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Artigo Acesso aberto Revisado por pares

Lenno Krenning, Stijn Sonneveld, Marvin E. Tanenbaum,

Accurate control of the cell cycle is critical for development and tissue homeostasis, and requires precisely timed expression of many genes. Cell cycle gene expression is regulated through transcriptional and translational control, as well as through regulated protein degradation. Here, we show that widespread and temporally controlled mRNA decay acts as an additional mechanism for gene expression regulation during the cell cycle in human cells. We find that two waves of mRNA decay occur sequentially ...

Tópico(s): Genomics and Chromatin Dynamics

2022 - eLife Sciences Publications Ltd | eLife

Artigo Acesso aberto Revisado por pares

S. Ortega, Lenno van den Berg, Mario Pronk, Merle de Kreuk,

In aerobic granular sludge (AGS) reactors, granules of different sizes coexist in a single reactor. Their differences in settling behaviour cause stratification in the settled granule bed. In combination with substrate concentration gradients over the reactor height during the anaerobic plug-flow feeding regime, this can result in functional differences between granule sizes. In this study, we compared the hydrolytic activity in granules of 4 size ranges (between 0.5 and 4.8 mm diameter) collected ...

Tópico(s): Anaerobic Digestion and Biogas Production

2022 - Elsevier BV | Water Research X

Artigo Acesso aberto Revisado por pares

Anoek Friskes, Lisa Koob, Lenno Krenning, Tesa Severson, Emma S. Koeleman, Xabier Vergara, Michaël Schubert, Jeroen van den Berg, Bastiaan Evers, Anna G. Manjón, Stacey E. P. Joosten, Yongsoo Kim, Wilbert Zwart, René H. Medema,

Cells respond to double-strand breaks (DSBs) by activating DNA damage response pathways, including cell cycle arrest. We have previously shown that a single double-strand break generated via CRISPR/Cas9 is sufficient to delay cell cycle progression and compromise cell viability. However, we also found that the cellular response to DSBs can vary, independent of the number of lesions. This implies that not all DSBs are equally toxic, and raises the question if the location of a single double-strand ...

Tópico(s): Genomics and Chromatin Dynamics

2022 - Oxford University Press | Nucleic Acids Research

Artigo Acesso aberto Revisado por pares

Apostolos Menegakis, Rob Klompmaker, Claire Vennin, Aina Arbusà, Maartje P. F. Damen, Bram van den Broek, Daniel Zips, Jacco van Rheenen, Lenno Krenning, René H. Medema,

Double strand breaks (DSBs) are highly toxic to a cell, a property that is exploited in radiation therapy. A critical component for the damage induction is cellular oxygen, making hypoxic tumor areas refractory to the efficacy of radiation treatment. During a fractionated radiation regimen, these hypoxic areas can be re-oxygenated. Nonetheless, hypoxia still constitutes a negative prognostic factor for the patient’s outcome. We hypothesized that this might be attributed to specific hypoxia-induced ...

Tópico(s): Effects of Radiation Exposure

2021 - Multidisciplinary Digital Publishing Institute | Cells

Artigo Acesso aberto Revisado por pares

Marten Hornsveld, Femke M. Feringa, Lenno Krenning, Jeroen van den Berg, Lydia M.M. Smits, Nguyen B.T. Nguyen, Maria J. Rodríguez Colman, Tobias B. Dansen, René H. Medema, Boudewijn Burgering,

DNA replication is challenged by numerous exogenous and endogenous factors that can interfere with the progression of replication forks. Substantial accumulation of single-stranded DNA during DNA replication activates the DNA replication stress checkpoint response that slows progression from S/G2 to M phase to protect genomic integrity. Whether and how mild replication stress restricts proliferation remains controversial. Here, we identify a cell cycle exit mechanism that prevents S/G2 phase arrested ...

Tópico(s): Microtubule and mitosis dynamics

2021 - Cell Press | Cell Reports

Artigo Acesso aberto Revisado por pares

Lenno van den Berg, Mario Pronk, Mark C.M. van Loosdrecht, Merle de Kreuk,

Granular sludge processes are frequently used in domestic and industrial wastewater treatment. The granule buoyant density and biomass density are important parameters for the design and operation of granular sludge reactors. Different methods to measure the granule density include the pycnometer method, the Percoll density gradient method, the dextran blue method, and the settling velocity method. In this study, a comparison was made between these four methods to measure granule density for granules ...

Tópico(s): Membrane Separation Technologies

2021 - Taylor & Francis | Environmental Technology

Artigo Acesso aberto Revisado por pares

Marco Jost, Yuwen Chen, Luke A. Gilbert, Max A. Horlbeck, Lenno Krenning, Grégory Menchon, Ankit Rai, Min Y. Cho, Jacob J. Stern, A.E. Prota, Martin Kampmann, Anna Akhmanova, Michel O. Steinmetz, Marvin E. Tanenbaum, Jonathan S. Weissman,

We recently used CRISPRi/a-based chemical-genetic screens and cell biological, biochemical, and structural assays to determine that rigosertib, an anti-cancer agent in phase III clinical trials, kills cancer cells by destabilizing microtubules. Reddy and co-workers (Baker et al., 2020Baker S.J. Cosenza S.C. Athuluri-Divakar S. Reddy M.V.R. Vasquez-Del Carpio R. Jain R. Aggarwal A.K. Reddy E.P. A Contaminant Impurity, Not Rigosertib, Is a Tubulin Binding Agent.Mol. Cell. 2020; 79 (this issue): 180- ...

Tópico(s): Cancer Treatment and Pharmacology

2020 - Elsevier BV | Molecular Cell

Artigo Revisado por pares

Nico Battich, Joep Beumer, Buys de Barbanson, Lenno Krenning, Chloé S. Baron, Marvin E. Tanenbaum, Hans Clevers, Alexander van Oudenaarden,

RNA life span at single-cell resolution RNA transcripts are an easily accessed representation of gene expression, but we lack a comprehensive view of the life span of RNA within the single cell. Battich et al. developed a method to sequence messenger RNA labeled with 5-ethynyl-uridine (EU) in single cells (scEU-seq), which allows estimation of RNA transcription and degradation rates. When examining intestinal organoid cells, scEU-seq data can be used to discern between transcription and degradation ...

Tópico(s): Single-cell and spatial transcriptomics

2020 - American Association for the Advancement of Science | Science

Artigo Revisado por pares

Karsten Stæhr, Lenno Uusküla,

Purpose Large or increasing stocks of non-performing loans in the banking sector constitute threats to financial stability. This paper considers to which extent various macroeconomic and macro-financial factors may serve as leading indicators for the dynamics of the ratio of non-performing loans to total loans. Design/methodology/approach The paper estimates panel data models for all EU countries and two groups of EU countries using quarterly data over approximately 20 years. Findings The estimations ...

Tópico(s): Housing Market and Economics

2020 - Emerald Publishing Limited | Journal of Economic Studies

Artigo Acesso aberto Revisado por pares

Lenno van den Berg, Catherine M. Kirkland, Joseph D. Seymour, Sarah L. Codd, Mark C.M. van Loosdrecht, Merle de Kreuk,

Abstract Aerobic granular sludge (AGS) technology allows simultaneous nitrogen, phosphorus, and carbon removal in compact wastewater treatment processes. To operate, design, and model AGS reactors, it is essential to properly understand the diffusive transport within the granules. In this study, diffusive mass transfer within full‐scale and lab‐scale AGS was characterized with nuclear magnetic resonance (NMR) methods. Self‐diffusion coefficients of water inside the granules were determined with pulsed‐ ...

Tópico(s): Membrane Separation Technologies

2020 - Wiley | Biotechnology and Bioengineering

Artigo Acesso aberto Revisado por pares

Lenno van den Berg, Mark C.M. van Loosdrecht, Merle de Kreuk,

Biofilm and granular sludge processes depend on diffusion of substrates. Despite their importance for the kinetic description of biofilm reactors, biofilm diffusion coefficients reported in literature vary greatly. The aim of this simulation study was to determine to what extent the methods that are used to measure diffusion coefficients contribute to the reported variability. Granular sludge was used as a case study. Six common methods were selected, based on mass balances and microelectrodes. ...

Tópico(s): Recycled Aggregate Concrete Performance

2020 - Wiley | Biotechnology and Bioengineering

Revisão Acesso aberto Revisado por pares

Lenno Krenning, Jeroen van den Berg, René H. Medema,

DNA double-strand breaks (DSBs) pose a constant threat to genomic integrity. Such DSBs need to be repaired to preserve homeostasis at both the cellular and organismal levels. Hence, the DNA damage response (DDR) has evolved to repair these lesions and limit their toxicity. The initiation of DNA repair depends on the activation of the DDR, and we know that the strength of DDR signaling may differentially affect cellular viability. However, we do not fully understand what determines the cytotoxicity ...

Tópico(s): Traumatic Brain Injury Research

2019 - Elsevier BV | Molecular Cell

Artigo Acesso aberto Revisado por pares

Femke M. Feringa, Jonne A. Raaijmakers, Michael A. Hadders, Chantal Vaarting, Libor Macůrek, Luuk Heitink, Lenno Krenning, René H. Medema,

Abstract Double-stranded DNA breaks activate a DNA damage checkpoint in G2 phase to trigger a cell cycle arrest, which can be reversed to allow for recovery. However, damaged G2 cells can also permanently exit the cell cycle, going into senescence or apoptosis, raising the question how an individual cell decides whether to recover or withdraw from the cell cycle. Here we find that the decision to withdraw from the cell cycle in G2 is critically dependent on the progression of DNA repair. We show ...

Tópico(s): CRISPR and Genetic Engineering

2018 - Nature Portfolio | Nature Communications

Artigo Acesso aberto Revisado por pares

Mar Soto, Iraia García‐Santisteban, Lenno Krenning, René H. Medema, Jonne A. Raaijmakers,

ABSTRACT DNA in micronuclei is likely to get damaged. When shattered DNA from micronuclei gets reincorporated into the primary nucleus, aberrant rearrangements can take place, a phenomenon referred to as chromothripsis. Here, we investigated how chromatids from micronuclei act in subsequent divisions and how this affects their fate. We observed that the majority of chromatids derived from micronuclei fail to establish a proper kinetochore in mitosis, which is associated with problems in chromosome ...

Tópico(s): DNA and Nucleic Acid Chemistry

2018 - The Company of Biologists | Journal of Cell Science

Artigo Acesso aberto Revisado por pares

Marco Jost, Yuwen Chen, Luke A. Gilbert, Max A. Horlbeck, Lenno Krenning, Grégory Menchon, Ankit Rai, Min Y. Cho, Jacob J. Stern, A.E. Prota, Martin Kampmann, Anna Akhmanova, Michel O. Steinmetz, Marvin E. Tanenbaum, Jonathan S. Weissman,

Chemical libraries paired with phenotypic screens can now readily identify compounds with therapeutic potential. A central limitation to exploiting these compounds, however, has been in identifying their relevant cellular targets. Here, we present a two-tiered CRISPR-mediated chemical-genetic strategy for target identification: combined genome-wide knockdown and overexpression screening as well as focused, comparative chemical-genetic profiling. Application of these strategies to rigosertib, a drug ...

Tópico(s): PI3K/AKT/mTOR signaling in cancer

2017 - Elsevier BV | Molecular Cell

Artigo Acesso aberto Revisado por pares

Femke M. Feringa, Lenno Krenning, André Koch, Jeroen van den Berg, Bram van den Broek, Kees Jalink, René H. Medema,

Abstract Activation of the DNA-damage response can lead to the induction of an arrest at various stages in the cell cycle. These arrests are reversible in nature, unless the damage is too excessive. Here we find that checkpoint reversibility is lost in cells that are in very late G2, but not yet fully committed to enter mitosis (antephase). We show that antephase cells exit the cell cycle and enter senescence at levels of DNA damage that induce a reversible arrest in early G2. We show that checkpoint ...

Tópico(s): Genomics and Chromatin Dynamics

2016 - Nature Portfolio | Nature Communications

Revisão Acesso aberto Revisado por pares

Indra A. Shaltiël, Lenno Krenning, Wytse Bruinsma, René H. Medema,

Cell cycle checkpoints activated by DNA double-strand breaks (DSBs) are essential for the maintenance of the genomic integrity of proliferating cells. Following DNA damage, cells must detect the break and either transiently block cell cycle progression, to allow time for repair, or exit the cell cycle. Reversal of a DNA-damage-induced checkpoint not only requires the repair of these lesions, but a cell must also prevent permanent exit from the cell cycle and actively terminate checkpoint signalling ...

Tópico(s): Cancer-related Molecular Pathways

2015 - The Company of Biologists | Journal of Cell Science

Artigo Acesso aberto Revisado por pares

Gertrud Errit, Lenno Uusküla,

This paper studies the effect of a monetary policy shock in the euro area on the main Estonian economic and financial variables between 2000 and 2012. Using a standard structural vector autoregression (SVAR) model we find strong and persistent effects on Estonian GDP, private consumption, corporate investment, and imports. A monetary policy shock also has strong and sluggish effects on the housing loan and consumer credit interest rates. The estimated reaction of Estonian GDP and the GDP deflator- ...

Tópico(s): Fiscal Policies and Political Economy

2014 - Taylor & Francis | Baltic Journal of Economics

Artigo Acesso aberto Revisado por pares

Lenno Krenning, Femke M. Feringa, Indra A. Shaltiël, Jeroen van den Berg, René H. Medema,

DNA damage can result in a transient cell-cycle arrest or lead to permanent cell-cycle withdrawal. Here we show that the decision to irreversibly withdraw from the cell cycle is made within a few hours following damage in G2 cells. This permanent arrest is dependent on induction of p53 and p21, resulting in the nuclear retention of Cyclin B1. This rapid response is followed by the activation of the APC/C(Cdh1) (the anaphase-promoting complex/cyclosome and its coactivator Cdh1) several hours later. ...

Tópico(s): Pluripotent Stem Cells Research

2014 - Elsevier BV | Molecular Cell

Artigo Revisado por pares

Michael Ehrmann, Chiara Osbat, Jan Stráský, Lenno Uusküla,

This paper studies the determinants of the euro exchange rate volatility during the European sovereign debt crisis, allowing a role for macroeconomic fundamentals, policy actions and the public debate by policy makers. It finds that the euro exchange rate mainly danced to its own tune, with a particularly low explanatory power for macroeconomic fundamentals. The findings of the paper also suggest that financial markets might have been less reactive to the public debate by policy makers than previously ...

Tópico(s): Market Dynamics and Volatility

2014 - Elsevier BV | Journal of International Money and Finance

Artigo

Michael Ehrmann, Chiara Osbat, Jan Stráský, Lenno Uusküla,

This paper studies the determinants of the euro exchange rate during the European sovereign debt crisis, allowing a role for macroeconomic fundamentals, policy actions and the public debate by policy makers. It finds that the euro exchange rate mainly danced to its own tune, with a particularly low explanatory power for macroeconomic fundamentals. Among the few factors that are found to have affected changes in exchanges rate levels are policy actions at the EU level and by the ECB. The findings ...

Tópico(s): European Monetary and Fiscal Policies

2013 - RELX Group (Netherlands) | SSRN Electronic Journal

Artigo Acesso aberto Revisado por pares

L.C.G. van den Einden, Mieke G.J. te Kolste, A.L.M. Lagro‐Janssen, Lenno Dukel,

To determine how often medical students are not allowed to perform gynecological examinations during their obstetrics-gynecology clerkship, identify the barriers to participation related to physicians and patients, explore the role of the supervisory physician in not allowing medical student involvement, and explore differences between male and female students' experiences.All medical students entering their obstetrics-gynecology clerkship at a medical school in the Netherlands between May and October ...

Tópico(s): Simulation-Based Education in Healthcare

2013 - Lippincott Williams & Wilkins | Academic Medicine

Artigo Acesso aberto Revisado por pares

Julien Espeut, Dhanya K. Cheerambathur, Lenno Krenning, Karen Oegema, Arshad Desai,

Accurate chromosome segregation requires coordination between microtubule attachment and spindle checkpoint signaling at the kinetochore. The kinetochore-localized KMN (KNL-1/Mis12 complex/Ndc80 complex) network, which mediates microtubule attachment and scaffolds checkpoint signaling, harbors two distinct microtubule-binding activities: the load-bearing activity of the Ndc80 complex and a less well-understood activity in KNL-1. In this paper, we show that KNL-1 microtubule-binding and -bundling activity ...

Tópico(s): Ubiquitin and proteasome pathways

2012 - Rockefeller University Press | The Journal of Cell Biology

Artigo Acesso aberto Revisado por pares

Luís Pereira‐da‐Silva, AB Costa, Leonardo Lenno Lima Pereira, AF Filipe, Daniel Virella, Ernesto César Pinto Leal‐Junior, Ana Catarina Moreira, M de la Rosa, Lino Mendes, Micaela Serelha,

Very premature newborns have an increased risk of low bone mass and metabolic bone disease. Most longitudinal studies report a significant decline in bone strength in the first weeks after birth. The aim of the study was to evaluate whether higher early calcium (Ca) and phosphorus (P) intake delivered by parenteral nutrition (PN) can prevent bone strength decline in preterm infants, within the first weeks after birth.This was a randomized controlled trial of consecutively admitted neonates born with ≤ ...

Tópico(s): Neonatal Respiratory Health Research

2011 - Lippincott Williams & Wilkins | Journal of Pediatric Gastroenterology and Nutrition

Artigo Acesso aberto Revisado por pares

Mónica Álvarez‐Fernández, Vincentius A. Halim, Lenno Krenning, Melinda Aprelia, Shabaz Mohammed, Albert J. R. Heck, René H. Medema,

Activation of the DNA‐damage checkpoint culminates in the inhibition of cyclin‐dependent kinase (Cdk) complexes to prevent cell‐cycle progression. We have shown recently that Cdk activity is required for activation of the Forkhead transcription factor FoxM1, an important regulator of gene expression in the G2 phase of the cell cycle. Here, we show that FoxM1 is transcriptionally active during a DNA‐damage‐induced G2 arrest and is essential for checkpoint recovery. Paradoxically, Cdk activity, although ...

Tópico(s): FOXO transcription factor regulation

2010 - Springer Nature | EMBO Reports

Artigo Acesso aberto Revisado por pares

Morten O. Ravn, Stephanie Schmitt‐Grohé, Martı ́n Uribe, Lenno Uusküla,

We introduce deep habits into a sticky-price sticky-wage economy and examine the resulting models ability to account for the impact of monetary policy shocks. The deep habits mechanism gives rise to countercyclical markup movements even when prices are flexible and interacts with nominal rigidities in interesting ways. Key parameters are estimated using a limited information approach. The deep habits model can account very precisely for the persistent impact of monetary policy shocks on aggregate ...

Tópico(s): Financial Markets and Investment Strategies

2009 - Elsevier BV | Journal of the Japanese and International Economies

Artigo Revisado por pares

E.J. Meijers-Heijboer, L.C. Verhoog, CTM Brekelmans, Caroline Seynaeve, MMA Tilanus-Linthorst, Anja Wagner, Lenno Dukel, Peter Devilee, AMW van den Ouweland, AN van Geel, J.G.M. Klijn,

Background Germline mutations in the BRCA1 and BRCA2 genes highly predispose to breast and ovarian cancer. In families with BRCA1 or BRCA2 mutations, identification of mutation carriers is clinically relevant in view of the options for surveillance and prevention. Methods We assessed presymptomatic DNA testing and prophylactic surgery in 53 consecutive families presenting to the Rotterdam Family Cancer Clinic with a known BRCA1 or BRCA2 mutation. We identified predictors for DNA testing and prophylactic ...

Tópico(s): DNA Repair Mechanisms

2000 - Elsevier BV | The Lancet

Artigo Revisado por pares

Marlies E de Groot, Lenno Dukel, Savi Chadha‐Ajwani, Herold J. Metselaar, Hugo W. Tilanus, Frans J.M. Huikeshoven,

Case report of a 47-year-old woman with a mass in the lower abdomen, was referred to us by the surgeon, two years after orthotopic liver transplantation for hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP), which was elevated at the time of initial diagnosis, was in the normal range. Frozen section examination during exploratory laparotomy showed appearances consistent with metastatic HCC in the ovary. This was confirmed at the final pathological examination. Definitive pathological conclusions ...

Tópico(s): Renal and related cancers

2000 - Elsevier BV | European Journal of Obstetrics & Gynecology and Reproductive Biology

Artigo Revisado por pares

Andreas Goldbach, Marie‐Louise Saboungi, Lennos Iton, David L. Price,

A. Goldbach, M. Saboungi, L. Iton and D. L. Price, Chem. Commun., 1999, 997 DOI: 10.1039/A900253G

Tópico(s): Phase-change materials and chalcogenides

1999 - Royal Society of Chemistry | Chemical Communications