(π‐Allyl)Pd Complexes Containing N‐Heterocyclic Carbene and Pseudohalogen Ligands – Synthesis, Reactivity toward Organic Isothiocyanates and Isocyanides, and Their Catalytic Activity in Suzuki–Miyaura Cross‐Couplings

Kim, Hyun&#x2010,Kyung,Lee, Jung&#x2010,Hyun,Kim, Yong&#x2010,Joo,Nu Zheng, Zhen,Lee, Soon W. WILEY‐VCH Verlag 2013 European journal of inorganic chemistry Vol.2013 No.28

<P><B>Abstract</B></P><P>Dinuclear (π‐allyl)palladium chlorides, [(π‐allyl)Pd(μ‐Cl)]<SUB>2</SUB>, were cleaved by N‐heterocyclic carbenes (NHCs) to give mononuclear (π‐allyl)palladium–NHC chlorides, [(π‐allyl)Pd(Cl)(NHC)] (<B>1</B>–<B>6</B>) [NHC = 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene (IPR), 1,3‐bis(2,6‐diisopropylphenyl)‐4,5‐dihydroimidazol‐2‐ylidine (SIPR), 1,3‐bis(2,4,6‐trimethylphenyl)imidazol‐2‐ylidene (IMes)]. Complexes <B>1</B>–<B>6</B> were subsequently treated with aqueous NaN<SUB>3</SUB>, KSCN, KOCN, and CF<SUB>3</SUB>COOAg to produce the corresponding mononuclear (π‐allyl)palladium–NHC pseudohalogen complexes, [(π‐allyl)Pd(X)(NHC)] (X = N<SUB>3</SUB>, NCS, SCN, NCO, CF<SUB>3</SUB>COO) (<B>7</B>–<B>30</B>). These products could also be obtained by treating dinuclear pseudohalogen‐bridged Pd complexes, [(π‐allyl)Pd(μ‐X)]<SUB>2</SUB>, which were prepared by replacing the μ‐Cl ligand in [(π‐allyl)Pd(μ‐Cl)]<SUB>2</SUB>, with aqueous NaN<SUB>3</SUB>, KSCN, KOCN, or CF<SUB>3</SUB>COOAg, followed by cleavage with the NHCs. Reactions of [(π‐allyl)Pd(N<SUB>3</SUB>)(NHC)] with organic isothiocyanates (R–NCS) or CH<SUB>3</SUB>O(CO)C≡CO(CO)CH<SUB>3</SUB> resulted in selective 1,3‐dipolar cycloaddition into the Pd–azido bond to give heterocyclic compounds. By contrast, analogous reactions of [(η<SUP>3</SUP>‐allyl)Pd(N<SUB>3</SUB>)(IPr)] with an organic isocyanide (R–NC: R = <I>tert</I>‐butyl, benzyl) gave the adduct [(η<SUP>3</SUP>‐allyl)Pd(N<SUB>3</SUB>)(IPr)]<B>·</B>(R–NC) as the only product or a mixture of the adduct and a dipolar cycloaddition product, [(η<SUP>3</SUP>‐allyl)Pd{CN<SUB>4</SUB>(R)}(IPr)], depending on the isocyanides used. Finally, a series of (π‐allyl)Pd–NHC pseudohalogen complexes, [(π‐allyl)Pd(X)(NHC)], exhibited high catalytic activity in Suzuki–Miyaura cross‐coupling reactions of aryl chlorides with arylboronic acids.</P>

Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis

Yu, K&#x2010,H.,Hong, K&#x2010,S.,Lee, B&#x2010,C.,Oh, M&#x2010,S.,Cho, Y&#x2010,J.,Koo, J&#x2010,S.,Park, J&#x2010,M.,Bae, H&#x2010,J.,Han, M&#x2010,K.,Ju, Y&#x2010,S.,Kang, D&#x2010,W.,Appelros, P. Blackwell Publishing Ltd 2011 Acta neurologica Scandinavica Vol.123 No.5

<P>Yu K‐H, Hong K‐S, Lee B‐C, Oh M‐S, Cho Y‐J, Koo J‐S, Park J‐M, Bae H‐J, Han M‐K, Ju Y‐S, Kang D‐W, Appelros P, Norrving B, Terent A. Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis. 
Acta Neurol Scand: 2011: 123: 325–331. 
© 2010 John Wiley & Sons A/S.</P><P><B>Background – </B> It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case‐fatality between two PSM cohorts of Sweden and Korea.</P><P><B>Methods – </B> Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one‐to‐one matching based on propensity scores of each patient.</P><P><B>Results – </B> After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90‐day case‐fatality was identical 6.2% (HR 0.997, 95%CI 0.905–1.099) in Sweden and Korea.</P><P><B>Conclusions – </B> No difference is found in the 90‐day case‐fatality in propensity score‐matched Swedish and Korean patients with ischemic stroke.</P>

Interference of hepatitis C virus replication in cell culture by antisense peptide nucleic acids targeting the X‐RNA

Ahn, D.&#x2010,G.,Shim, S.&#x2010,B.,Moon, J.&#x2010,E.,Kim, J.&#x2010,H.,Kim, S.&#x2010,J.,Oh, J.&#x2010,W. Blackwell Publishing Ltd 2011 Journal of viral hepatitis Vol.18 No.7

<P><B>Summary. </B> The RNA‐dependent RNA polymerase (RdRp) of hepatitis C virus (HCV) is the essential catalytic enzyme for viral genome replication. It initiates minus‐strand RNA synthesis from a highly conserved 98‐nt sequence, called the X‐RNA, at the 3′‐end of the plus‐strand viral genome. In this study, we evaluated the antiviral effects of peptide nucleic acids (PNAs) targeting the X‐RNA. Our <I>in vitro</I> RdRp assay results showed that PNAs targeting the three major stem‐loop (SL) domains of X‐RNA can inhibit RNA synthesis initiation. Delivery of X‐RNA‐targeted PNAs by fusing the PNAs to cell‐penetrating peptides (CPPs) into HCV‐replicating cells effectively suppressed HCV replication. Electrophoretic mobility shift assays revealed that the PNA targeting the SL3 region at the 5′‐end of X‐RNA dissociated the viral RdRp from the X‐RNA. Furthermore, delivery of the SL3‐targeted PNA into HCV‐infected cells resulted in the suppression of HCV RNA replication without activation of interferon β expression. Collectively, our results indicate that the HCV X‐RNA can be effectively targeted by CPP‐fused PNAs to block RNA–protein and/or RNA–RNA interactions essential for viral RNA replication and identify X‐RNA SL3 as an RdRp binding site crucial for HCV replication. In addition, the ability to inhibit RNA synthesis initiation by targeting HCV X‐RNA using antisense PNAs suggests their promising therapeutic potential against HCV infection.</P>

Epidermal regeneration by <i>ent</i>‐16α, 17‐dihydroxy‐kauran‐19‐oic acid isolated from <i>Siegesbeckia pubescens</i>

Sung, S.&#x2010,H.,Park, S.&#x2010,H.,Song, S.&#x2010,Y.,Lee, S.&#x2010,J.,Lee, H.&#x2010,W.,Kim, S.&#x2010,H.,A Lee, M.,Yoon, I.&#x2010,S.,Kim, D.&#x2010,D.,Kang, S.,Sung, J.&#x2010,H. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.6

<P><B>Abstract</B></P><P><B>Objectives: </B> Keratinocyte stem/progenitor cells (KSCs) are known to regenerate epidermal tissue which they perform through to their great regenerative capacity.</P><P><B>Materials and methods: </B> Because stimulation of resident KSCs may regenerate epidermal tissue, we devised a strategy to find an appropriate KSC activator from natural products and to develop it as a skin‐rejuvenating agent.</P><P><B>Results: </B> <I>Ent</I>‐16α, 17‐dihydroxy‐kauran‐19‐oic acid (DHK) isolated from <I>Siegesbeckia pubescens</I> exhibited a KSC‐stimulating effect during screening of natural products. DHK increased proliferation and migration of KSCs using the Akt/ERK pathway. We further examined the mechanism of KSC stimulation and found that phosphorylation of Y1068 epithelial growth factor receptor (EGFR) was significantly increased. Functional inhibition of EGFR using neutralizing antibody and a chemical inhibitor, AG1478, attenuated DHK‐induced KSC stimulation. In a 3D culture model of KSCs, DHK treatment significantly induced establishment of fully stratified epidermis and increased numbers of p63‐positive cells. Likewise, DHK treatment significantly accelerated healing of epidermal wounds created by laser and dermatome, and increased p63‐positive cells, in animal models.</P><P><B>Conclusion: </B> Collectively, these results indicate that DHK regenerates epidermal tissue mainly through EGFR phosphorylation. As DHK has diverse advantages over recombinant growth factors for commercialization (that is long‐term stability and skin permeability), DHK might be applied to wound‐healing agents and to a basic materials used in cosmetics.</P>

Serum Adipokine Concentrations in Dogs with Acute Pancreatitis

Paek, J.,Kang, J.&#x2010,H.,Kim, H.&#x2010,S.,Lee, I.,Seo, K.W.,Yang, M.&#x2010,P. John Wiley and Sons Inc. 2014 Journal of veterinary internal medicine Vol.28 No.6

<P><B>Background</B></P><P>Limited information is available about the role of adipokines in the development and progression of acute pancreatitis (AP) in dogs.</P><P><B>Objectives</B></P><P>To determine whether the circulating concentrations of adipokines differed between healthy dogs and dogs with AP, and whether the circulating concentrations differed between AP survivors and AP nonsurvivors.</P><P><B>Animals</B></P><P>Twenty‐eight healthy dogs and 25 client‐owned dogs with AP.</P><P><B>Methods</B></P><P>Prospective observational cohort study of 25 client‐owned dogs with newly diagnosed AP and 28 otherwise healthy dogs with similar body condition scores. The serum concentrations of leptin, adiponectin, resistin, visfatin, interleukin (IL)‐1β, IL‐6, IL‐10, IL‐18, and tumor necrosis factor (TNF)‐α were measured.</P><P><B>Results</B></P><P>The serum concentrations of leptin (<I>P </I>=<I> </I>.0021), resistin (<I>P </I>=<I> </I>.0010), visfatin (<I>P </I><<I> </I>.0001), IL‐1β (<I>P </I><<I> </I>.0001), IL‐6 (<I>P </I>=<I> </I>.0002), IL‐10 (<I>P </I><<I> </I>.0001), and IL‐18 (<I>P </I><<I> </I>.0001) were significantly higher in dogs with AP than healthy dogs, whereas the adiponectin concentration (<I>P </I>=<I> </I>.0011) was significantly lower. There were significant differences in the serum concentrations of leptin (<I>P </I>=<I> </I>.028) and adiponectin (<I>P </I>=<I> </I>.046) in survivors and nonsurvivors. After the disappearance of clinical signs, the concentrations of resistin (<I>P </I>=<I> </I>.037) and IL‐1β (<I>P </I>=<I> </I>.027) decreased significantly, whereas the serum concentrations of leptin (<I>P </I>><I> </I>.999), adiponectin (<I>P </I>=<I> </I>.11), visfatin (<I>P </I>=<I> </I>.83), IL‐6 (<I>P </I>=<I> </I>.82), IL‐10 (<I>P </I>=<I> </I>.82), IL‐18 (<I>P </I>=<I> </I>.56), and TNF‐α (<I>P </I>=<I> </I>.94) did not differ significantly.</P><P><B>Conclusion and Clinical Importance</B></P><P>This study showed that dysregulation of adipokines might be involved in the pathogenesis of AP. In addition, leptin and adiponectin are likely to be associated with mortality rate in AP.</P>

Molecular genetic diversity and population structure of a selected core set in garlic and its relatives using novel SSR markers

Zhao, W.&#x2010,G.,Chung, J.&#x2010,W.,Lee, G.&#x2010,A.,Ma, K.&#x2010,H.,Kim, H.&#x2010,H.,Kim, K.&#x2010,T.,Chung, I.&#x2010,M.,Lee, J.&#x2010,K.,Kim, N.&#x2010,S.,Kim, S.&#x2010,M.,Park, Y.&#x2010 Blackwell Publishing Ltd 2011 Plant breeding Vol.130 No.1

<P> <I>With 7 figures and 6 tables</I> </P><P><B>Abstract</B></P><P>Garlic is widely consumed for its culinary and medical benefits. Six hundred and thirteen accessions of garlic and its relatives with diverse origin were evaluated for genetic diversity at eight recently novel simple sequence repeat loci in this study. A total of 113 alleles were detected, the average allelic richness was 14.1 alleles per locus. Using a heuristic approach, a core set of 95 accessions was successfully developed, which showed 100% coverage of alleles with minimum redundancy. The model‐based structure analysis here revealed the presence of four subpopulations in the selected core set, which was basically consistent with clustering based on the genetic distance. The analysis of molecular variance based on this core set showed that between‐population component of genetic variance is <15.6% in contrast to 84.4% for the within population component. Overall <I>F</I><SUB>ST</SUB> value was 0.1560, indicating a moderate differentiation among the four groups. These results will provide an effective aid for future allele mining, association genetics, mapping and cloning gene(s), germplasm conservation, and improvement programs.</P>

The multiple merger assembly of a hyperluminous obscured quasar at redshift 4.6

Di&#x301,az-Santos, T.,Assef, R. J.,Blain, A. W.,Aravena, M.,Stern, D.,Tsai, C.-W.,Eisenhardt, P.,Wu, J.,Jun, H. D.,Dibert, K.,Inami, H.,Lansbury, G.,Leclercq, F. American Association for the Advancement of Scienc 2018 Science Vol.362 No.6418

<P><B>Mergers drive a powerful dusty quasar</B></P><P>Massive galaxies in the early Universe host supermassive black holes at their centers. When material falls toward the black hole, it releases energy and is observed as a quasar. Astronomers found a population of powerful distant quasars that are obscured by dust, but it has been unclear how they are formed. Díaz-Santos <I>et al.</I> observed the dust-obscured quasar WISE J224607.56-052634.9 at submillimeter wavelengths, finding three small companion galaxies connected to the quasar by bridges of gas and dust. They inferred that galaxy mergers can provide both the raw material to power a quasar and large quantities of dust to obscure it.</P><P><I>Science</I>, this issue p. 1034</P><P>Galaxy mergers and gas accretion from the cosmic web drove the growth of galaxies and their central black holes at early epochs. We report spectroscopic imaging of a multiple merger event in the most luminous known galaxy, WISE J224607.56−052634.9 (W2246−0526), a dust-obscured quasar at redshift 4.6, 1.3 billion years after the Big Bang. Far-infrared dust continuum observations show three galaxy companions around W2246−0526 with disturbed morphologies, connected by streams of dust likely produced by the dynamical interaction. The detection of tidal dusty bridges shows that W2246−0526 is accreting its neighbors, suggesting that merger activity may be a dominant mechanism through which the most luminous galaxies simultaneously obscure and feed their central supermassive black holes.</P>

Association of Obesity with Serum Leptin, Adiponectin, and Serotonin and Gut Microflora in Beagle Dogs

Park, H.&#x2010,J.,Lee, S.&#x2010,E.,Kim, H.&#x2010,B.,Isaacson, R.E.,Seo, K.&#x2010,W.,Song, K.&#x2010,H. John Wiley and Sons Inc. 2015 Journal of veterinary internal medicine Vol.29 No.1

<P><B>Background</B></P><P>Serotonin (5‐hydroxytryptamine, 5HT) is involved in hypothalamic regulation of energy consumption. Also, the gut microbiome can influence neuronal signaling to the brain through vagal afferent neurons. Therefore, serotonin concentrations in the central nervous system and the composition of the microbiota can be related to obesity.</P><P><B>Objective</B></P><P>To examine adipokine, and, serotonin concentrations, and the gut microbiota in lean dogs and dogs with experimentally induced obesity.</P><P><B>Animals</B></P><P>Fourteen healthy Beagle dogs were used in this study.</P><P><B>Methods</B></P><P>Seven Beagle dogs in the obese group were fed commercial food ad libitum, over a period of 6 months to increase their weight and seven Beagle dogs in lean group were fed a restricted amount of the same diet to maintain optimal body condition over a period of 6 months. Peripheral leptin, adiponectin, 5HT, and cerebrospinal fluid (CSF‐5HT) levels were measured by ELISA. Fecal samples were collected in lean and obese groups 6 months after obesity was induced. Targeted pyrosequencing of the 16S rRNA gene was performed using a Genome Sequencer FLX plus system.</P><P><B>Results</B></P><P>Leptin concentrations were higher in the obese group (1.98 ± 1.00) compared to those of the lean group (1.12 ± 0.07, <I>P</I> = .025). Adiponectin and 5‐hydroytryptamine of cerebrospinal fluid (CSF‐5HT) concentrations were higher in the lean group (27.1 ± 7.28) than in the obese group (14.4 ± 5.40, <I>P</I> = .018). Analysis of the microbiome revealed that the diversity of the microbial community was lower in the obese group. Microbes from the phylum Firmicutes (85%) were predominant group in the gut microbiota of lean dogs. However, bacteria from the phylum Proteobacteria (76%) were the predominant group in the gut microbiota of dogs in the obese group.</P><P><B>Conclusions and Clinical Importance</B></P><P>Decreased 5HT levels in obese group might increase the risk of obesity because of increased appetite. Microflora enriched with gram‐negative might be related with chronic inflammation status in obese dogs.</P>

Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II

Lee, K&#x2010,E,Kang, H&#x2010,Y,Lee, S&#x2010,K,Yoo, S&#x2010,H,Lee, J&#x2010,C,Hwang, Y&#x2010,H,Nam, KH,Kim, J&#x2010,S,Park, J&#x2010,C,Kim, J&#x2010,W Blackwell Publishing Ltd 2011 Clinical genetics Vol.79 No.4

<P>Lee K‐E, Kang H‐Y, Lee S‐K, Yoo S‐H, Lee J‐C, Hwang Y‐H, Nam KH, Kim J‐S, Park J‐C, Kim J‐W. Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II.</P><P>The dentin sialophosphoprotein (<I>DSPP</I>) gene encodes the most abundant non‐collagenous protein in tooth dentin and DSPP protein is cleaved into several segments including the highly phosphorylated dentin phosphoprotein (DPP). Mutations in the <I>DSPP</I> gene have been solely related to non‐syndromic form of hereditary dentin defects. We recruited three Korean families with dentinogenesis imperfecta (DGI) type II and sequenced the exons and exon–intron boundaries of the <I>DSPP</I> gene based on the candidate gene approach. Direct sequencing of PCR products and allele‐specific cloning of the highly repetitive exon 5 revealed novel single base pair (bp) deletional mutations (c.2688delT and c.3560delG) introducing hydrophobic amino acids in the hydrophilic repeat domain of the DPP coding region. All affected members of the three families showed exceptionally rapid pulp chambers obliteration, even before tooth eruption. Individuals with the c.3560delG mutation showed only mild, yellowish tooth discoloration, in contrast to the affected individuals from two families with c.2688delT mutation. We believe that these results will help us to understand the molecular pathogenesis of DGI type II as well as the normal process of dentin biomineralization.</P>

Serine palmitoyltransferase inhibitor myriocin induces growth inhibition of B16F10 melanoma cells through G₂/M phase arrest

Lee, Y.&#x2010,S.,Choi, K.&#x2010,M.,Choi, M.&#x2010,H.,Ji, S.&#x2010,Y.,Lee, S.,Sin, D.&#x2010,M.,Oh, K.&#x2010,W.,Lee, Y.&#x2010,M.,Hong, J.&#x2010,T.,Yun, Y.&#x2010,P.,Yoo, H.&#x2010,S. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.4

<P><B>Abstract</B></P><P><B>Objectives: </B> Melanoma is the most aggressive form of skin cancer, and it resists chemotherapy. Candidate drugs for effective anti‐cancer treatment have been sought from natural resources. Here, we have investigated anti‐proliferative activity of myriocin, serine palmitoyltransferase inhibitor, in the <I>de novo</I> sphingolipid pathway, and its mechanism in B16F10 melanoma cells.</P><P><B>Material and methods: </B> We assessed cell population growth by measuring cell numbers, DNA synthesis, cell cycle progression, and expression of cell cycle regulatory proteins. Ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate levels were analysed by HPLC.</P><P><B>Results: </B> Myriocin inhibited proliferation of melanoma cells and induced cell cycle arrest in the G<SUB>2</SUB>/M phase. Expressions of cdc25C, cyclin B1 and cdc2 were decreased in the cells after exposure to myriocin, while expression of p53 and p21<SUP>waf1/cip1</SUP> was increased. Levels of ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate in myriocin‐treated cells after 24 h were reduced by approximately 86%, 57%, 75% and 38%, respectively, compared to levels in control cells.</P><P><B>Conclusions: </B> Our results suggest that inhibition of sphingolipid synthesis by myriocin in melanoma cells may inhibit expression of cdc25C or activate expression of p53 and p21<SUP>waf1/cip1</SUP>, followed by inhibition of cyclin B1 and cdc2, resulting in G<SUB>2</SUB>/M arrest of the cell cycle and cell population growth inhibition. Thus, modulation of sphingolipid metabolism by myriocin may be a potential target of mechanism‐based therapy for this type of skin cancer.</P>