The nuclear factor kappa B (NF-κB) pathway is pivotal in controlling survival and apoptosis of cancer cells. Macrophage migration inhibitory factor (MIF), a cytokine that regulates the immune response and tumorigenesis under inflammatory conditions, is upregulated in various tumors. However, the intracellular functions of MIF are unclear. In this study, we found that MIF directly interacted with thioredoxin-interacting protein (TXNIP), a tumor suppressor and known inhibitor of NF-κB activity, and MIF significantly induced NF-κB activation. MIF competed with TXNIP for NF-κB activation, and the intracellular MIF induced NF-κB target genes, including c-IAP2, Bcl-xL, ICAM-1, MMP2 and uPA, by inhibiting the interactions between TXNIP and HDACs or p65. Furthermore, we identified the interaction motifs between MIF and TXNIP via site-directed mutagenesis of their cysteine (Cys) residues. Cys and Cys of MIF and Cys and Cys of TXNIP were responsible for the interaction. MIF reversed the TXNIP-induced suppression of cell proliferation and migration. Overall, we suggest that MIF induces NF-κB activity by counter acting the inhibitory effect of TXNIP on the NF-κB pathway via direct interaction with TXNIP. These findings reveal a novel intracellular function of MIF in the progression of cancer.

Suppressor of cytokine signaling (SOCS) proteins are negative regulators of cytokine responses. Although recent reports have shown regulatory roles for SOCS proteins in innate and adaptive immunity, their roles in natural killer (NK) cell development are largely unknown. Here, we show that SOCS2 is involved in NK cell development. SOCS2−/− mice showed a high frequency of NK cells in the bone marrow and spleen. Knockdown of SOCS2 was associated with enhanced differentiation of NK cells in vitro, and the transplantation of hematopoietic stem cells (HSCs) into congenic mice resulted in enhanced differentiation in SOCS2−/− HSCs. We found that SOCS2 could inhibit Janus kinase 2 (JAK2) activity and JAK2-STAT5 signaling pathways via direct interaction with JAK2. Furthermore, SOCS2−/− mice showed a reduction in lung metastases and an increase in survival following melanoma challenge. Overall, our findings suggest that SOCS2 negatively regulates the development of NK cells by inhibiting JAK2 activity via direct interaction.

Aging is associated with an inevitable and universal loss of cell homeostasis and restricts an organism's lifespan by an increased susceptibility to diseases and tissue degeneration. The glucose uptake associated with producing energy for cell survival is one of the major causes of ROS production under physiological conditions. However, the overall mechanisms by which glucose uptake results in cellular senescence remain mysterious. In this study, we found that TXNIP deficiency accelerated the senescent phenotypes of MEF cells under high glucose condition. TXNIP‐/‐ MEF cells showed greater induced glucose uptake and ROS levels than wild‐type cells, and N‐acetylcysteine (NAC) treatment rescued the cellular senescence of TXNIP‐/‐ MEF cells. Interestingly, TXNIP‐/‐ MEF cells showed continuous activation of AKT during long‐term subculture, and AKT signaling inhibition completely blocked the cellular senescence of TXNIP‐/‐ MEF cells. In addition, we found that TXNIP interacted with AKT via the PH domain of AKT, and their interaction was increased by high glucose or H2O2 treatment. The inhibition of AKT activity by TXNIP was confirmed using western blotting and an in vitro kinase assay. TXNIP deficiency in type 1 diabetes mice (Akita) efficiently decreased the blood glucose levels and finally increased mouse survival. However, in normal mice, TXNIP deficiency induced metabolic aging of mice and cellular senescence of kidney cells by inducing AKT activity and aging‐associated gene expression. Altogether, these results suggest that TXNIP regulates cellular senescence by inhibiting AKT pathways via a direct interaction under conditions of glucose‐derived metabolic stress.

A gram-negative, non-motile, non-spore-forming and rod-shaped bacterial strain, CH15-1(T), was isolated from a sediment sample taken from Daechung Reservoir, South Korea, during the late-blooming period of cyanobacteria. Strain CH15-1(T) grew optimally at pH 7.0 and 30 °C. A phylogenetic analysis based on 16S rRNA gene sequences confirmed that strain CH15-1(T) belongs to the genus Arenimonas with the similarity range from 92.6-97.4 % and is closely related to Arenimonas oryziterrae YC6267(T) (97.4 %), Arenimonas composti TR7-09(T) (95.4 %), Arenimonas metalli CF5-1(T) (94.7 %), Arenimonas malthae CC-JY-1(T) (94.6 %) and Arenimonas donghaensis HO3-R19(T) (92.6 %). However, the DNA-DNA hybridization between strain CH15-1(T) and the closest strain, Arenimonas oryziterrae YC6267(T), was 8.9-12.9 %. The DNA G+C content was 63.9 mol% compared to A. oryziterrae YC626(T), 65.8 mol%. Strain CH15-1(T) included Q-8 as the major ubiquinone and phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and phosphatidylmonomethylethanolamine as the major polar lipids. The major fatty acids (>5 %) were iso-C(15 : 0), iso-C(16 : 0), iso-C(14 : 0), iso-C(11 : 0) 3-OH, iso-C(17 : 0) and summed feature 9 (iso-C(17 : 1)ω9c and/or C(16 : 0) 10-methyl). On the basis of phylogenetic, phenotypic and genetic data, strain CH15-1(T) was classified in the genus Arenimonas as a member of a novel species, for which the name Arenimonas daechungensis sp. nov. is proposed. The type strain is CH15-1(T) ( = KCTC 23553(T) = DSM 24763(T)).

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Strain CH15-11T , isolated from a sediment sample taken from Daechung Reservoir, SouthKorea, during the late-blooming period of cyanobacteria, was found to be a Gram-stain-negative, non-motile, non-spore-forming, rod-shaped and aerobic bacterium. Strain CH15-11 T grew optimally at pH 7 and 28-30 6C. According to a phylogenetic tree based on 16S rRNA gene sequences, strain CH15-11 T belonged to the genus Sphingomonas and clustered withSphingomonas sediminicola Dae 20 T , with which it shared the highest 16S rRNA gene sequence similarity (97.6 %). Chemotaxonomic analysis showed that strain CH15-11T had characteristics typical of members of the genus Sphingomonas, such as the presence of sphingoglycolipid, ubiquinone Q-10 and sym-homospermidine. Plus, strain CH15-11 T included summed feature 8 (C 18 : 1 v7c and/or C 18 : 1 v6c) and C 16 : 0 as the major fatty acids. The genomic DNA G+C content was 65.6 mol%. Sequence data showed that strain CH15-11 T was most closely related to Sphingomonas sediminicola Dae 20 T (97.6 %), Sphingomonas ginsengisoli Gsoil 634 T (97.2 %) and Sphingomonas jaspi TDMA-16 T (97.0 %). However, the DNA-DNA relatedness values between strain CH15-11 T and the most closely related type strains were within a range of 35-59 %. Thus, based on the phylogenetic, phenotypic and genetic data, strain CH15-11 T wasclassified as a member of the genus Sphingomonas as a representative of a novel species, for which the name Sphingomonas daechungensis sp. nov. is proposed. The type strain is CH15-11 T (5KCTC 23718 T 5JCM 17887 T ).The genus Sphingomonas was first proposed by Yabuuchi et al. (1990) and the genus description has been subsequently emended by Takeuchi et al. (2001), Yabuuchi et al. (2002 and Busse et al. (2003). A taxonomic study classified the genus as part of the family Sphingomonadaceae of the class Alphaproteobacteria. Based on the 16S rRNA gene sequences, polyamine patterns and polar lipid profiles, Takeuchi et al. (2001) proposed that the genus Sphingomonas should be divided into four genera, Sphingomonas, Novosphingobium, Sphingobium and Sphingopyxis. At the time of writing, the genus Sphingomonas consists of more than 60 species with validly published names. Members of the genus Sphingomonas are aerobic, rodshaped, Gram-reaction-negative, yellow-to orange-or redpigmented colonies and display the presence of 2-hydroxy fatty acids (C 14 : 0 2-OH) and the absence of 3-hydroxy fatty acids. The species of the genus also contain ubiquinone Q-10, sphingoglycolipid and homospermidine as the major respiratory quinone, polar lipid and polyamine, respectively. The present study reports on the taxonomic characterization of a Sphingomonas-like bacterial strain, CH15-11 T , which was isolated from a shoreline area, Chusori, of Daechung Reservoir in the central region of South Korea during the late-blooming period of cyanobacteria in summer. The isolated strain was identified using the EzTaxon-e database (http://eztaxon-e.ezbiocloud.et/; Kim et al., 2012) on the basis of 16S rRNA gene sequence data....

A novel Gram-reaction-positive bacterium, strain CH22-21 T , was isolated from a water sample taken from Daechung Reservoir, Republic of Korea, during the late-blooming period of cyanobacteria. Cells of strain CH22-21 T were non-motile, ciliated short rods that formed creamywhite colonies on half-strength modified R2A agar. Chemotaxonomic results showed menaquinone MK-9(H 6 ) as the predominant respiratory menaquinone, diphosphatidylglycerol, phosphatidylinositol and phosphatidylinositolmannoside as major polar lipids, 16 : 1v5c, 16 : 0, 17 : 1v8c and 18 : 1v9c as major fatty acids, and a DNA G+C content of 71.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequencing indicated that the strain formed a separate lineage within the order Acidimicrobiales, showing similarity values of ,92.3 % with its closest phylogenetic neighbours. The combined genotypic and phenotypic data showed that strain CH22-21 T could be distinguished from all genera within the order Acidimicrobiales and represented a novel species of a new genus in the family Iamiaceae, for which the name Aquihabitans dachungensis gen. nov., sp. nov. is proposed. The type strain of Aquihabitans dachungensis is CH22-21 T (5KCTC 19849 T 5JCM 17787 T ).Cyanobacterial blooms are a frequent summer occurrence in Daechung Reservoir, central South Korea (Oh et al., 2007), and have a negative impact on water quality and water utilization. Serious blooms of cyanobacteria produce a distinctive taste and odour to the water, and create a health hazard. While studying the interaction between cyanobacteria and heterotrophic bacteria thriving among the cyanobacteria, a Gram-positive bacterium, strain CH22-21 T , forming a lineage in the order Acidimicrobiales was isolated. At the time of writing, the class Actinobacteria comprises five subclasses: Acidimicrobidae, Actinobacteridae, Coriobacteridae, Nitriliruptoridae and Rubrobacteridae. However, most of the genera and species are located in the subclass Actinobacteridae, with very few in the other four subclasses. In addition, there are two recognized families, Acidimicrobiaceae and Iamiaceae. In this study, the morphological, physiological, biochemical, chemotaxonomic and phylogenetic properties of strain CH22-21 T are examined to reveal its taxonomic position.A novel bacterium, strain CH22-21 T , with a high genomic DNA G+C content was isolated. Water samples were initially diluted serially in a 0.85 % saline solution, then aliquots of each serial dilution were spread on half-strength modified R2A agar (Difco) and incubated at room temperature (25 u C) for 1 month. One creamy-white colony, designated strain CH22-21 T , was isolated and subcultivated on half-strength modified R2A agar at 30 uC for 4 weeks. Based on phylogenetic, phenotypic and chemotaxonomic analyses, the isolate was found to represent a novel species in a new genus in the order Acidimicrobiales. For further classification, the isolate was subjected to a polyphasic investigation.The Gram reaction was determined using a Gram stain kit (Becton Dickin...