Dinucleotide repeat polymorphism in the human ceruloplasmin gene

We have identified a GT dinucleotide repeat polymorphism in intron 14 of the human ceruloplasmin gene. Observed heterozygosity for the polymorphism is 0.84.     

Developmental gene expression of gastrin receptor in rat stomach

Gastrin, which is present in fetal plasma, may have important roles in the development of gastric mucosa, since it is not only a potent stimulator of gastric acid secretion but also a growth promoting factor. Gastrin regulates various cellular functions via its receptors on cell membrane. Therefore, in order to elucidate a role for gastrin in the development of gastrointestinal system during gestation, Northern blot analysis was performed. The results of the study suggested that gastrin receptor is mainly present on parietal cells. Furthermore, proton pump and gastrin receptor gene expressions in parietal cells were strongly stimulated by the administration of exogenous gastrin. In conclusion, gastrin may be involved in the developmental change of parietal cells through its receptors.     

三江源国家公园种子植物区系特征分析

该研究在2017年和2018年多次野外调查的基础上,结合相关资料对三江源国家公园内的种子植物进行统计并分析其植物区系的组成、性质及特点。结果表明:(1)三江源国家公园共有种子植物50科232属832种,以耐旱耐寒的多年生草本为主,木本植物较少,是三江源自然保护区种子植物的核心分布区。(2)该公园以长江源园区植物资源丰富度最高,澜沧江源园区和黄河源园区依次递减,其中,有244种种子植物在3个园区内均有分布。(3)在科的层次上,小科和中等科是构成该园区科的主体,而以禾本科为代表的12个大科和较大科共同构成了该园区种子植物的优势科。在属的层次上,单种属是构成该园区属的主体,中等属所含种子植物种数最多。(4)该区科的分布区类型以世界分布类型为主,除世界分布科外,该园区的科主要体现了温带性质的分布特点。(5)该区属的分布区类型具有明显的温带性质,与欧亚大陆联系紧密,以北温带分布类型为主要组成成分。(6)该区种子植物的种可分为中国特有种和非中国特有种两大类,中国特有种的分布与横断山脉密切联系,影响该区区系的形成。非中国特有种的分布中亚成分和东亚成分为主,北温带成分、温带亚洲成分等的共同参与和影响下形成明显的温带性质。(7)该园区种子植物资源的丰富性、生活型的多样性及科、属、种的温带性质的分布特点,充分体现了园区的种子植物区系与其独特的地理位置和气候条件相适应。     

Alteration of familial ALS-linked mutant SOD1 solubility with disease progression: its modulation by the proteasome and Hsp70

Accumulation of misfolded Cu/Zn superoxide dismutase (SOD1) occurs in patients with a subgroup of familial amyotrophic lateral sclerosis (fALS). To identify the conversion of SOD1 from a normally soluble form to insoluble aggregates, we investigated the change of SOD1 solubility with aging in fALS-linked H46R SOD1 transgenic mice. Mutant SOD1 specifically altered to insoluble forms, which were sequentially separated into Triton X-100-insoluble/sodium dodecyl sulfate (SDS)-soluble and SDS-insoluble/formic acid-soluble species. In spinal cords, the levels of SDS-dissociable soluble SOD1 monomers and SDS-stable soluble dimers were significantly elevated before motor dysfunction onset. In COS-7 cells expressing H46R SOD1, treatment with proteasome inhibitors recapitulated the alteration of SOD1 solubility in transgenic mice. In contrast, overexpression of Hsp70 reduced accumulation of mutant-specific insoluble SOD1. SDS-soluble low molecular weight species of H46R SOD1 may appear as early misfolded intermediates when their concentration exceeds the capacity of the proteasome and molecular chaperones.     

Increased effect of fucoidan on lipoprotein lipase secretion in adipocytes

AimsFucoidan, a sulfated polysaccharide extracted from brown seaweed (F. vesiculosus) is recognized as an effective anticoagulant but its anti-lipidemic potency has not been well defined. We investigated the effect of fucoidan on lipoprotein lipase (LPL) secretion by human adipocytes.Main methodsLPL mRNA and protein expressions were measured using semi-quantitative RT-PCR, ELISA and immunohistochemistry in cultured adipocytes with or without fucoidan treatment. LPL enzyme activity was determined by a fluorometric assay.Key findingsIn cultured adipocytes, fucoidan induced LPL secretion in a dose- and time-dependent manner. An initial increase in LPL was maintained at a significant level but much slower than that in heparin-treated cells. Fucoidan also dose-dependently induced a cofactor of LPL, the apolipoprotein C-II (ApoC-II) secretion. In fucoidan-treated cells, LPL mRNA was time-dependently increased and LPL protein expression was also inceased. Treatment with both heparin and fucoidan showed no further increase in media LPL activity compared to heparin alone. In the conditioned medium from fucoidan-treated cells followed for 4 h, LPL activity decayed exponentially with half-life of about 180 min. In addition, the extracellular LPL mass in cycloheximide (a protein synthesis inhibitor) and fucoidan-treated cells did not change markedly, but LPL shifted significantly from active to inactive form.SignificanceThese results suggest that fucoidan acts like heparin by releasing LPL in addition to increasing the intracellular transport and decreasing the degradation of LPL in the medium. Furthermore, LPL and ApoC-II secretion induced by fucoidan may be involved in regulating plasma triglyceride lowering clearance.     

Segmental copy-number gain within the region of isopentenyl diphosphate isomerase genes in sporadic amyotrophic lateral sclerosis

Aims: Sporadic amyotrophic lateral sclerosis (SALS) seems to be a multifactorial disease, the pathogenesis of which may involve both genetic and environmental factors. The present study aims at identifying a possible genetic change that confers risk for SALS. Methods: We performed whole-genome screening of a copy-number variation (CNV) using a CNV beadchip, followed by real-time quantitative polymerase chain reaction (qPCR) and region-targeted high-density oligonucleotide tiling microarray. Results: Within the 40-kb region on 10p15.3 subtelomere, which harbours two genes encoding isopentenyl diphosphate isomerase 1 (IDI1) and IDI2, we found a segmental copy-number gain in a large proportion of SALS patients. qPCR analysis demonstrated the copy-number gain in 46 out of 83 SALS patients, as compared with 10 out of 99 controls (p = 4.86 × 10⁻¹¹, Odds Ratio 10.8); subsequent tiling microarray validated qPCR results and elucidated the fine structure of segmental gains. Conclusions: A segmental copy-number gain in the IDI1/IDI2 gene region may play a significant role in the pathogenesis of SALS.     

Prostaglandin E2-EP4 signaling initiates skin immune responses by promoting migration and maturation of Langerhans cells

Antigen-specific immune responses in the skin are initiated by antigen uptake into Langerhans cells and the subsequent migration of these cells to draining lymph nodes. Although prostaglandin E2 (PGE2) is produced substantially in skin exposed to antigen, its role remains unclear. Here we show that although Langerhans cells express all four PGE receptor subtypes, their migration to regional lymph nodes was decreased only in EP4-deficient (Ptger4-/-) mice and in wild-type mice treated with an EP4 antagonist. An EP4 agonist promoted the migration of Langerhans cells, increased their expression of costimulatory molecules and enhanced their ability to stimulate T cells in the mixed lymphocyte reaction in vitro. Contact hypersensitivity to antigen was impaired in Ptger4-/- mice and in wild-type mice treated with the EP4 antagonist during sensitization. PGE2-EP4 signaling thus facilitates initiation of skin immune responses by promoting the migration and maturation of Langerhans cells.