The plasticity of bone marrow cells (BMCs) remains controversial. The present study found that persistent injury induces efficient trans-differentiation of BMCs into functional hepatocytes. Mice with liver cirrhosis induced by carbon tetrachloride were injected with 1 x 10(5) non-treated green fluorescent protein (GFP)-positive BMCs via the tail vein. In these mice, transplanted GFP-positive BMCs efficiently migrated into the peri-portal area of liver lobules after one day, repopulating 25% of the recipient liver by 4 weeks. In contrast, no GFP-positive BMCs were detected following transplantation into control mice with undamaged livers. BMCs trans-differentiated into functional mature hepatocytes via immature hepatoblasts. Serum albumin levels were significantly elevated to compensate for chronic liver failure in BMC transplantation. These results reveal that recipient conditions and microenvironments represent key factors for successful cell therapy using BMCs.

Homologous dicarboxylic acids (C 2 -C 12 ), ketocarboxylic acids (ωC 2 -ωC 9 , pyruvic acid) and dicarbonyls (glyoxal and methylglyoxal) have been studied in the urban aerosol samples (PM 2.5 ) collected from the Hong Kong roadside atmosphere during winter and summer of 2003 using a capillary GC and GC-MS method. The concentrations of total dicarboxylic acids, ketocarboxylic acids, and α-dicarbonyls were higher in winter than in summer (except for some species like phthalic acid, Ph).Oxalic (C 2 ) acid was found as the most abundant species in summer, followed by Ph.Oxalic (C 2 ) acid was also found as the most abundant species in winter, but followed by malonic (C 3 ) acid. The C 2 diacid comprised 28-66 % of the total diacid concentrations. The diacids with higher carbon numbers were less abundant, although C 9 diacid was relatively abundant (2 %). Glyoxylic acid (ωC 2 ) and methylglyoxal were found as the most abundant ketocarboxylic acid and dicarbonyl in both seasons, * Corresponding author. Tel.: +86-852-27666011; fax: +86-852-23346389. E-mail address: ceslee@polyu.edu.hk (S.C. Lee).2 respectively. The concentrations of the total diacids, total ketoacids and total dicarbonyls ranged from 224 to 1381 ng m -3 , 10 to 89 ng m -3 and 5 to 21 ng m -3 , respectively. Their relative abundances in PM 2.5 mass were 1.18 %, 0.06 % and 0.02 %, respectively. High concentrations of toluene (winter: 33.8 µg m -3 ; summer: 41.3 µg m -3 ) and naphthalenes (winter: 1.2 µg m -3 ; summer: 1.9 µg m -3 ) observed were one possible source for the abundant phthalic and also methylmaleic acids detected.

Atmospheric particles were collected for one year (2001)(2002) at a site Gosan on Jeju Island, South Korea. The samples were analyzed for water-soluble dicarboxylic acids and related compounds using a capillary GC and GC/MS. Total carbon and nitrogen contents, as well as their stable isotopic ratios, were also determined using elemental analyzer (EA) and EA/IR/MS, respectively. Elemental and isotopic analyses were also performed after the HCl vapor treatment of aerosol samples. The results demonstrate that calcium carbonate of dust origin was not a significant component, except for a few dust event samples. Carbonates most likely reacted with acidic species (such as H 2 SO 4 , HNO 3 and organic acids) in the atmosphere during a long-range transport, and did not contribute to the total aerosol carbon, except for few strong dust episodes that occurred in spring. This study also demonstrates that nitrate and ammonium largely contribute to aerosol nitrogen and organic nitrogen is minor component in the Asian aerosols. Acidic aerosols enriched with sulfate likely adsorb NH 3 gas that is emitted from soils in Asia whereas mineral dust particles containing carbonate may adsorb HNO 3 and volatile organic acids.Homologous series of dicarboxylic acids (C 2 -C 12 ) including unsaturated structures as well as ketocarboxylic acids (C 2 -C 9 ) were detected in the aerosol samples with oxalic (C 2 ) acid being the most abundant species followed by malonic (C 3 ) or succinic (C 4 ) acids. Total concentrations of diacids (130-2070 ng m -3 ) are one or two orders of magnitude greater than those reported for remote marine aerosols in the North Pacific, but are equivalent to those reported for urban aerosols. Very high concentrations of dusts (up to 880 µg m -3 ) and watersoluble dicarboxylic acids were often observed in early spring. However, their correlation (r=0.27) is not strong throughout the campaign. Although both mineral dusts and diacids are derived from the Asian continent, they originate from different sources and source regions.Diacids are probably emitted from urban sources in East Asia and produced by secondary photochemical oxidation of their precursors, whereas dusts are derived from the arid interior regions. This study provides evidence for photochemical production of water-soluble organic acids in East Asia and the western North Pacific rim.3

Stress‐activated protein kinase/c‐Jun N‐terminal kinase (SAPK/JNK) responds to a variety of stress stimuli and controls cell fates such as cell cycle entrance, apoptosis and senescence. Stimuli such as ultraviolet irradiation and chemical reagents that damage genomic DNA induce the activation of the SAPK/JNK signaling pathway. However, it is unclear how the signal arising in the nucleus owing to DNA damage is transmitted to SAPK/JNK in the cytoplasm. Here, we report that the nuclear components Daxx and Ras‐association domain family 1C (RASSF1C) link DNA damage to SAPK/JNK activation in HeLa cells. In response to DNA damage, Daxx localized in promyelocytic leukaemia‐nuclear bodies (PML‐NBs) undergoes ubiquitination and degradation. RASSF1C, a tumor suppressor and newly identified binding partner of Daxx, is constitutively anchored by Daxx in PML‐NBs but is released from the nucleus when Daxx is degraded. This released RASSF1C translocates to cytoplasmic microtubules and participates in the activation of SAPK/JNK. Our data define a novel mechanism by which the Daxx–RASSF1C complex in PML‐NBs couples nuclear DNA damage to the cytoplasmic SAPK/JNK signaling pathway.

Ultraviolet (UV) irradiation stimulates stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/ JNK), which is a member of the mitogen-activated protein kinase (MAPK) superfamily and implicated in stress-induced apoptosis. UV also induces the activation of another MAPK member, extracellular signal-regulated kinase (ERK), which is typically involved in a growth-signaling cascade. However, the UV-induced signaling pathway leading to ERK activation, together with the physiological role, has remained unknown. Here we examined the molecular mechanism and physiological function of UV-induced ERK activation in human epidermoid carcinoma A431 cells that retain a high number of epidermal growth factor (EGF) receptors. UV-induced ERK activation was accompanied with the Tyr phosphorylation of EGF receptors, and both responses were completely abolished in the presence of a selective EGF receptor inhibitor (AG1478) or the Src inhibitor PP2 and by the expression of a kinase-dead Src mutant. On the other hand, SAPK/JNK activation by UV was partially inhibited by these inhibitors. UV stimulated Src activity in a manner similar to the ERK activation, but the Src activation was insensitive to AG1478. UV-induced cell apoptosis measured by DNA fragmentation and caspase 3 activation was enhanced by AG1478 and an ERK kinase inhibitor (U0126) but inhibited by EGF receptor stimulation by the agonist. These results indicate that UV-induced ERK activation, which provides a survival signal against stress-induced apoptosis, is mediated through Src-dependent Tyr phosphorylation of EGF receptors.