Jitka Eberová

Inserm

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Sergii Kolodych

Laboratoire de Chémo-biologie synthétique et thérapeutique

Alain Wagner

Université de Strasbourg

Oleksandr Koniev

Laboratoire de Chémo-biologie synthétique et thérapeutique

Sarah Cianférani

Université de Strasbourg

M Jirsa

Institute of Clinical and Experimental Medicine

Sébastien Papot

Institut de Chimie des Milieux et des Matériaux de Poitiers

Brigitte Renoux

Institut de Chimie des Milieux et des Matériaux de Poitiers

Anthony Ehkirch

Université de Strasbourg

Chloé Michel

Martin Hřebı́ček

Charles University

Cooperative Institutions

Centre National de la Recherche Scientifique

Charles University

Université de Strasbourg

Inserm

General University Hospital in Prague

ESPCI Paris

Université Paris Sciences et Lettres

Institut de génétique et de biologie moléculaire et cellulaire

Institut Pluridisciplinaire Hubert Curien

Institut de Biologie Moléculaire et Cellulaire

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Urinary and fecal immunoglobulin A, cortisol and 11‐17 dioxoandrostanes, and serum cortisol in metabolic cage housed female cynomolgus monkeys (Macaca fascicularis)

Journal of Medical Primatology (2007)

Yasmina Arditi Paramastri Félix Royo Jitka Eberová Hans‐Erik Carlsson Dondin Sajuthi

Abstract Background and methods Quantitative enzyme‐immunoassays of urinary and fecal immunoglobulin A (IgA), cortisol and 11‐17‐dioxoandrostanes (11,17‐DOA), and serum cortisol in eight metabolic‐cage‐housed female cynomolgus monkeys were performed. The monkeys were divided into two groups, B and NB. Group B animals were blood sampled every 6 hours, whereas Group NB animals were not handled/blood sampled. Results No differences were recorded between the amounts of feces and urine excreted by the two groups. Group B animals excreted more urinary cortisol than did Group NB animals indicating that restraint‐blood sampling resulted in a stress response. Excreted amounts of IgA and 11,17‐DOA (urine and feces) did not differ between the groups. Conclusions Urinary cortisol was a reliable marker of the stress associated with repeated blood sampling. Declining amounts of excreted urinary cortisol indicated that cynomolgus monkeys acclimated quickly to repeated blood sampling in metabolism cages. Within and between animal variation in amounts of feces voided demonstrated the importance of expressing fecal markers as ‘amounts excreted per time unit per kg body weight’ rather than just measuring the concentrations in fecal samples.

Blood sampling

Cage

10.1111/j.1600-0684.2007.00229.x

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Citations (29)

Development and evaluation of β-galactosidase-sensitive antibody-drug conjugates

European Journal of Medicinal Chemistry (2017)

Sergii Kolodych Chloé Michel Sébastien Delacroix Oleksandr Koniev Anthony Ehkirch

Antibody-drug conjugate

Conjugate

Trastuzumab emtansine

Linker

10.1016/j.ejmech.2017.08.008

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Citations (44)

Histone Methyltransferase DOT1L Drives Recovery of Gene Expression after a Genotoxic Attack

PLoS Genetics (2013)

Valentyn Oksenych Alexander S. Zhovmer Salim Ziani Pierre‐Olivier Mari Jitka Eberová

UV-induced DNA damage causes repression of RNA synthesis. Following the removal of DNA lesions, transcription recovery operates through a process that is not understood yet. Here we show that knocking-out of the histone methyltransferase DOT1L in mouse embryonic fibroblasts (MEF(DOT1L)) leads to a UV hypersensitivity coupled to a deficient recovery of transcription initiation after UV irradiation. However, DOT1L is not implicated in the removal of the UV-induced DNA damage by the nucleotide excision repair pathway. Using FRAP and ChIP experiments we established that DOT1L promotes the formation of the pre-initiation complex on the promoters of UV-repressed genes and the appearance of transcriptionally active chromatin marks. Treatment with Trichostatin A, relaxing chromatin, recovers both transcription initiation and UV-survival. Our data suggest that DOT1L secures an open chromatin structure in order to reactivate RNA Pol II transcription initiation after a genotoxic attack.

Trichostatin A

RNA polymerase II

Transcription

Epigenomics

10.1371/journal.pgen.1003611

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Citations (78)

MAPN: First-in-Class Reagent for Kinetically Resolved Thiol-to-Thiol Conjugation

Bioconjugate Chemistry (2015)

Oleksandr Koniev Sergii Kolodych Zoljargal Baatarkhuu Johann Stojko Jitka Eberová

Thiols are among the most frequently used functional groups in the field of bioconjugation. While there exists a variety of heterobifunctional reagents that allow for coupling thiols to other functions (e.g., amines, carboxylic acids), there is no specific reagent for creating heteroconjugates using two different thiols. In response to the ever-increasing demand for bioconjugation tools, we have developed p-(maleimide)-phenylpropionitrile (MAPN)—an efficient reagent for kinetically resolved thiol-to-thiol coupling. In a comparative study with its closest commercially available analogue, p-phenylenedimaleimide, MAPN has shown substantial advantages for the preparation of thiol–thiol heteroconjugates. Namely, an antibody–drug conjugate (ADC) with mertansine (DM1), conjugated to the cysteine residues of Trastuzumab, was prepared for the first time.

Bioconjugation

Thiol

Conjugate

Maleimide

10.1021/acs.bioconjchem.5b00440

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Disruption of OTC promoter-enhancer interaction in a patient with symptoms of ornithine carbamoyltransferase deficiency

Human Mutation (2010)

Ondřej Lukšan M Jirsa Jitka Eberová Jakub Minks Helena Trešlová

In a female patient with signs of ornithine carbamoyltransferase deficiency (OTCD), the only variation found was a heterozygous single nucleotide substitution c.-366A>G. Determination of transcription start sites of human OTC 95, 119 and 169 bp upstream of the initiation codon located the variation upstream of the 5'-untranslated region. We predicted the human promoter and enhancer elements from homology with rat and mouse, performed function analysis of both regulatory regions and assessed the impact of the promoter variation in functional studies using dual luciferase reporter assay. Our data indicate that: (i) Full transcriptional activity of human OTC promoter depends on an upstream enhancer, as do the rodent promoters. (ii) The promoter variation c.-366A>G does not affect the function of the promoter alone but it disrupts the interaction of the promoter with the enhancer. (iii) The promoter – enhancer interaction contribute to tissue specific expression of OTC in the liver. We conclude that mutations in the regulatory regions of OTC can lead to OTCD and should be included in genetic testing. © 2010 Wiley-Liss, Inc.

Ornithine Carbamoyltransferase

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10.1002/humu.21215

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Citations (18)

Glucocerebrosidase gene has an alternative upstream promoter, which has features and expression characteristic of housekeeping genes

Blood Cells Molecules and Diseases (2011)

Eva Svobodová Lenka Mrázová Ondřej Lukšan Deborah Elstein Ari Zimran

Housekeeping gene

TATA box

CpG site

Upstream activating sequence