Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex

Peer reviewedPublisher PD

Agarose-stabilized gold nanoparticles for surface-enhanced Raman spectroscopic detection of DNA nucleosides

doi:10.1063/1.2192573 http://scitation.aip.org/getpdf/servlet/GetPDFServlet?filetype=pdf&id=APPLAB000088000015153114000001&idtype=cvips&prog=normal&doi=10.1063/1.2192573We present surface-enhanced Raman scattering (SERS) studies of DNA nucleosides using biologically benign agarose-stabilized gold nanoparticles (AAuNP). We compare the SERS activity of nucleosides with AAuNP to that of commercially obtained citrate-stabilized gold nanoparticles and find the SERS activity to be an order of magnitude higher with AAuNP. The higher SERS activity is explained in terms of the agarose matrix, which provides pathways for the gold nanoparticles to have distinct arrangements that result in stronger internal plasmon resonances.This work was supported through the University of Missouri Research Board grants URB04-023 (S.G.) and URB03-080 (M.C. and K.V.K.), NSF under Grant No. DMR-0413601and the NCI under Grant No. IR0ICA119412-01. The gold nanoparticles were produced and supplied by the University of Missouri Nanoparticle Production Core Facility

Free energy barrier for melittin reorientation from a membrane-bound state to a transmembrane state

An important step in a phospholipid membrane pore formation by melittin antimicrobial peptide is a reorientation of the peptide from a surface into a transmembrane conformation. In this work we perform umbrella sampling simulations to calculate the potential of mean force (PMF) for the reorientation of melittin from a surface-bound state to a transmembrane state and provide a molecular level insight into understanding peptide and lipid properties that influence the existence of the free energy barrier. The PMFs were calculated for a peptide to lipid (P/L) ratio of 1/128 and 4/128. We observe that the free energy barrier is reduced when the P/L ratio increased. In addition, we study the cooperative effect; specifically we investigate if the barrier is smaller for a second melittin reorientation, given that another neighboring melittin was already in the transmembrane state. We observe that indeed the barrier of the PMF curve is reduced in this case, thus confirming the presence of a cooperative effect

Replication Stress-Induced Chromosome Breakage Is Correlated with Replication Fork Progression and Is Preceded by Single-Stranded DNA Formation

Chromosome breakage as a result of replication stress has been hypothesized to be the direct consequence of defective replication fork progression, or “collapsed” replication forks. However, direct and genome-wide evidence that collapsed replication forks give rise to chromosome breakage is still lacking. Previously we showed that a yeast replication checkpoint mutant mec1-1, after transient exposure to replication impediment imposed by hydroxyurea (HU), failed to complete DNA replication, accumulated single-stranded DNA (ssDNA) at the replication forks, and fragmented its chromosomes. In this study, by following replication fork progression genome-wide via ssDNA detection and by direct mapping of chromosome breakage after HU exposure, we have tested the hypothesis that the chromosome breakage in mec1 cells occurs at collapsed replication forks. We demonstrate that sites of chromosome breakage indeed correlate with replication fork locations. Moreover, ssDNA can be detected prior to chromosome breakage, suggesting that ssDNA accumulation is the common precursor to double strand breaks at collapsed replication forks

The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation

Peer reviewedPublisher PD

The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time

Peer reviewedPreprin

Asymptotic Safety, Emergence and Minimal Length

There seems to be a common prejudice that asymptotic safety is either incompatible with, or at best unrelated to, the other topics in the title. This is not the case. In fact, we show that 1) the existence of a fixed point with suitable properties is a promising way of deriving emergent properties of gravity, and 2) there is a sense in which asymptotic safety implies a minimal length. In so doing we also discuss possible signatures of asymptotic safety in scattering experiments.Comment: LaTEX, 20 pages, 2 figures; v.2: minor changes, reflecting published versio

Prevention of tracheal cartilage injury with modified Griggs technique during percutaneous tracheostomy - Randomized controlled cadaver study

Introduction: Tracheal stenosis is the most common severe late complication of percutaneous tracheostomy causing significant decrease in quality of life. Applying modified Griggs technique reduced the number of late tracheal stenoses observed in our clinical study. The aim of this study was to investigate the mechanism of this relationship. Materials and methods: Forty-six cadavers were randomized into two groups according to the mode of intervention during 2006-2008. Traditional versus modified Griggs technique was applied in the two groups consequently. Wider incision, surgical preparation, and bidirectional forceps dilation of tracheal wall were applied in modified technique. Injured cartilages were inspected by sight and touch consequently. Age, gender, level of intervention, and number of injured tracheal cartilages were registered. Results: Significantly less frequent tracheal cartilage injury was observed after modified (9%) than original (91%) Griggs technique (p<0.001). A moderate association between cartilage injury and increasing age was observed, whereas the level of intervention (p=0.445) and to gender (p=0.35) was not related to injury. Risk of cartilage injury decreased significantly (OR: 0.0264, 95%, CI: 0.005-0.153) with modified Griggs technique as determined in adjusted logistic regression model. Discussion: Modified Griggs technique decreased the risk of tracheal cartilage injury significantly in our cadaver study. This observation may explain the decreased number of late tracheal stenosis after application of the modified Griggs method. © 2012 Akadémiai Kiadó, Budapes

Hepatitis C Virus (HCV)-Specific Immune Responses of Long‐Term Injection Drug Users Frequently Exposed to HCV

BACKGROUND: Injection drug users (IDUs) who successfully clear hepatitis C virus (HCV) have a reduced risk of developing chronic reinfection, despite their continuing exposure to the virus. To identify immunological correlates for this apparent protection, we studied HCV-specific immune responses in long-term IDUs (duration, >10 years). METHODS: HCV-specific T cell responses were assessed in proliferation, enzyme-linked immunospot (ELISPOT), interferon (IFN)–γ secretion, and cytotoxicity assays, whereas HCV-specific antibodies were assessed in enzyme immunoassays (EIAs), chemiluminescent assays, and in vitro neutralization assays. RESULTS: HCV-specific T cell proliferation and IFN-γ production were more common in nonviremic EIA-positive IDUs (16 [94%] of 17 IDUs) than in viremic EIA-positive IDUs (9 [45%] of 20 IDUs) (P = .003). They were also noted in 16 (62%) of 26 nonviremic EIA-negative IDUs. In contrast, 19 (90%) of 21 viremic IDUs displayed neutralizing antibodies (nAbs), compared with 9 (56%) of 16 nonviremic EIA-positive IDUs (P = .04) and 0 of 24 nonviremic EIA-negative IDUs. Nonviremic IDUs with nAbs were older (P = .0115) than those without nAbs, but these groups did not differ in terms of either injection drug use duration or HCV-specific T cell responses. CONCLUSION: The reduced risk of HCV persistence in IDUs previously recovered from HCV infection correlated with T cell responses, and prolonged antigenic stimulation appears to be required to maintain humoral responses