Antimicrobial cellulose acetate nanofibers containing silver nanoparticles

It was found for the first time that polymer nanofibers containing Ag nanoparticles on their surface could be produced by UV irradiation of polymer nanofibers electrospun with small amounts of silver nitrate (AgNO₃). When the cellulose acetate (CA) nanofibers electrospun from CA solutions with 0.5 wt% of AgNO₃ were irradiated with UV light at 245 nm, Ag nanoparticles were predominantly generated on the surface of the CA nanofibers. The number and size of the Ag nanoparticles were continuously increased up to 240 min. The Ag⁺ ions and Ag clusters diffused and aggregated on the surface of the CA nanofibers during the UV irradiation. The Ag nanoparticles with an average size of 21 nm exhibited strong antimicrobial activity.     

Satellite cells isolated from adult Hanwoo muscle can proliferate and differentiate into myoblasts and adipose-like cells

This study examined whether adult bovine muscle satellite cells from 30-month-old Hanwoo cattle are multipotential. The satellite cells were found to have the potential to proliferate and differentiate into myoblasts with the formation of multinucleated cells. In addition, treatment with the peroxisome proliferator activating receptor-gamma (PPARgamma) agonist, rosiglitazone, promoted their trans-differentiation into adipocytes with significant increases in glycerol accumulation and glycerol-3-phosphate dehydrogenase activity. Western blot analysis revealed that increased levels of the adipocyte fatty acid-binding protein, PPARgamma and of CCAAT/enhancer-binding protein were closely related to rosiglitazone-induced differentiation of the cells. These findings demonstrate that satellite cells from adult Hanwoo cattle are multipotent, and that their trans-differentiation into adipocytes can be induced by rosiglitazone.     

HydroKorea and CarboKorea: cross-scale studies of ecohydrology and biogeochemistry in a heterogeneous and complex forest catchment of Korea

The KoFlux program is dedicated to understanding the fluxes of energy and matter, water resource management, and net ecosystem production in key ecosystems of Monsoon Asia. Under the framework of AsiaFlux, it is a joint effort with determined, comprehensive international strategies to bring Asia’s key ecosystems under observation. Built upon the augmented KoFlux infrastructure (i.e., Gwangneung supersite), the ‘HydroKorea’ and ‘CarboKorea’ projects pursue new methodologies to assess water and carbon cycles at various temporal, spatial, and process scales. Particularly, the multiscaling approaches are used to link process-level studies, flux footprint, ecohydrological and biogeochemical schemes, and high-resolution satellite images. We hope that the work presented here encourages more ground-breaking studies aimed at bridging the gaps in the cross-scale studies of ecohydrological and biogeochemical cycles in heterogeneous and complex landscapes.     

The prolonged half-lives of new erythropoietin derivatives via peptide addition

Erythropoietin, or Epo, is a hematopoietic cytokine that promotes erythropoiesis, and recombinant human Epo has been used in the treatment of anemia in various chronic diseases. Here, we have constructed novel Epo derivatives with prolonged half-lives by adding peptides to the carboxy terminus of Epo without using linkers. The fused peptides were selected from the carboxy terminal region of human chorionic gonadotropin (hCG) or human thrombopoietin (hTpo), which promote the proper folding, secretion, and stabilization of bioactive glycoproteins. Addition of these peptides did not interfere with secretion or receptor binding, and significantly increased the in vivo half-life of human Epo, as measured by intravenous administration in rats. The plasma half-life of the Epo constructs was longest when the carboxy terminal 28 aa of the beta subunit of hCG was added (Epo-CGC), a half-life that was slightly longer than NESP (Aranesp), which is the most effective Epo product in current clinical use. The transformation of four Ser glycosylation sites to Ala on the CGC sequence also lengthened the plasma half-life of Epo, indicating that the in vivo stabilizing effect of the hCG peptide was due to both structures within the peptide itself and its O-glycosylations. The application of the carboxy terminal half of hTpo also resulted in remarkably reduced elimination of the Epo chimera (Epo-TpC), possibly due to protection by the TpC sequence. The in vivo hematopoietic activity of Epo derivatives in mice was consistent with their pharmacokinetic profiles. Therefore, these derivatives with prolonged half-lives may provide opportunities for developing new Epo therapeutics with less frequent administration.     

Liquid chromatography-tandem mass spectrometric determination of ceramides and related lipid species in cellular extracts

A liquid chromatography-electrospray ionization tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous qualitative and quantitative determination of sphingolipid metabolites such as ceramides, sphingisine, sphinganine, sphingomyelins, and ceramide 1-phosphates in the extracts of human promyelocytic leukemia cells (HL-60). The assay uses C(4) ceramide as an internal standard; simple liquid extraction; a short XTerra MS C(18) (3 microm, 50 mm x2.0 mm) column; a gradient mobile phase of 5mM ammonium formate (pH 4.0)/methanol/tetrahydrofuran (5/2/3-->1/2/7); mass spectrometric detection using electrospray ionization. This LC-MS/MS method allowed the identification of 22 sphingolipid derivatives at pmol levels. In addition, this technique was successfully applied to analyze the changes of the sphingolipids profiles in cancer cells treated with apoptosis inducing agents, C(2) ceramide and H(2)O(2).     

Polyphenol amentoflavone affords neuroprotection against neonatal hypoxic-ischemic brain damage via multiple mechanisms

Flavonoids are naturally occurring polyphenolic compounds that have many biological properties, including antioxidative, anti-inflammatory and neuroprotective effects. Here, we report that amentoflavone significantly reduced cell death induced by staurosporine, etoposide and sodium nitroprusside in neuroblastoma SH-SY5Y cells. In post-natal day 7 rats, hypoxic-ischemic (H-I) brain damage induced by unilateral carotid ligation and hypoxia resulted in distinct features of neuronal cell death including apoptosis and necrosis. In this model, a systemic administration of amentoflavone (30 mg/kg) markedly reduced the H-I-induced brain tissue loss with a wide therapeutic time window up to 6 h after the onset of hypoxia. Amentoflavone blocked the activation of caspase 3, characteristic of apoptosis, and the proteolytic cleavage of its substrates following H-I injury. Amentoflavone also reduced the excitotoxic/necrotic cell death after H-I injury in vivo and after oxygen/glucose deprivation in mouse mixed cultures in vitro. Treatment of mouse microglial cells with amentoflavone resulted in a significant decrease in the lipopolysaccharide-induced production of nitric oxide and induction of inducible nitric oxide synthase and cyclo-oxygenase-2. Furthermore, amentoflavone decreased the inflammatory activation of microglia after H-I injury when assessed by the microglial-specific marker OX-42. These data demonstrate for the first time that amentoflavone strongly protects the neonatal brain from H-I injury by blocking multiple cellular events leading to brain damage.     

Involvement of p38 MAPK-mediated signaling in the calpeptin-mediated suppression of myogenic differentiation and fusion in C2C12 cells

Calpeptin inhibits myoblast fusion by inhibiting the activity of calpain. However, the mechanism by which calpeptin inhibits myogenesis is not completely understood. This study examined how calpeptin affects the expression of the myogenic regulatory factors (MRFs) and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) in differentiating C2C12 myoblasts. Consistent with previous reports, calpeptin inhibited the induction of μ-calpain and the formation of myotubes in these cells. In particular, calpeptin inhibited the expression of the early and mid differentiation markers including MyoD, Myf5, myogenin, and MRF4 as well as the expression of the late markers such as troponin T and myosin heavy chain (MyHC). Calpeptin also suppressed the phosphorylation of p38 MAPK in C2C12 cells. SB203580, a specific p38 inhibitor, prevented the expression of the muscle-specific markers and their fusion into myotubes in these cells, which was further accelerated in the presence of calpeptin. These findings suggest that calpeptin inhibits the myogenesis of skeletal muscle cells by down-regulating the MRFs and involving p38 MAPK signaling.     

A protein interaction network associated with asthma

Identifying candidate genes related to complex diseases or traits and mapping their relationships require a system-level analysis at a cellular scale. The objective of the present study is to systematically analyze the complex effects of interrelated genes and provide a framework for revealing their relationships in association with a specific disease (asthma in this case). We observed that protein-protein interaction (PPI) networks associated with asthma have a power-law connectivity distribution as many other biological networks have. The hub nodes and skeleton substructure of the result network are consistent with the prior knowledge about asthma pathways, and also suggest unknown candidate target genes associated with asthma, including GNB2L1, BRCA1, CBL, and VAV1. In particular, GNB2L1 appears to play a very important role in the asthma network through frequent interactions with key proteins in cellular signaling. This network-based approach represents an alternative method for analyzing the complex effects of candidate genes associated with complex diseases and suggesting a list of gene drug targets. The full list of genes and the analysis details are available in the following online supplementary materials: http://biosoft.kaist.ac.kr:8080/resources/asthma_ppi.     

Theiler's virus-induced intrinsic apoptosis in M1-D macrophages is Bax mediated and restricts virus infectivity: a mechanism for persistence of a cytolytic virus

Theiler's murine encephalomyelitis virus (TMEV), a member of the Cardiovirus genus in the family Picornaviridae, is a highly cytolytic virus that produces necrotic death in rodent cells except for macrophages, which undergo apoptosis. In the present study we have analyzed the kinetics of BeAn virus infection in M1-D cells, in order to temporally relate virus replication to the apoptotic signaling events. Apoptosis was associated with early exponential virus growth from 1 to 12 h postinfection (p.i.); however, >/=80% of peak infectivity was lost by 16 to 24 h p.i. The pan-caspase inhibitor qVD-OPh led to significantly higher virus yields, while zVAD-fmk completely inhibited virus replication until 10 h p.i., precluding its assessment in apoptosis. In contrast, while zVAD-fmk significantly inhibited BeAn virus replication in BHK-21 cells at 12 and 16 h p.i., virus replication at these time points was not altered by qVD-OPh. Bax translocation into mitochondria, efflux of cytochrome c into the cytoplasm, and activation of caspases 9 and 3 between approximately 8 and 12 h p.i. (all hallmarks of the intrinsic apoptotic pathway) were transiently inhibited by expression of Bcl-2, which is not expressed in M1-D cells. Thus, BeAn virus infection in M1-D macrophages, which restricts virus replication, provides a potential mechanism for modulating TMEV neurovirulence during persistence in the mouse central nervous system.