Muts Homolog Sliding Clamps Shield the DNA from Binding Proteins

Hanne, Jeungphill,Britton, Brooke M.,Park, Jonghyun,Liu, Jiaquan,Martin-Lopez, Juana,Jones, Nathan,Schoffner, Matthew,Klajner, Piotr,Bundschuh, Ralf,Lee, Jong-Bong,Fishel, Richard Published for the Biophysical Society by the Rocke 2019 Biophysical journal Vol.116 No.3

MutS homolog sliding clamps shield the DNA from binding proteins

Hanne, Jeungphill,Britton, Brooke M.,Park, Jonghyun,Liu, Jiaquan,Martí,n-Lí,ó,pez, Juana,Jones, Nathan,Schoffner, Matthew,Klajner, Piotr,Bundschuh, Ralf,Lee, Jong-Bong,Fishel, Richar American Society for Biochemistry and Molecular Bi 2018 The Journal of biological chemistry Vol.293 No.37

<P>Sliding clamps on DNA consist of evolutionarily conserved enzymes that coordinate DNA replication, repair, and the cellular DNA damage response. MutS homolog (MSH) proteins initiate mismatch repair (MMR) by recognizing mispaired nucleotides and in the presence of ATP form stable sliding clamps that randomly diffuse along the DNA. The MSH sliding clamps subsequently load MutL homolog (MLH/PMS) proteins that form a second extremely stable sliding clamp, which together coordinate downstream MMR components with the excision-initiation site that may be hundreds to thousands of nucleotides distant from the mismatch. Specific or nonspecific binding of other proteins to the DNA between the mismatch and the distant excision-initiation site could conceivably obstruct the free diffusion of these MMR sliding clamps, inhibiting their ability to initiate repair. Here, we employed bulk biochemical analysis, single-molecule fluorescence imaging, and mathematical modeling to determine how sliding clamps might overcome such hindrances along the DNA. Using both bacterial and human MSH proteins, we found that increasing the number of MSH sliding clamps on a DNA decreased the association of the Escherichia coli transcriptional repressor LacI to its cognate promoter LacO. Our results suggest a simple mechanism whereby thermal diffusion of MSH sliding clamps along the DNA alters the association kinetics of other DNA-binding proteins over extended distances. These observations appear generally applicable to any stable sliding clamp that forms on DNA.</P>

Poster Session : PS 0101 ; Cardiology : Intracardiac Bronchogenic Cyst: Report of a Growing Lesion

( Jong Hanne Park ),( Goo Yeong Cho ),( Kay Hyun Park ),( Il Young Oh ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Introduction: Intracardiac bronchogenic cyst is a rare congenital malformation which is a remnant from abnormal budding of the embryonic foregut. As most of the intracardiac cysts are surgically removed promptly after detection, the natural course of intracardiac bronchogenic cyst is unknown. Case Presentation: 35-year-old man on adjuvant chemotherapy for gastric cancer presented with rapidly growing intracardiac mass incidentally detected at follow-up CT scan. Retrospective review of his pre-op stomach CT scan and follow-up abdomen CT scan revealed that the cyst had increased up to 6-fold in volume over a period of 13 months. Transthoracic echocardiography and magnetic resonance imaging revealed a homogenous cystic mass located at the interatrial septum. The patient underwent surgical excision of the mass. Histopathology identified columnar epithelial cells with focal cilia, consistent with the diagnosis of bronchogenic cyst. At immediate post-operation, 12-lead ECG showed CAVB, which persisted 6 days after surgery. A dual-chamber pacemaker was then implanted before discharge. At two months follow up, the patient was symptom free without any evidence of cardiac tumor or gastric cancer recurrence. Discussion: Here, we report a case of incidentally detected intracardiac bronchogenic cyst which was rapidly growing. To our knowledge, this is the fi rst report documenting growth of an intracardiac bronchogenic cyst in adult. Generally, growth of bronchogenic cyst is thought to be result of mucus accumulation, bleeding, infection or malignant transformation. We speculate that chronic infl ammation precipitated by adjuvant chemotherapy could be the cause of cyst growth.

Cascading MutS and MutL sliding clamps control DNA diffusion to activate mismatch repair

Liu, Jiaquan,Hanne, Jeungphill,Britton, Brooke M.,Bennett, Jared,Kim, Daehyung,Lee, Jong-Bong,Fishel, Richard Nature Publishing Group, a division of Macmillan P 2016 Nature Vol.539 No.7630

<P>Mismatched nucleotides arise from polymerase misincorporation errors, recombination between heteroallelic parents and chemical or physical DNA damage(1). Highly conserved MutS (MSH) and MutL (MLH/PMS) homologues initiate mismatch repair and, in higher eukaryotes, act as DNA damage sensors that can trigger apoptosis(2). Defects in human mismatch repair genes cause Lynch syndrome or hereditary non-polyposis colorectal cancer and 10-40% of related sporadic tumours(3). However, the collaborative mechanics of MSH and MLH/PMS proteins have not been resolved in any organism. We visualized Escherichia coli (Ec) ensemble mismatch repair and confirmed that EcMutS mismatch recognition results in the formation of stable ATP-bound sliding clamps that randomly diffuse along the DNA with intermittent backbone contact. The EcMutS sliding clamps act as a platform to recruit EcMutL onto the mismatched DNA, forming an EcMutS-EcMutL search complex that then closely follows the DNA backbone. ATP binding by EcMutL establishes a second long-lived DNA clamp that oscillates between the principal EcMutS-EcMutL search complex and unrestricted EcMutS and EcMutL sliding clamps. The EcMutH endonuclease that targets mismatch repair excision only binds clamped EcMutL, increasing its DNA association kinetics by more than 1,000-fold. The assembly of an EcMutS-EcMutL-EcMutH search complex illustrates how sequential stable sliding clamps can modulate one-dimensional diffusion mechanics along the DNA to direct mismatch repair.</P>

The Third Version of the Copenhagen Psychosocial Questionnaire

Hermann Burr,Hanne Berthelsen,Salvador Moncada,Matthias Nübling,Emilie Dupret,Yucel Demiral,John Oudyk,Tage S. Kristensen,Clara Llorens,Albert Navarro,Hans-Joachim Lincke,Christine Bocéréan,Ceyda Saha 한국산업안전보건공단 산업안전보건연구원 2019 Safety and health at work Vol.10 No.4

Introduction: A new third version of the Copenhagen Psychosocial Questionnaire (COPSOQ III) has been developed in response to trends in working life, theoretical concepts, and international experience. A key component of the COPSOQ III is a defined set of mandatory core items to be included in national short, middle, and long versions of the questionnaire. The aim of the present article is to present and test the reliability of the new international middle version of the COPSOQ III. Methods: The questionnaire was tested among 23,361 employees during 2016e2017 in Canada, Spain, France, Germany, Sweden, and Turkey. A total of 26 dimensions (measured through scales or single items) of the middle version and two from the long version were tested. Psychometric properties of the dimensions were assessed regarding reliability (Cronbach a), ceiling and floor effects (fractions with extreme answers), and distinctiveness (correlations with other dimensions). Results: Most international middle dimensions had satisfactory reliability in most countries, though some ceiling and floor effects were present. Dimensions with missing values were rare. Most dimensions had low to medium intercorrelations. Conclusions: The COPSOQ III offers reliable and distinct measures of a wide range of psychosocial dimensions of modern working life in different countries; although a few measures could be improved. Future testing should focus on validation of the COPSOQ items and dimensions using both qualitative and quantitative approaches. Such investigations would enhance the basis for recommendations using the COPSOQ III.

Development of intestinal ischemia/reperfusion-induced acute kidney injury in rats with or without chronic kidney disease: Cytokine/ chemokine response and effect of α-melanocyte-stimulating hormone

( Martin Skott ),( Rikke Nørregaard ),( Hanne Birke Sørensen ),( Johan Palmfeldt ),( Tae Hwan Kwon ),( Thomas Jonassen ),( Jørgen Frøkiær ),( Søren Nielsen ) 대한신장학회 2014 Kidney Research and Clinical Practice Vol.33 No.2

Background: The primary aim of the study was to investigate the cytokine/chemokine response in the kidney, lung, and liver following acute kidney injury(AKI). The secondary aim was to test whether α-melanocyte-stimulating hormone(α-MSH) could prevent a reduction in organ function, and attenuate the inflammatorycytokine/chemokine response within the kidney, lung, and liver following AKIin rats with or without preexisting chronic kidney disease (CKD). Methods: A two-stage animal model, in which AKI was induced in rats withpreexisting CKD, induced by 5/6 nephrectomy (Nx), was used. Six weeks later, AKIwas induced by intestinal ischemia and reperfusion (IIR). Sham procedures [S(Nx)and S(IIR)] were also performed. Results: Increasing levels of serum creatinine (sCr) demonstrated progressive developmentof CKD in response to Nx, and following IIR sCr levels increased furthersignificantly, except in the S(Nx) group treated with α-MSH. However, no significantdifferences in the fractional increase in sCr were observed between any of the groupsexposed to IIR. In kidney, lung, and liver tissue the levels of interleukin (IL)-1β weresignificantly higher in rats undergoing IIR when compared to the S(IIR) and control rats. The same pattern was observed for the chemokine monocyte chemoattractant protein(MCP)-1 in lung and liver tissue. Furthermore, kidney IL-1β and RANTES levels weresignificantly increased after IIR in the Nx rats compared to the S(Nx) rats. Conclusion: Both the functional parameters and the cytokine/chemokine response areas dramatic when AKI is superimposed onto CKD as onto non-CKD. No convincingprotective effect of α-MSH was detected.

The Third Version of the Copenhagen Psychosocial Questionnaire

Burr, Hermann,Berthelsen, Hanne,Moncada, Salvador,Nubling, Matthias,Dupret, Emilie,Demiral, Yucel,Oudyk, John,Kristensen, Tage S.,Llorens, Clara,Navarro, Albert,Lincke, Hans-Joachim,Bocerean, Christin Occupational Safety and Health Research Institute 2019 Safety and health at work Vol.10 No.4

Introduction: A new third version of the Copenhagen Psychosocial Questionnaire (COPSOQ III) has been developed in response to trends in working life, theoretical concepts, and international experience. A key component of the COPSOQ III is a defined set of mandatory core items to be included in national short, middle, and long versions of the questionnaire. The aim of the present article is to present and test the reliability of the new international middle version of the COPSOQ III. Methods: The questionnaire was tested among 23,361 employees during 2016-2017 in Canada, Spain, France, Germany, Sweden, and Turkey. A total of 26 dimensions (measured through scales or single items) of the middle version and two from the long version were tested. Psychometric properties of the dimensions were assessed regarding reliability (Cronbach α), ceiling and floor effects (fractions with extreme answers), and distinctiveness (correlations with other dimensions). Results: Most international middle dimensions had satisfactory reliability in most countries, though some ceiling and floor effects were present. Dimensions with missing values were rare. Most dimensions had low to medium intercorrelations. Conclusions: The COPSOQ III offers reliable and distinct measures of a wide range of psychosocial dimensions of modern working life in different countries; although a few measures could be improved. Future testing should focus on validation of the COPSOQ items and dimensions using both qualitative and quantitative approaches. Such investigations would enhance the basis for recommendations using the COPSOQ III.

Managing the Mix of Sport and Social Capital: A Study of Local Networks in the Belgian Homeless Football Cup

Elien Claes,Chris Heim,Bart Vanreusel,Hanne Vandermeerschen,Jeroen Scheerder 글로벌지식마케팅경영학회 2020 Journal of Global Sport Management Vol.5 No.3

In this study, local networks surrounding the 11 homeless teams of the Belgian Homeless Football Cup (BHFC), a social football project for socially excluded homeless people, are analyzed from an organizational social capital perspective. Semi-structured interviews with key representatives within the local networks (including social, football, and government-related partners) were conducted. An organizational analysis is performed to explore the composition of the different networks, and to identify significant actors. Facilitating and constraining circumstances in sport for social change projects, like the BHFC, are examined. The features and conditions of the networks revealed in this study are of relevance for field workers and policy-makers and can be key factors for the management of sport for social change projects. This knowledge contributes to the sustainability and stability of the networks, and of the projects for social change in which these networks are embedded.

Nanomedicine-based antimicrobial peptide delivery for bacterial infections: recent advances and future prospects

Thapa Raj Kumar,Diep Dzung B.,Tønnesen Hanne Hjorth 한국약제학회 2021 Journal of Pharmaceutical Investigation Vol.51 No.4

Background Antimicrobial peptides (AMPs) have gained wide interest as viable alternatives to antibiotics owing to their potent antimicrobial effects and the low propensity of resistance development. However, their physicochemical properties (solubility, charge, hydrophobicity/hydrophilicity), stability issues (proteolytic or enzymatic degradation, aggregation, chemical degradation), and toxicities (interactions with blood components or cellular toxicities) limit their therapeutic applications. Area covered Nanomedicine-based therapeutic delivery is an emerging concept. The AMP loaded nanoparticles have been prepared and investigated for their antimicrobial effects. In this review, we will discuss different nanomedicine-based AMP delivery systems including metallic nanoparticles, lipid nanoparticles, polymeric nanoparticles, and their hybrid systems along with their future prospects for potent antimicrobial efficacy. Expert opinion Nanomedicine-based AMP delivery is a recent approach to the treatment of bacterial infections. The advantageous properties of nanoparticles including the enhancement of AMP stability, controlled release, and targetability make them suitable for the augmentation of AMP activity. Modifications in the nanomedicine-based approach are required to overcome the problems of nanoparticle instability, shorter residence time, and toxicity. Future rigorous studies for both the AMP loaded nanoparticle preparation and characterization, and detailed evaluations of their in vitro and in vivo antimicrobial effects and toxicities, are essential.

Early Assessment of the Risk for Gestational Diabetes Mellitus: Can Fasting Parameters of Glucose Metabolism Contribute to Risk Prediction?

Veronica Falcone,Grammata Kotzaeridi,Melanie Hanne Breil,Ingo Rosicky,Tina Stopp,Gülen Yerlikaya-Schatten,Michael Feichtinger,Wolfgang Eppel,Peter Husslein,Andrea Tura,Christian S. Göbl 대한당뇨병학회 2019 Diabetes and Metabolism Journal Vol.43 No.6

Background: An early identification of the risk groups might be beneficial in reducing morbidities in patients with gestational diabetes mellitus (GDM). Therefore, this study aimed to assess the biochemical predictors of glycemic conditions, in addition to fasting indices of glucose disposal, to predict the development of GDM in later stage and the need of glucose-lowering medication. Methods: A total of 574 pregnant females (103 with GDM and 471 with normal glucose tolerance [NGT]) were included. A metabolic characterization was performed before 15+6 weeks of gestation by assessing fasting plasma glucose (FPG), fasting insulin (FI), fasting C-peptide (FCP), and glycosylated hemoglobin (HbA1c). Thereafter, the patients were followed-up until the delivery. Results: Females with NGT had lower levels of FPG, FI, FCP, or HbA1c at the early stage of pregnancy, and therefore, showed an improved insulin action as compared to that in females who developed GDM. Higher fasting levels of FPG and FCP were associated with a higher risk of developing GDM. Moreover, the predictive accuracy of this metabolic profiling was also good to distinguish the patients who required glucose-lowering medications. Indices of glucose disposal based on C-peptide improved the predictive accuracy compared to that based on insulin. A modified quantitative insulin sensitivity check index (QUICKIc) showed the best differentiation in terms of predicting GDM (area under the receiver operating characteristics curve [ROC-AUC], 72.1%) or need for pharmacotherapy (ROC-AUC, 83.7%). Conclusion: Fasting measurements of glucose and C-peptide as well as the surrogate indices of glycemic condition could be used for stratifying pregnant females with higher risk of GDM at the beginning of pregnancy.