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Article ; Online: Concise Review

Laura Simons / Marina Cavazzana / Isabelle André

Stem Cells Translational Medicine, Vol 8, Iss 7, Pp 650-

Boosting T‐Cell Reconstitution Following Allogeneic Transplantation—Current Concepts and Future Perspectives

2019 Volume 657

Abstract: Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for a large number of malignant and nonmalignant (inherited) diseases of the hematopoietic system. Nevertheless, non‐HLA identical transplantations are ... ...

Abstract	Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for a large number of malignant and nonmalignant (inherited) diseases of the hematopoietic system. Nevertheless, non‐HLA identical transplantations are complicated by a severe T‐cell immunodeficiency associated with a high rate of infection, relapse and graft‐versus‐host disease. Initial recovery of T‐cell immunity following HSCT relies on peripheral expansion of memory T cells mostly driven by cytokines. The reconstitution of a diverse, self‐tolerant, and naive T‐cell repertoire, however, may take up to 2 years and crucially relies on the interaction of T‐cell progenitors with the host thymic epithelium, which may be altered by GvHD, age or transplant‐related toxicities. In this review, we summarize current concepts to stimulate reconstitution of a peripheral and polyclonal T‐cell compartment following allogeneic transplantation such as graft manipulation (i.e., T‐cell depletion), transfusion of ex vivo manipulated donor T cells or the exogenous administration of cytokines and growth factors to stimulate host‐thymopoiesis with emphasis on approaches which have led to clinical trials. Particular attention will be given to the development of cellular therapies such as the ex vivo generation of T‐cell precursors to fasten generation of a polyclonal and functional host‐derived T‐cell repertoire. Having been tested so far only in preclinical mouse models, clinical studies are now on the way to validate the efficacy of such T‐cell progenitors in enhancing immune reconstitution following HSCT in various clinical settings. Stem Cells Translational Medicine 2019;00:1–8
Keywords	Cellular therapy ; Hematopoietic stem cell transplantation ; Immunodeficiency ; Immune reconstitution ; T‐cell ; Thymus ; Medicine (General) ; R5-920 ; Cytology ; QH573-671
Subject code	610
Language	English
Publishing date	2019-07-01T00:00:00Z
Publisher	Oxford University Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Combining multi-scale modelling methods to decipher molecular motions of a branching sucrase from glycoside-hydrolase family 70.

Akli Ben Imeddourene / Jérémy Esque / Isabelle André

PLoS ONE, Vol 13, Iss 8, p e

2018 Volume 0201323

Abstract: Among α-transglucosylases from Glycoside-Hydrolase family 70, the ΔN123-GB-CD2 enzyme derived from the bifunctional DSR-E from L. citreum NRRL B-1299 is particularly interesting as it was the first described engineered Branching Sucrase, not able to ... ...

Abstract	Among α-transglucosylases from Glycoside-Hydrolase family 70, the ΔN123-GB-CD2 enzyme derived from the bifunctional DSR-E from L. citreum NRRL B-1299 is particularly interesting as it was the first described engineered Branching Sucrase, not able to elongate glucan polymers from sucrose substrate. The previously reported overall structural organization of this multi-domain enzyme is an intricate U-shape fold conserved among GH70 enzymes which showed a certain conformational variability of the so-called domain V, assumed to play a role in the control of product structures, in available X-ray structures. Understanding the role of functional dynamics on enzyme reaction and substrate recognition is of utmost interest although it remains a challenge for biophysical methods. By combining long molecular dynamics simulation (1μs) and multiple analyses (NMA, PCA, Morelet Continuous Wavelet Transform and Cross Correlations Dynamics), we investigated here the dynamics of ΔN123-GB-CD2 alone and in interaction with sucrose substrate. Overall, our results provide the detailed picture at atomic level of the hierarchy of motions occurring along different timescales and how they are correlated, in agreement with experimental structural data. In particular, detailed analysis of the different structural domains revealed cooperative dynamic behaviors such as twisting, bending and wobbling through anti- and correlated motions, and also two structural hinge regions, of which one was unreported. Several highly flexible loops surrounding the catalytic pocket were also highlighted, suggesting a potential role in the acceptor promiscuity of ΔN123-GBD-CD2. Normal modes and essential dynamics underlined an interesting two-fold dynamic of the catalytic domain A, pivoting about an axis splitting the catalytic gorge in two parts. The comparison of the conformational free energy landscapes using principal component analysis of the enzyme in absence or in presence of sucrose, also revealed a more harmonic basin when sucrose is bound with a ...
Keywords	Medicine ; R ; Science ; Q
Subject code	540
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Total enzymatic synthesis of cis-α-irone from a simple carbon source

Xixian Chen / Rehka T / Jérémy Esque / Congqiang Zhang / Sudha Shukal / Chin Chin Lim / Leonard Ong / Derek Smith / Isabelle André

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 10

Abstract: Retrosynthetic pathway design using promiscuous enzymes can provide a solution to the biosynthetic production of natural products. Here, the authors design a pathway for the production of cis-α-irone with a promiscuous methyltransferase using structure- ... ...

Abstract	Retrosynthetic pathway design using promiscuous enzymes can provide a solution to the biosynthetic production of natural products. Here, the authors design a pathway for the production of cis-α-irone with a promiscuous methyltransferase using structure-guided enzyme engineering strategies.
Keywords	Science ; Q
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Conformational Itinerary of Sucrose During Hydrolysis by Retaining Amylosucrase

Santiago Alonso-Gil / Joan Coines / Isabelle André / Carme Rovira

Frontiers in Chemistry, Vol

2019 Volume 7

Abstract: By means of QM(DFT)/MM metadynamics we have unraveled the hydrolytic reaction mechanism of Neisseria polysaccharea amylosucrase (NpAS), a member of GH13 family. Our results provide an atomistic picture of the active site reorganization along the ... ...

Abstract	By means of QM(DFT)/MM metadynamics we have unraveled the hydrolytic reaction mechanism of Neisseria polysaccharea amylosucrase (NpAS), a member of GH13 family. Our results provide an atomistic picture of the active site reorganization along the catalytic double-displacement reaction, clarifying whether the glycosyl-enzyme reaction intermediate features an α-glucosyl unit in an undistorted 4C1 conformation, as inferred from structural studies, or a distorted 1S3-like conformation, as expected from mechanistic analysis of glycoside hydrolases (GHs). We show that, even though the first step of the reaction (glycosylation) results in a 4C1 conformation, the α-glucosyl unit undergoes an easy conformational change toward a distorted conformation as the active site preorganizes for the forthcoming reaction step (deglycosylation), in which an acceptor molecule, i.e., a water molecule for the hydrolytic reaction, performs a nucleophilic attack on the anomeric carbon. The two conformations (4C1 ad E3) can be viewed as two different states of the glycosyl-enzyme intermediate (GEI), but only the E3 state is preactivated for catalysis. These results are consistent with the general conformational itinerary observed for α-glucosidases.
Keywords	glycoside hydrolases ; quantum mechanics/molecular mechanics ; double-displacement reaction ; ab initio molecular dynamics ; metadynamics ; conformational analysis ; Chemistry ; QD1-999
Subject code	540
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Redirecting substrate regioselectivity using engineered ΔN123-GBD-CD2 branching sucrases for the production of pentasaccharide repeating units of S. flexneri 3a, 4a and 4b haptens

Mounir Benkoulouche / Akli Ben Imeddourene / Louis-Antoine Barel / Guillaume Le Heiget / Sandra Pizzut / Hanna Kulyk / Floriant Bellvert / Sophie Bozonnet / Laurence A. Mulard / Magali Remaud-Siméon / Claire Moulis / Isabelle André

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 14

Abstract: Abstract The (chemo-)enzymatic synthesis of oligosaccharides has been hampered by the lack of appropriate enzymatic tools with requisite regio- and stereo-specificities. Engineering of carbohydrate-active enzymes, in particular targeting the enzyme ... ...

Abstract	Abstract The (chemo-)enzymatic synthesis of oligosaccharides has been hampered by the lack of appropriate enzymatic tools with requisite regio- and stereo-specificities. Engineering of carbohydrate-active enzymes, in particular targeting the enzyme active site, has notably led to catalysts with altered regioselectivity of the glycosylation reaction thereby enabling to extend the repertoire of enzymes for carbohydrate synthesis. Using a collection of 22 mutants of ΔN123-GBD-CD2 branching sucrase, an enzyme from the Glycoside Hydrolase family 70, containing between one and three mutations in the active site, and a lightly protected chemically synthesized tetrasaccharide as an acceptor substrate, we showed that altered glycosylation product specificities could be achieved compared to the parental enzyme. Six mutants were selected for further characterization as they produce higher amounts of two favored pentasaccharides compared to the parental enzyme and/or new products. The produced pentasaccharides were shown to be of high interest as they are precursors of representative haptens of Shigella flexneri serotypes 3a, 4a and 4b. Furthermore, their synthesis was shown to be controlled by the mutations introduced in the active site, driving the glucosylation toward one extremity or the other of the tetrasaccharide acceptor. To identify the molecular determinants involved in the change of ΔN123-GBD-CD2 regioselectivity, extensive molecular dynamics simulations were carried out in combination with in-depth analyses of amino acid residue networks. Our findings help to understand the inter-relationships between the enzyme structure, conformational flexibility and activity. They also provide new insight to further engineer this class of enzymes for the synthesis of carbohydrate components of bacterial haptens.
Keywords	Medicine ; R ; Science ; Q
Subject code	540
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Computer-aided engineering of a branching sucrase for the glucodiversification of a tetrasaccharide precursor of S. flexneri antigenic oligosaccharides

Mounir Benkoulouche / Akli Ben Imeddourene / Louis-Antoine Barel / Dorian Lefebvre / Mathieu Fanuel / Hélène Rogniaux / David Ropartz / Sophie Barbe / David Guieysse / Laurence A. Mulard / Magali Remaud-Siméon / Claire Moulis / Isabelle André

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 14

Abstract: Abstract Enzyme engineering approaches have allowed to extend the collection of enzymatic tools available for synthetic purposes. However, controlling the regioselectivity of the reaction remains challenging, in particular when dealing with carbohydrates ...

Abstract	Abstract Enzyme engineering approaches have allowed to extend the collection of enzymatic tools available for synthetic purposes. However, controlling the regioselectivity of the reaction remains challenging, in particular when dealing with carbohydrates bearing numerous reactive hydroxyl groups as substrates. Here, we used a computer-aided design framework to engineer the active site of a sucrose-active $$\mathrm{\alpha }$$ α -transglucosylase for the 1,2-cis-glucosylation of a lightly protected chemically synthesized tetrasaccharide, a common precursor for the synthesis of serotype-specific S. flexneri O-antigen fragments. By targeting 27 amino acid positions of the acceptor binding subsites of a GH70 branching sucrase, we used a RosettaDesign-based approach to propose 49 mutants containing up to 15 mutations scattered over the active site. Upon experimental evaluation, these mutants were found to produce up to six distinct pentasaccharides, whereas only two were synthesized by the parental enzyme. Interestingly, we showed that by introducing specific mutations in the active site of a same enzyme scaffold, it is possible to control the regiospecificity of the 1,2-cis glucosylation of the tetrasaccharide acceptor and produce a unique diversity of pentasaccharide bricks. This work offers novel opportunities for the development of highly convergent chemo-enzymatic routes toward S. flexneri haptens.
Keywords	Medicine ; R ; Science ; Q
Subject code	540
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Correction

Marie Hoarau / Yannick Malbert / Romain Irague / Christelle Hureau / Peter Faller / Emmanuel Gras / Isabelle André / Magali Remaud-Siméon

PLoS ONE, Vol 13, Iss 9, p e

A Robust and Efficient Production and Purification Procedure of Recombinant Alzheimers Disease Methionine-Modified Amyloid-β Peptides.

2018 Volume 0205048

Abstract: This corrects the article DOI:10.1371/journal.pone.0161209.]. ...

Abstract	[This corrects the article DOI:10.1371/journal.pone.0161209.].
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Les mutations foncières et immobilières au pays du Mont-Blanc entre 2001 et 2008

Sylvie Duvillard / Isabelle André-Poyaud / Antonin Lorioux

Revue de Géographie Alpine, Iss 98-

2011 Volume 2

Abstract: Cette contribution entend présenter un état des lieux des mutations foncières dans un espace touristique de haute-montagne. La priorité est donnée à l’observation, le texte s’appuyant sur une base de données nouvellement mise sur le marché de la ... ...

Abstract	Cette contribution entend présenter un état des lieux des mutations foncières dans un espace touristique de haute-montagne. La priorité est donnée à l’observation, le texte s’appuyant sur une base de données nouvellement mise sur le marché de la connaissance par le Notariat de France. Le géographe y trouve matière à réflexion. D’abord, la cartographie du montant des transactions débouche sur une typologie communale qu’il s’agit d’éclairer par des variables socio-qualitatives (origine géographique des individus). La fragmentation socio-spatiale est le résultat de systèmes d’échanges de bien-fonds qui révèlent deux processus résidentiels concurrents. L’article tend à montrer comment un tri sélectif s’opère entre communes, les unes se spécialisant dans l’accueil des populations locales, les autres rejetant à leur périphérie ces mêmes populations. L’observation, à cette échelle, des transactions immobilières, signale le décalage évident qui existe entre la demande locale potentielle et l’offre accessible. Ce sont autant d’éléments soumis à la sagacité des politiques dès lors qu’ils se préoccupent de la question de l’accès aux fonciers (terres et immeubles) des locaux et de la cohésion de leur territoire. The aim of this contribution is to present a summary of the changes in property ownership that have occurred in a tourist area in the high mountains. Priority is given in the text to the analysis of data by taking advantage of a database recently made available on the knowledge market by the Notarial Office of France (Notariat de France). The geographer will find in it matters to reflect upon. First of all, a communal pattern that is to be explained by social qualitative variables (geographical origin of the individuals) emerges from the mapping of the total transactions. The socio-spatial fragmentation is the result of exchange systems for properties that reveal two competing residential processes. The article aims to demonstrate how a selective sorting process operates between communes, one group specialising in welcoming local populations, the other group rejecting the same populations at their outskirts. The analysis of property transactions on this scale indicates the obvious adjustment that exists between potential local demand and accessible supply. These are among the many aspects subject to the wisdom of politicians since they are preoccupied with the question of access of the local population to property (land and buildings) and the cohesion of their region.
Keywords	property markets ; new residential areas ; exchange system ; accessible supply of property ; access of the local population to housing ; peri-tourist communes ; marchés immobiliers ; nouvelles résidentialités ; système d’échange ; offre immobilière accessible ; l’accès au logement des locaux ; communes péri touristiques ; Geography. Anthropology. Recreation ; G ; Physical geography ; GB3-5030
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Institut de Géographie Alpine
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Les mutations foncières et immobilières au pays du Mont-Blanc entre 2001 et 2008

Isabelle André-Poyaud / Sylvie Duvillard / Antonin Lorioux

Revue de Géographie Alpine, Vol 98, Iss

2011 Volume 2

Abstract: The aim of this contribution is to present a summary of the changes in property ownership that have occurred in a tourist area in the high mountains. Priority is given in the text to the analysis of data by taking advantage of a database recently made ... ...

Abstract	The aim of this contribution is to present a summary of the changes in property ownership that have occurred in a tourist area in the high mountains. Priority is given in the text to the analysis of data by taking advantage of a database recently made available on the knowledge market by the Notarial Office of France (Notariat de France). The geographer will find in it matters to reflect upon. First of all, a communal pattern that is to be explained by social qualitative variables (geographical origin of the individuals) emerges from the mapping of the total transactions. The socio-spatial fragmentation is the result of exchange systems for properties that reveal two competing residential processes. The article aims to demonstrate how a selective sorting process operates between communes, one group specialising in welcoming local populations, the other group rejecting the same populations at their outskirts. The analysis of property transactions on this scale indicates the obvious adjustment that exists between potential local demand and accessible supply. These are among the many aspects subject to the wisdom of politicians since they are preoccupied with the question of access of the local population to property (land and buildings) and the cohesion of their region.
Keywords	property markets ; new residential areas ; exchange system ; accessible supply of property ; access of the local population to housing ; peri-tourist communes ; Geography. Anthropology. Recreation ; G ; Physical geography ; GB3-5030
Subject code	910
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Institut de Géographie Alpine
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Land and property transfers in the Mont-Blanc region between and 2001 and 2008

Isabelle André-Poyaud / Sylvie Duvillard / Antonin Lorioux

Revue de Géographie Alpine , Iss 98-

2010 Volume 2

Abstract	The aim of this contribution is to present a summary of the changes in property ownership that have occurred in a tourist area in the high mountains. Priority is given in the text to the analysis of data by taking advantage of a database recently made available on the knowledge market by the Notarial Office of France (Notariat de France). The geographer will find in it matters to reflect upon. First of all, a communal pattern that is to be explained by social qualitative variables (geographical origin of the individuals) emerges from the mapping of the total transactions. The socio-spatial fragmentation is the result of exchange systems for properties that reveal two competing residential processes. The article aims to demonstrate how a selective sorting process operates between communes, one group specialising in welcoming local populations, the other group rejecting the same populations at their outskirts. The analysis of property transactions on this scale indicates the obvious adjustment that exists between potential local demand and accessible supply. These are among the many aspects subject to the wisdom of politicians since they are preoccupied with the question of access of the local population to property (land and buildings) and the cohesion of their region. Cette contribution entend présenter un état des lieux des mutations foncières dans un espace touristique de haute-montagne. La priorité est donnée à l’observation, le texte s’appuyant sur une base de données nouvellement mise sur le marché de la connaissance par le Notariat de France. Le géographe y trouve matière à réflexion. D’abord, la cartographie du montant des transactions débouche sur une typologie communale qu’il s’agit d’éclairer par des variables socio-qualitatives (origine géographique des individus). La fragmentation socio-spatiale est le résultat de systèmes d’échanges de bien-fonds qui révèlent deux processus résidentiels concurrents. L’article tend à montrer comment un tri sélectif s’opère entre communes, les unes se spécialisant dans l’accueil des populations locales, les autres rejetant à leur périphérie ces mêmes populations. L’observation, à cette échelle, des transactions immobilières, signale le décalage évident qui existe entre la demande locale potentielle et l’offre accessible. Ce sont autant d’éléments soumis à la sagacité des politiques dès lors qu’ils se préoccupent de la question de l’accès aux fonciers (terres et immeubles) des locaux et de la cohésion de leur territoire.
Keywords	property markets ; new residential areas ; exchange system ; accessible supply of property ; access of the local population to housing ; peri-tourist communes ; marchés immobiliers ; nouvelles résidentialités ; système d’échange ; offre immobilière accessible ; l’accès au logement des locaux ; communes péri touristiques ; Physical geography ; GB3-5030 ; Geography. Anthropology. Recreation ; G ; DOAJ:Geography ; DOAJ:Earth and Environmental Sciences
Language	French
Publishing date	2010-09-01T00:00:00Z
Publisher	Association pour la Diffusion de la Recherche Alpine
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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