods. The A2B phenotype was initially identified by serological test. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to screen the ABO alleles at nucleotides (nt) 261 and 703 based on the nt differences found in the ABO alleles. The subgroups of the A2 allele were determined by the PCR-RFLP and direct sequencing methods. The discrepancies between the phenotype and genotype of the A2B were then studied by subcloning and nucleotide sequence analysis. Our results show that 55 of the 61 A2B donors (90%) are A205/B allele and two are A201/B allele. Four cases were heterozygotes of the cis-AB/O or B alleles. Two were cis-AB04/O allele, one was cis-AB01/O allele and the other was cis-AB02/B allele. In conclusion, most A2B genotypes belong to the A205/B allele in Taiwan. In this study, we report for the first time the presence of the A205, A201, and cis-AB02 alleles in Taiwan.

beta-thalassemia major can be caused by homozygosity or compound heterozygosity for beta-globin gene mutations (HBB gene). Most cases are inherited from parents who both have diseased alleles of the HBB gene. We report a patient with late-onset beta-thalassemia major that evolved from beta-thalassemia minor in which only one of her parents had the diseased HBB gene. To study the cause of beta-thalassemia major in this patient, we performed the 100K single nucleotide polymorphism genotyping assay, fluorescence in situ hybridization, and DNA methylation analysis of the imprinting genes near the HBB gene. The results showed a loss of heterozygosity in the region of chromosome 11p14.3 to 11p15.5, which perfectly matched one allele of her father. Our study demonstrates that paternal uniparental isodisomy of chromosomal 11p15.5 is associated with the beta-thalassemia major in this patient. Key words: beta-thalassemia major, uniparental isodisomy, mosaicism.

Flavonoids were isolated and identified from flowers and/or leaves of the Adonis amurensis complex. This complex has been a persistent source of taxonomic confusion due to the exclusive use of continuous variation in flower morphology for species definition and recognition. Nineteen flavonoids, including C‐glycosylflavones, O‐glycosylflavones, and flavonol O‐glycosides were characterized. The flavonoids isolated from flowers and leaves of the A. amurensis complex were not the same. The phenogram indicated three major clusters; A. multiflora, A. ramosa‐A. pseudoamurensis, and A. amurensis. A. amurensis was characterized by a higher flavonoid diversity composed of a variety of C‐glycosylflavones, while A. multiflora was generally characterized by a reduced flavonoid profiles. It is probable that evolutionary advancement is reflected in loss of some of C‐glycosylflavone and all of O‐glycosylflavone synthesis, resulting in A. multiflora within this series. The present study has demonstrated that the flavonoid...

Brassinolide insensitive associated receptor kinase 1(BAK1) is a critical component that play an important roles in signaling of brassinosteroid biosynthesis. Brassinosteroid-deficient and -insensitive mutants showed the characteristic of dwarf symptom. The nutrient deficient tomato showing stunt phenomenon was selected from soiless cultivation system using modified Sonneveld hydroponic solution. Twenty eight protein spots showing different expression levels compared to the control were isolated from extracts of stunted tomato leaves by 2D PAGE analyses. Significantly down-regulated 6 protein spots out of 28 protein spots were analyzed and sequenced by MALDI-TOF mass spectrometry. The protein spot having pI