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  • Werner, Erik, et al. (författare)
  • Hairpins in the conformations of a confined polymer
  • 2018
  • Ingår i: Biomicrofluidics. - 1932-1058. ; 12:2
  • Tidskriftsartikel (refereegranskat)abstract
    • If a semiflexible polymer confined to a narrow channel bends around by 180°, the polymer is said to exhibit a hairpin. The equilibrium extension statistics of the confined polymer are well understood when hairpins are vanishingly rare or when they are plentiful. Here, we analyze the extension statistics in the intermediate situation via experiments with DNA coated by the protein RecA, which enhances the stiffness of the DNA molecule by approximately one order of magnitude. We find that the extension distribution is highly non-Gaussian, in good agreement with Monte-Carlo simulations of confined discrete wormlike chains. We develop a simple model that qualitatively explains the form of the extension distribution. The model shows that the tail of the distribution at short extensions is determined by conformations with one hairpin. © 2018 Author(s).
  • Werner, Erik, et al. (författare)
  • Monomer distributions and intrachain collisions of a polymer confined to a channel
  • 2013
  • Ingår i: Macromolecules. - : The American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 46:16, s. 6644-6650
  • Tidskriftsartikel (refereegranskat)abstract
    • We study the conformations of a self-avoiding polymer confined to a channel by computing the cross-sectional distributions of the positions of its monomers. By means of Monte Carlo simulations for a self-avoiding, freely jointed chain, we determine how the cross-sectional distribution for a given monomer depends on its location in the polymer and how strongly this distribution is affected by self-avoidance. To this end we analyze how the frequency of intrachain collisions between monomers depends on their spatial position in the channel and on their location within the polymer. We show that most collisions occur between closely neighboring monomers. As a consequence, the collision probability depends only weakly on the spatial position of the monomers. Our results explain why the effect of self-avoidance on the monomer distributions is weaker than predicted by mean-field theory. We discuss the relevance of our results for studies of DNA conformations in nanofluidic channels.
  • Werner, Erik, et al. (författare)
  • Orientational correlations in confined DNA
  • 2012
  • Ingår i: Physical Review E. - : American Physical Society. - 1539-3755 .- 2470-0045 .- 2470-0053. ; 86:4
  • Tidskriftsartikel (refereegranskat)abstract
    • We study how the orientational correlations of DNA confined to nanochannels depend on the channel diameter D by means of Monte Carlo simulations and a mean-field theory. This theory describes DNA conformations in the experimentally relevant regime where Flory-de Gennes theory does not apply. We show how local correlations determine the dependence of the end-to-end distance of the DNA molecule upon D. Tapered nanochannels provide the necessary resolution in D to study experimentally how the extension of confined DNA molecules depends upon D. Our experimental and theoretical results are in qualitative agreement.
  • Wernly, Bernhard, et al. (författare)
  • Sex-specific outcome disparities in very old patients admitted to intensive care medicine: a propensity matched analysis
  • 2020
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Female and male very elderly intensive patients (VIPs) might differ in characteristics and outcomes. We aimed to compare female versus male VIPs in a large, multinational collective of VIPs with regards to outcome and predictors of mortality. In total, 7555 patients were included in this analysis, 3973 (53%) male and 3582 (47%) female patients. The primary endpoint was 30-day-mortality. Baseline characteristics, data on management and geriatric scores including frailty assessed by Clinical Frailty Scale (CFS) were documented. Two propensity scores (for being male) were obtained for consecutive matching, score 1 for baseline characteristics and score 2 for baseline characteristics and ICU management. Male VIPs were younger (835 vs. 84 +/- 5; p<0.001), less often frail (CFS>4; 38% versus 49%; p<0.001) but evidenced higher SOFA (7<plus/minus>6 versus 6 +/- 6 points; p<0.001) scores. After propensity score matching, no differences in baseline characteristics could be observed. In the paired analysis, the mortality in male VIPs was higher (mean difference 3.34% 95%CI 0.92-5.76%; p=0.007) compared to females. In both multivariable logistic regression models correcting for propensity score 1 (aOR 1.15 95%CI 1.03-1.27; p=0.007) and propensity score 2 (aOR 1.15 95%CI 1.04-1.27; p=0.007) male sex was independently associated with higher odds for 30-day-mortality. Of note, male gender was not associated with ICU mortality (OR 1.08 95%CI 0.98-1.19; p=0.14). Outcomes of elderly intensive care patients evidenced independent sex differences. Male sex was associated with adverse 30-day-mortality but not ICU-mortality. Further research to identify potential sex-specific risk factors after ICU discharge is warranted.Trial registration: NCT03134807 and NCT03370692; Registered on May 1, 2017 https://clinicaltrials.gov/ct2/show/NCT03370692.
  • Xu, Ning, et al. (författare)
  • MicroRNA-125b down-regulates matrix metallopeptidase 13 and inhibits cutaneous squamous cell carcinoma cell proliferation, migration, and invasion.
  • 2012
  • Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 287:35, s. 29899-908
  • Tidskriftsartikel (refereegranskat)abstract
    • Cutaneous squamous cell carcinoma (cSCC) is the second most common human cancer. Although dysregulation of microRNAs (miRNAs) is known to be involved in a variety of cancers, the role of miRNAs in cSCC is unclear. In this study, we aimed to identify tumor suppressive and oncogenic miRNAs involved in the pathogenesis of cSCC. MiRNA expression profiles in healthy skins (n = 4) and cSCCs (n = 4) were analyzed using MicroRNA Low Density Array. MiR-125b expression was analyzed by quantitative real-time PCR and in situ hybridization in skin biopsies from 40 healthy donors, 13 actinic keratosis, and 74 cSCC patients. The effect of miR-125b was analyzed in wound closure, colony formation, migration, and invasion assays in two cSCC cell lines, UT-SCC-7 and A431. The genes regulated by miR-125b in cSCC were identified by microarray analysis and its direct target was validated by luciferase reporter assay. Comparing cSCC with healthy skin, we identified four up-regulated miRNAs (miR-31, miR-135b, miR-21, and miR-223) and 54 down-regulated miRNAs, including miR-125b, whose function was further examined. We found that miR-125b suppressed proliferation, colony formation, migratory, and invasive capacity of cSCC cells. Matrix metallopeptidase 13 (MMP13) was identified as a direct target suppressed by miR-125b, and there was an inverse relationship between the expression of miR-125b and MMP13 in cSCC. Knockdown of MMP13 expression phenocopied the effects of miR-125b overexpression. These findings provide a novel molecular mechanism by which MMP13 is up-regulated in cSCCs and indicate that miR-125b plays a tumor suppressive role in cSCC.
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