Development of a hybrid scaffold and a bioreactor for cartilage regeneration

We developed a hybrid scaffold and a bioreactor for cartilage regeneration. The hybrid scaffold was developed as combination of two components： a biodegradable framework and hydrogel-containing chondrocytes. We performed the MTT cell proliferation assay to compare the proliferation and viability of chondrocytes on three types of scaffolds： an aiginate gel, the hybrid scaffold, and an alginate sponge. Cells were encapsulated in 2% agarose gel. The bioreactor consisted of a circulation system and a compression system. We performed dynamic cell culture on these agarose gels in the bioreactor for 3 days.     

Protein O-GlcNAcylation regulates Drosophila growth through the insulin signaling pathway

Modification of nuclear and cytosolic proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) is ubiquitous in cells. The in vivo function of the protein O-GlcNAcylation, however, is not well understood. Here, we manipulated the cellular O-GlcNAcylation level in Drosophila and found that it promotes developmental growth by enhancing insulin signaling. This increase in growth is due mainly to cell growth and not to cell proliferation. Our data suggest that the increase in the insulin signaling activity is mediated, at least in part, through O-GlcNAcylation of Akt. These results indicate that O-GlcNAcylation is one of the crucial mechanisms involved in control of insulin signaling during Drosophila development.     

Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus

We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest Pvalue (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.     

Curcumin: From ancient medicine to current clinical trials

Curcumin is the active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa). Curcumin has a surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. The pleiotropic activities of curcumin derive from its complex chemistry as well as its ability to influence multiple signaling pathways, including survival pathways such as those regulated by NF-kappaB, Akt, and growth factors; cytoprotective pathways dependent on Nrf2; and metastatic and angiogenic pathways. Curcumin is a free radical scavenger and hydrogen donor, and exhibits both pro- and antioxidant activity. It also binds metals, particularly iron and copper, and can function as an iron chelator. Curcumin is remarkably non-toxic and exhibits limited bioavailability. Curcumin exhibits great promise as a therapeutic agent, and is currently in human clinical trials for a variety of conditions, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis and Alzheimer's disease.     

Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis

We present a genome-wide association study of ileal Crohn disease and two independent replication studies that identify several new regions of association to Crohn disease. Specifically, in addition to the previously established CARD15 and IL23R associations, we identified strong and significantly replicated associations (combined P < 10(-10)) with an intergenic region on 10q21.1 and a coding variant in ATG16L1, the latter of which was also recently reported by another group. We also report strong associations with independent replication to variation in the genomic regions encoding PHOX2B, NCF4 and a predicted gene on 16q24.1 (FAM92B). Finally, we demonstrate that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium. Together, these findings suggest that autophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease.     

A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. We mapped FOP to chromosome 2q23-24 by linkage analysis and identified an identical heterozygous mutation (617G --> A; R206H) in the glycine-serine (GS) activation domain of ACVR1, a BMP type I receptor, in all affected individuals examined. Protein modeling predicts destabilization of the GS domain, consistent with constitutive activation of ACVR1 as the underlying cause of the ectopic chondrogenesis, osteogenesis and joint fusions seen in FOP.     

氯化物中黄钠铁矾除铁的热力学与动力学

对氯化物体系中锰结核浸出溶液采用黄钠铁矾净化除铁的热力学与动力学进行了研究．热力学分析表明，氯化物溶液中氯离子浓度升高能增大黄钠铁矾的溶解度，但在一般情况下（如ｃＣｌ－＜１０ｍｏｌ／Ｌ），完全可以将溶液中的铁以铁矾形式降到理想的程度；黄钠铁矾生成的最佳ｐＨ值范围为１．０～３．０；溶液中钠离子浓度升高有利于铁矾沉淀．动力学研究表明，氯化物中黄钠铁矾形成的表观活化能为９４．６６ｋＪ／ｍｏｌ，沉矾过程受化学反应控制．这些研究结果对锰结核浸出液中铁的分离以及氯化物体系中铁矾的沉淀具有指导作用．     

A new human HLA class II-related locus, DM

HLA class II molecules have a crucial role in the immune response to antigens. We have isolated two new class II-like complementary DNA sequences, RING6 and RING7, which map between the HLA-DNA and -DOB loci. They are novel members of the immunoglobulin gene family which may have diverged before the duplications that gave rise to the main class II loci. The RING6 and RING7 genes seem to encode alpha- and beta-chains of a previously undiscovered class II-related protein.     

A new species of the dentipes-subgroup of Triconia and a redescription of T. giesbrechti and T. elongata (Copepoda: Cyclopoida: Oncaeidae) from the tropical Pacific and the Korea Strait

A new species of Triconia in the family Oncaeidae, Triconia pacifica sp. nov., and a new form variant each of Triconia giesbrechti Böttger-Schnack and Triconia elongata Böttger-Schnack are described from two sites in the Pacific. Triconia pacifica can be distinguished from its sibling Triconia dentipes (Giesbrecht) by (1) morphometric characters, including the proportional lengths of distal endopod spines of swimming leg 4, and the relative length of the outer basal seta on P5, and by (2) a number of micro-structures on the appendages. The Pacific specimens of T. elongata and T. giesbrechti resemble the typical forms in morphometric characters, with some minor differences in proportional spine lengths on the swimming legs, and differ in a few micro-structures. The hitherto unknown male of T. giesbrechti is newly described. For all species/forms described, the intraspecific variability of proportional spine lengths on the endopods of P2–P4 is examined and discussed. http://www.zoobank.org/urn:lsid:zoobank.org:pub:6B41B0E2-0A5C-458B-8F9C-25000F208E24     

Suppressor of cytokine signaling 1 blocks mitosis in human melanoma cells

Hypermethylation of SOCS genes is associated with many human cancers, suggesting a role as tumor suppressors. As adaptor molecules for ubiquitin ligases, SOCS proteins modulate turnover of numerous target proteins. Few SOCS targets identified so far have a direct role in cell cycle progression; the mechanism by which SOCS regulate the cell cycle thus remains largely unknown. Here we show that SOCS1 overexpression inhibits in vitro and in vivo expansion of human melanoma cells, and that SOCS1 associates specifically with Cdh1, triggering its degradation by the proteasome. Cells therefore show a G1/S transition defect, as well as a secondary blockade in mitosis and accumulation of cells in metaphase. SOCS1 expression correlated with a reduction in cyclin D/E levels and an increase in the tumor suppressor p19, as well as the CDK inhibitor p53, explaining the G1/S transition defect. As a result of Cdh1 degradation, SOCS1-expressing cells accumulated cyclin B1 and securin, as well as apparently inactive Cdc20, in mitosis. Levels of the late mitotic Cdh1 substrate Aurora A did not change. These observations comprise a hitherto unreported mechanism of SOCS1 tumor suppression, suggesting this molecule as a candidate for the design of new therapeutic strategies for human melanoma.