Mechanisms Preserving Insulin Action during High Dietary Fat Intake

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Urinary nucleic acid oxidation product levels show differential associations with pharmacological treatment in patients with type 2 diabetes

The relationship between RNA and DNA oxidation and pharmacological treatment has not been systematically investigated in patients with type 2 diabetes (T2D). We aimed to investigate the association between pharmacological treatments and levels of urinary markers of nucleic acid oxidation in T2D patients. Vejle Diabetes Biobank cohort data was nested into nationwide registry data. Multiple logistic regression was used to associate drug usage with risk of high (above median) RNA and DNA oxidation. Data from 2664 T2D patients (64% male, age range: 25–75) were included. Questionnaire-validated lipid lowering drug use was associated with low RNA oxidation (Odds ratio, OR 0.71, 95% CI: [0.59–0.87]). Insulin and non-specific antidiabetic drugs were associated with low DNA oxidation (insulin: OR 0.60, 95% CI [0.49–0.73]). Oral antidiabetics were associated with high DNA oxidation and RNA oxidation (OR 1.30, 95% CI [1.10–1.53] and OR 1.26, 95% CI [1.07–1.29]). Our findings indicate that diabetes-related drugs are associated with RNA and DNA oxidation and further studies are required to determine causality in T2D patients.     

Variable numbers of rRNA gene operons in Bacillus cereus strains

Abstract Ribosornal RNA operon organisation was analysed in two Bacillus cereus strains of different chromosome size, ATCC 10987 (5.4 Mb) and F0837/76 (2.4 Mb). We estimated that there were twelve and nine copies of the rRNA operons in these two strains, respectively. In B. cereus ATCC 10987 six rRNA operons were less than 10 kb apart, while in B. cereus F0837/76 four rRNA operons were similarly clustered. The origin of replication was located in the vicinity of a rRNA operon in both strains.     

Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versus-host disease

Skin is the most commonly affected organ in graft-versus-host disease (GVHD). To explore the role of Langerhans cells in GVHD, the principal dendritic cells of the skin, we studied the fate of these cells in mice transplanted with allogeneic bone marrow. In contrast to other dendritic cells, host Langerhans cells were replaced by donor Langerhans cells only when donor T cells were administered along with bone marrow, and the extent of Langerhans cell chimerism correlated with the dose of donor T cells injected. Donor T cells depleted host Langerhans cells through a Fas-dependent pathway and induced the production in skin of CCL20, which was required for the recruitment of donor Langerhans cells. Administration of donor T cells to bone marrow-chimeric mice with persistent host Langerhans cells, but not to mice whose Langerhans cells had been replaced, resulted in marked skin GVHD. These findings indicate a crucial role for donor T cells in host Langerhans cell replacement, and show that host dendritic cells can persist in nonlymphoid tissue for the duration of an animal's life and can trigger GVHD despite complete blood chimerism.     

Binding of FGF-1 variants to protein kinase CK2 correlates with mitogenicity

Fibroblast growth factor-1 (FGF-1) has both extra- and intracellular functions. To identify intracellular binding partners for FGF-1, we isolated proteins from U2OS human osteosarcoma cells interacting specifically with FGF-1. One of the isolated proteins was identified as protein kinase CK2 (CK2). We here provide evidence that FGF-1 binds to both the catalytic alpha-subunit and to the regulatory beta-subunit of CK2. The interaction between FGF-1 and CK2 alpha and beta was characterized by surface plasmon resonance, giving K(D) values of 0.4 +/- 0.3 and 1.2 +/- 0.2 microM, respectively. By using a novel assay for intracellular protein interaction, FGF-1 and CK2 alpha are shown to interact in vivo. In vitro, FGF-1 and FGF-2 are phosphorylated by CK2, and the presence of FGF-1 or FGF-2 was found to enhance the autophosphorylation of CK2 beta. A correlation between the mitogenic potential of FGF-1 mutants and their ability to bind to CK2 alpha was observed. The possible involvement of CK2 in the FGF-induced stimulation of DNA synthesis is discussed.     

A global non-conjugative Tet C plasmid,pRAS3, from Aeromonas salmonicida

Two 11.8 kb non-conjugative, but mobilizable R plasmids designated pRAS3.1 and pRAS3.2 were isolated from Aeromonas salmonicida subspecies salmonicida and atypical A. salmonicida, respectively. Differences between the plasmids were of minor extent and they are considered as being variants of the same plasmid, pRAS3. The genes repA, repB, mobA, mobC, mobD, and mobE were organized similar to corresponding genes in the small, mobilizable plasmid pTF-FC2 isolated from Acidithiobacillus ferrooxidans (previously Thiobacillus ferrooxidans). The nucleotide identity between these genes from pRAS3.1 and pTF-FC2 ranged from 89.5 to 98.2%. The tetA(C), tetR(C), and approximately 960 base pairs adjacent to tetR(C) were highly similar to the nucleotide sequence in pSC101. Plasmid pRAS3 was also found in a Scottish A. salmonicida strain, and appears to be identical to the R plasmid pJA8102-2 isolated from A. salmonicida in Japan.     

The Danish Registry for Plastic Surgery of the Breast: establishment of a nationwide registry for prospective follow-up,quality assessment,and investigation of breast surgery

Although numerous epidemiologic studies have examined the long-term safety of silicone breast implants during the past decade, there is a relative lack of surveillance data on short-term health effects and complications following cosmetic surgery of the breast. The Danish Registry for Plastic Surgery of the Breast, established in May of 1999, provides plastic surgeons with a nationwide system for the collection of preoperative, perioperative, and postoperative data on women undergoing breast implantation, breast reduction, or mastopexy. The purpose of the Registry is to examine short-term and, eventually, long-term local complications and possible health effects, and to contribute to an ongoing evaluation of surgical results and surveillance of the products. Furthermore, the Registry will allow the identification of new areas for research into cosmetic and reconstructive breast surgery. Women accepting registration in the Danish Registry for Plastic Surgery of the Breast complete a self-administered questionnaire focusing on medical history and demographic and behavioral factors. Preoperative blood samples are drawn for storage. Surgical data, postoperative results, and complications are registered following surgery and at postoperative visits. Currently, registration has been initiated at 24 private and public clinics, representing more than 80 percent of the plastic surgery clinics in Denmark. As of November of 2001, a total of 1472 women with breast implants and 560 women with breast reduction were included in the Registry. These figures are expected to increase annually by 1000 women undergoing breast implantation and 500 women undergoing breast reduction or mastopexy. The authors present their experience of establishing the first nationwide comprehensive clinical-epidemiologic database and biological bank for cosmetic and reconstructive surgery procedures.     

Seed 1-cysteine peroxiredoxin antioxidants are not involved in dormancy, but contribute to inhibition of germination during stress

Peroxiredoxins (Prx) are thiol-dependent antioxidants containing one (1-cysteine [-Cys]) or two (2-Cys) conserved Cys residues that protect lipids, enzymes, and DNA against reactive oxygen species. In plants, the 1-Cys Prxs are highly expressed during late seed development, and the expression pattern is dormancy related in mature seeds. We have expressed the Arabidopsis 1-Cys Prx AtPER1 in Escherichia coli and show that this protein has antioxidant activity in vitro and protects E. coli in vivo against the toxic oxidant cumene hydroperoxide. Although some 1-Cys Prxs are targeted to the nucleus, a green fluorescent protein-AtPER1 fusion protein was also localized to the cytoplasm in an onion epidermis subcellular localization assay. It has been proposed that seed Prxs are involved in maintenance of dormancy and/or protect the embryo and aleurone layer surviving desiccation against damage caused by reactive oxygen species. These hypotheses were tested using transgenic Arabidopsis lines overexpressing the barley (Hordeum vulgare) 1-Cys PER1 protein and lines with reduced levels of AtPER1 due to antisensing or RNA interference. We found no correlation between Prx levels and the duration of the after-ripening period required before germination. Thus, Prxs are unlikely to contribute to maintenance of dormancy. RNA interference lines almost devoid of AtPER1 protein developed and germinated normally under standard growth room conditions. However, seeds from lines overexpressing PER1 were less inclined to germinate than wild-type seeds in the presence of NaCl, mannitol, and methyl viologen, suggesting that Prx can sense harsh environmental surroundings and play a part in the inhibition of germination under unfavorable conditions.