Density alteration in non-physiological cells

In the present study an important phenomenon of cells was discovered: the change of intracellular density in cell's response to drug and environmental factors. For convenience, this phenomenon is named as "density alteration in non-physiological cells" ( DANCE). DANCE was determined by discontinuous sucrose gradient centrifugation (DSGC), in which cells were separated into several bands. The number and position of the bands in DSGC varied with the change of cell culture conditions, drugs, and physical process, indicating that cell's response to these factors was associated with alteration of intracellular density. Our results showed that the bands of cells were molecularly different from each other, such as the expression of some mRNAs. For most cells tested, intracellular density usually decreased when the cells were in bad conditions, in presence of drugs, or undergoing pathological changes. However, unlike other tissue cells, brain cells showed increased intracellular density in 24 hrs after the animal death. In addition, DANCE was found to be related to drug resistance, with higher drug-resistance in cells of lower intracellular density. Further study found that DANCE also occurred in microorganisms including bacteria and fungus, suggesting that DANCE might be a sensitive and general response of cells to drugs and environmental change. The mechanisms for DANCE are not clear. Based on our study the following causes were hypothesized: change of metabolism mode, change of cell membrane function, and pathological change. DANCE could be important in medical and biological sciences. Study of DANCE might be helpful to the understanding of drug resistance, development of new drugs, separation of new subtypes from a cell population, forensic analysis, and importantly, discovery of new physiological or pathological properties of cells

catena-Poly[[(2,2′-bipyridine)­manganese(II)]-μ3-4,4′-sulfonyl­dibenzoato]

In the title compound, [Mn(C14H8O6S)(C10H8N2)]n, the MnII ion is coordinated by four O atoms from three 4,4′-sulfonyl­dibenzoate (sdba) ligands and two N atoms from one 2,2′-bipyridine (2,2′-bipy) ligand in a distorted octa­hedral geometry. The manganese atoms are alternately bridged either by two sdba ligands, with an Mn⋯Mn separation of 12.284 (1) Å, or by two carboxyl­ate groups from two sdba ligands, with an Mn⋯Mn separation of 4.064 (1) Å, thus producing polymeric chains propagated in [101]. Weak inter­molecular C—H⋯O hydrogen bonds and π–π inter­actions [centroid–centroid distance of 3.730 (3) Å between the aromatic rings of neighbouring polymeric chains] further stabilize the crystal packing

Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells

The sensitivity of non-small cell lung cancer (NSCLC) patients to EGFR tyrosine kinase inhibitors (TKIs) is strongly associated with activating EGFR mutations. Although not as sensitive as patients harboring these mutations, some patients with wild-type EGFR (wtEGFR) remain responsive to EGFR TKIs, suggesting that the existence of unexplored mechanisms renders most of wtEGFR-expressing cancer cells insensitive.Here, we show that acquired resistance of wtEGFR-expressing cancer cells to an EGFR TKI, gefitinib, is associated with elevated expression of breast cancer resistance protein (BCRP/ABCG2), which in turn leads to gefitinib efflux from cells. In addition, BCRP/ABCG2 expression correlates with poor response to gefitinib in both cancer cell lines and lung cancer patients with wtEGFR. Co-treatment with BCRP/ABCG2 inhibitors enhanced the anti-tumor activity of gefitinib.Thus, BCRP/ABCG2 expression may be a predictor for poor efficacy of gefitinib treatment, and targeting BCRP/ABCG2 may broaden the use of gefitinib in patients with wtEGFR

Association of Interleukin-10 A-592C Polymorphism in Taiwanese Children with Kawasaki Disease

Elevated serum levels of interleukin-10 (IL-10) have been reported in patients with Kawasaki disease (KD). IL-10 reduces the inflammatory actions of macrophages and T cells and it may play a significant role in the regulation of inflammatory vascular damage associated with systemic vasculitis. The aim of this study was to examine whether -592 IL-10 promoter polymorphism is a susceptibility or severity marker of KD in Chinese patients in Taiwan. The study included 105 KD patients and 100 normal controls. Genotype and allelic frequencies for the IL-10 gene polymorphism in both groups were compared. There were no significant between-group differences in the genotype distribution of IL-10 A-592C gene polymorphism (P=0.08). However, the frequency of the -592*A allele was significantly increased in the patients with KD compared with controls (71.9% vs. 61.0%, P=0.019). The odds ratio for developing KD in individuals with IL-10-592*A allele was 1.64 (95% confidence interval, 1.06-2.52) compared to individuals with the IL-10-592*C allele. No significant difference was observed in the genotype and allelic frequencies for the IL-10 A-592C polymorphism between patients with and without coronary artery lesions. The IL-10-592*A allele may be involved in the development of KD in Taiwanese children

Transposon Ac/Ds-induced chromosomal rearrangements at the rice OsRLG5 locus

Previous studies have shown that pairs of closely-linked Ac/Ds transposable elements can induce various chromosomal rearrangements in plant genomes. To study chromosomal rearrangements in rice, we isolated a line (OsRLG5-161) that contains two inversely-oriented Ds insertions in OsRLG5 (Oryza sativa Receptor like kinase Gene 5). Among approximately 300 plants regenerated from OsRLG5-161 heterozygous seeds, 107 contained rearrangements including deletions, duplications and inversions of various sizes. Most rearrangements were induced by previously identified alternative transposition mechanism. Furthermore, we also detected a new class of rearrangements that contain juxtaposed inversions and deletions on the same chromosome. We propose that these novel alleles were generated by a previously unreported type of alternative transposition reactions involving the 5′ and 3′ termini of two inversely-oriented Ds elements located on the same chromatid. Finally, 11% of rearrangements contained inversions resulting from homologous recombination between the two inverted Ds elements in OsRLG5-161. The high frequency inheritance and great variety of rearrangements obtained suggests that the rice regeneration system results in a burst of transposition activity and a relaxation of the controls which normally limit the transposition competence of individual Ds termini. Together, these results demonstrate a greatly enlarged potential of the Ac/Ds system for plant chromosome engineering

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN