Leveraging Environment and Climate Change Initiatives for Corporate Excellence

This paper reviews selected initiatives taken by Asian countries to comply with emerging global sustainability standards, reporting, and management systems, and tracks the response of Asian businesses to global environmental concerns, examines market based innovations including new regulations that augmented corporate excellence, and identifies future directions for business that lead low carbon society. It recommends governments and business to join forces in supporting low carbon initiatives, drawing upon market mechanisms through reconfiguring national environmental policies and strategies.climate change initiatives; global sustainability standards; low carbon initiatives; environmental policies

mel-18,a Polycomb Group Gene, is Haploinsufficient for Murine Spontaneous Adenocarcinoma

ポリコーム遺伝子群は, ショウジョウバエでホメオボックス遺伝子群の負の制御因子として同定された。その遺伝子産物は核内でタンパク質複合体を形成し, 標的遺伝子の転写が抑制されるヘテロクロマチンの維持(クロマチンサイレンシング)に寄与している。哺乳類ホモログのmel-18のノックアウトマウスは, 体の前後軸形成異常, リンパ球の細胞周期異常による重篤な免疫不全を呈した。mel-18は細胞死も制御しており, 細胞周期, 細胞死双方への関与より, 癌との関連が予想された。mel-18発現の低下したNIH3T3細胞は腫瘍形質を獲得し, in vitroでは癌抑制の活性が確認されたが, mel-18欠損マウスは生後3～4週間で死亡するため, 生体レベルでの証明は不可能であった。近年mel-18へテロ接合性マウスに乳癌を中心とする腺癌の発生が認められた。腫瘍の残存mel-18遺伝子座には, 変異, 欠失は認められなかった。Mel-18タンパク質は核内で他のポリコームタンパク質等と複合体を形成するが, mel-18^マウスの臓器ではこの複合体が消失していた。抗Mel-18抗体を用いた蛍光免疫染色では, 野生型細胞では核内に十数個の粗大な顆粒状の構造物がみられ, これがMel-18を含むポリコームタンパク質複合体の一部ではないかと考えられた。mel-18へテロ接合性マウスの腫瘍細胞ではこの破砕像が観察された。正常マウス乳腺細胞にmel-18アンチセンスを導入すると, 高率に腫瘍を形成し, 核内のMel-18タンパク質局在は, mel-18^マウスの腫瘍細胞と同様の破砕パターンを呈した。他の乳癌関連遺伝子の検索では, mel-18の発現量の少ない細胞で癌抑制遺伝子のbrca1の発現が減少, 癌遺伝子のtbx2の発現が増加しており, これらがmel-18の標的遺伝子であることが示唆された。以上より, mel-18のハプロインサフィシエンシーは, Mel-18複合体を不安定化し, 標的遺伝子のへテロクロマチン領域の破綻により腫瘍原生獲得に至ったものと考えられた。The Polycomb group (PcG) gene products form protein complexes in mammalian cell nuclei and maintain chromatin silencing of target genes. mel-18,a mammalian PcG homologue, is considered to regulate cell cycle progression, cell death, or senescence based on the findings obtained from its knockout mice. Mel-18 participates in Polycomb protein complexes and the immunohistochemical analyses have shown that Mel-18 is located in the nucleus as a speckled distribution. Recently, mel-18 hemizygous mice have shown to develop adenocarcinomas, most of which were classified as breast cancers. Although no gross rearrangements or nucleotide mutations in the remaining mel-18 allele despite of the expression of Mel-18 protein in mel-18 hemizygous mice, we found that, in mel-18 hemizygous mice, a pattern of protein complexes including Mel-18 was destructed, and that a distribution pattern of Mel-18 changed to a micro-speckled pattern. In addition, murine mammary gland cells expressing reduced level of Mel-18 by antisense introduction acquired tumorigenicity and also showed an altered distribution of Mel-18 in the nucleus similar to those observed in tumor cells of mel-18 hemizygous mice. Examinations of the expression of other breast cancer-associated genes demonstrated that brca1 expression was reduced, whereas tbx2 expression was induced both in the mel-18 hemizygous tumor cells and mel-18 antisense-introduced cells. These results strongly suggest that mel-18 is a novel murine tumor suppressor gene and its haploinsufficiency results in tumorigenesis, possibly due to disruption of the protein complex formation and failure in silencing of target genes

Understanding avian Plasmodium distribution: the role of vector and host

Malaria parasites have a complex life cycle involving sexual reproduction in the mosquito vector and asexual proliferation in the vertebrate host. Mosquito vectors are therefore the definitive host of the malaria parasite. The literature on avian malaria parasites remains biased towards bird-parasite associations, and avian malaria vectors are not well studied in this system. My dissertation fills a gap in the current body of avian malaria research by using molecular techniques to document 1) patterns in phylogeographic structure of avian Plasmodium across geographic regions; 2) absence of vector specificity in two common mosquito species in Ithaca, New York; and 3) evidence that local vectors amplify a local avian Plasmodium lineage. In my first chapter, I review our current understanding about the associations between avian malaria vectors and avian Plasmodium. I synthesize this with literature on human malaria-mosquito interactions and mosquito feeding preferences to argue that it is crucial to study vector ecology to understand host-parasite dynamics. Variation in mosquito ecology could help explain patterns observed in avian malaria parasite infection. In chapter 2, I document patterns of phylogeographic structure in Plasmodium parasites sampled across the range of a single bird species. I demonstrate that geographic patterns in parasite lineage distribution are not solely attributable to differences in the parasites found in different bird species. In chapter 3, I describe the avian Plasmodium lineages found in two abundant, local ornithophilic mosquito species and show that parasites sampled from mosquitoes are represented by many diverse cytochrome b haplotypes. The most common of these haplotypes are shared between mosquito species, and overlap only slightly with those previously isolated directly from numerous bird species. In chapter 4, I report results from a feeding experiment using laboratory-reared mosquitoes and wild-caught birds naturally infected with Plasmodium. I examine the variation within Cx. pipiens in its ability to be invaded by the parasite by conducting PCR on individual mosquitoes following incubation with sufficient time to allow the complete digestion of the blood meal and development of sporozoites in the salivary glands

Traditional Japanese Formula Kigikenchuto Accelerates Healing of Pressure-Loading Skin Ulcer in Rats

We evaluated the effect of kigikenchuto (KKT), a traditional Japanese formula, in a modified rat pressure-loading skin ulcer model. Rats were divided into three groups, KKT extract orally administered (250 or 500 mg/kg/day for 35 days) and control. KKT shortened the duration until healing. Immunohistochemically, KKT increased CD-31-positive vessels in early phase and increased α-smooth muscle actin-(α-SMA-) positive fibroblastic cells in early phase and decreased them in late phase of wound healing. By Western blotting, KKT showed the potential to decrease inflammatory cytokines (MCP-1, IL-1β, and TNF-α) in early phase, decrease vascular endothelial growth factor in early phase and increase it in late phase, and modulate the expression of extracellular protein matrix (α-SMA, TGF-β1, bFGF, collagen III, and collagen I). These results suggested the possibility that KKT accelerates pressure ulcer healing through decreases of inflammatory cytokines, increase of angiogenesis, and induction of extracellular matrix remodeling

Dioxins and Fatty Acids in Breast Milk of Primiparas in Yonago District, Tottori Prefecture, Japan

We analyzed the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in breast milk collected 1 week after childbirth from 8 primiparas in Yonago district, Tottori Prefecture, and investigated the relationship between PCDDs or PCDFs and fatty acids in concentration, and the relationship between dioxin concentration and kind of daily foods. The mean total content of dioxins (PCDDs and PCDFs) was 0.48 pg-toxic equivalent (TEQ)/g (range 0.12?1.04 pg-TEQ/g) in breast milk, and 16.7 pg-TEQ/g-fat (range 9.6?32.7 pg-TEQ/g-fat) in total lipids of breast milk. The 8 primiparas showed a low mean dioxin concentration: the levels were lower in 6 of them and higher in 2 of them than in primiparas living in other cities in Japan. For 1 of the 2 mothers, the reason for the high level was thought to be her poor intake of vegetables in the diet. The total dioxin content was well correlated with the total lipid content ranging from 1% to 3%. Fatty acids with C16:0 and C18:1 dominated those with C12:0, C14:0, C16:1, C18: 2 and C18:0, which were commonly detected. The amount of fatty acids with C10:0, C20:1, C20:2, C20:3, C20:4, C22:5 and C22:6 was small. Gas chromatograms of these fatty acids generally showed similar distributions in breast milk of the 8 primiparas. The contents of fatty acids ranged from 17.1 to 31.3 mg/g (average 24.0 mg/g) in bulk breast milk. No clear correlation was found in concentration between PCDDs or PCDFs and specific fatty acids in breast milk

Reverse pharmacological effect of loop diuretics and altered rBSC1 expression in rats with lithium nephropathy

Reverse pharmacological effect of loop diuretics and altered rBSC1 expression in rats with lithium nephropathy.BackgroundRenal urinary concentration is associated with enhanced expression of rBSC1, a rat sodium cotransporter, in the thick ascending limb of Henle. Increased expression of rBSC1 was reported recently in nephrogenic diabetes insipidus induced by lithium chloride (Li nephropathy). However, the pathophysiological implication of altered rBSC1 expression has not yet been investigated.MethodsLi nephropathy was induced in rats by an oral administration of 40 mmol lithium/kg dry food. In rats with reduced urinary osmolality to less than 300 mOsm/kg H2O, we examined the expression of rBSC1 mRNA and protein, plasma arginine vasopressin (AVP) and RNA expression of kidney-specific water channel, aquaporin-2 (AQP2), of collecting ducts. Rats with Li nephropathy were treated with furosemide (3 mg/kg body weight), which blocks the activity of rBSC1, and changes in urine concentration, plasma AVP, medullary accumulation of Li ions, and apical AQP2 expression were determined.ResultsRats with Li nephropathy showed increased rBSC1 RNA and protein expression and reduced AQP2 RNA. In these rats, furosemide, which induces dilution of urine and polyuria in normal rats, resulted in a progressive and significant rise in urine osmolality from 167 ± 11 (mean ± SD) at baseline to 450 ± 45 mOsm/kg H2O at three hours after administration, and significant oliguria. In the same rats, plasma AVP decreased significantly from 5.7 to 3.0 pg/mL. In addition, recovery of apical AQP2 expression was noted in a proportion of epithelial cells of the collecting ducts. Although Li+ in the renal medulla was slightly lower in rats with Li nephropathy treated with furosemide, statistical significance was not achieved.ConclusionsOur results suggest that dehydration or high plasma AVP results in an enhanced rBSC1 expression in Li nephropathy, and that rBSC1 expression is closely associated with the adverse effects of Li ions on collecting duct function

Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles

初期化を阻害する転写因子が分化を促進する. 京都大学プレスリリース. 2013-04-02.Transcription factors (TFs) are able to regulate differentiation-related processes, including dedifferentiation and direct conversion, through the regulation of cell type-specific transcriptional profiles. However, the functional interactions between the TFs regulating different transcriptional profiles are not well understood. Here, we show that the TFs capable of inducing cell type-specific transcriptional profiles prevent the dedifferentiation induced by TFs for pluripotency. Of the large number of TFs expressed in a neural-lineage cell line, we identified a subset of TFs that, when overexpressed, strongly interfered with the dedifferentiation triggered by the procedure to generate induced pluripotent stem cells. This interference occurred through a maintenance mechanism of the cell type-specific transcriptional profile. Strikingly, the maintenance activity of the interfering TF set was strong enough to induce the cell line-specific transcriptional profile when overexpressed in a heterologous cell type. In addition, the TFs that interfered with dedifferentiation in hepatic-lineage cells involved TFs with known induction activity for hepatic-lineage cells. Our results suggest that dedifferentiation suppresses a cell type-specific transcriptional profile, which is primarily maintained by a small subset of TFs capable of inducing direct conversion. We anticipate that this functional correlation might be applicable in various cell types and might facilitate the identification of TFs with induction activity in efforts to understand differentiation

Dynamic Interaction of TTDA with TFIIH Is Stabilized by Nucleotide Excision Repair in Living Cells

Transcription/repair factor IIH (TFIIH) is essential for RNA polymerase II transcription and nucleotide excision repair (NER). This multi-subunit complex consists of ten polypeptides, including the recently identified small 8-kDa trichothiodystrophy group A (TTDA)/ hTFB5 protein. Patients belonging to the rare neurodevelopmental repair syndrome TTD-A carry inactivating mutations in the TTDA/hTFB5 gene. One of these mutations completely inactivates the protein, whereas other TFIIH genes only tolerate point mutations that do not compromise the essential role in transcription. Nevertheless, the severe NER-deficiency in TTD-A suggests that the TTDA protein is critical for repair. Using a fluorescently tagged and biologically active version of TTDA, we have investigated the involvement of TTDA in repair and transcription in living cells. Under non-challenging conditions, TTDA is present in two distinct kinetic pools: one bound to TFIIH, and a free fraction that shuttles between the cytoplasm and nucleus. After induction of NER-specific DNA lesions, the equilibrium between these two pools dramatically shifts towards a more stable association of TTDA to TFIIH. Modulating transcriptional activity in cells did not induce a similar shift in this equilibrium. Surprisingly, DNA conformations that only provoke an abortive-type of NER reaction do not result into a more stable incorporation of TTDA into TFIIH. These findings identify TTDA as the first TFIIH subunit with a primarily NER-dedicated role in vivo and indicate that its interaction with TFIIH reflects productive NER