Laboratoire d'optique et biosciences

Articles

  • Synthesis of acyclic nucleoside phosphonates targeting Flavin-Dependent Thymidylate Synthase in Mycobacterium tuberculosis
    • Biteau Nicolas G
    • Roy Vincent
    • Lambry J.-C.
    • Becker Hubert F
    • Myllykallio Hannu
    • Agrofoglio Luigi A
    Bioorganic and Medicinal Chemistry Letters, Elsevier , 2021, 46, pp.116351 . Flavin-Dependent Thymidylate Synthase (FDTS) encoded by ThyX gene was discovered as a new class of thymidylate synthase involved in the de novo synthesis of dTMP named only in 30 % of human pathogenic bacteria. This target was pursed for the development of new antibacterial agents against multiresistant pathogens. We have developed a new class of ANPs based on the mimic of two natural’s cofactors (dUMP and FAD) as inhibitors against Mycobacterium tuberculosis ThyX. Several synthetic efforts were performed to optimize regioselective N1-alkylation, cross-coupling metathesis and Sonogashira cross-coupling. Compound 19c showed a poor 31.8% inhibitory effect on ThyX at 200 μM. (10.1016/j.bmc.2021.116351)
    DOI : 10.1016/j.bmc.2021.116351
  • Methylselenol Produced In Vivo from Methylseleninic Acid or Dimethyl Diselenide Induces Toxic Protein Aggregation in Saccharomyces cerevisiae
    • Dauplais Marc
    • Bierla Katarzyna
    • Maizeray Coralie
    • Lestini Roxane
    • Lobinski Ryszard
    • Plateau Pierre
    • Szpunar Joanna
    • Lazard Myriam
    International Journal of Molecular Sciences, MDPI , 2021, 22 (5), pp.2241 . Methylselenol (MeSeH) has been suggested to be a critical metabolite for anticancer activity of selenium, although the mechanisms underlying its activity remain to be fully established. The aim of this study was to identify metabolic pathways of MeSeH in Saccharomyces cerevisiae to decipher the mechanism of its toxicity. We first investigated in vitro the formation of MeSeH from methylseleninic acid (MSeA) or dimethyldiselenide. Determination of the equilibrium and rate constants of the reactions between glutathione (GSH) and these MeSeH precursors indicates that in the conditions that prevail in vivo, GSH can reduce the major part of MSeA or dimethyldiselenide into MeSeH. MeSeH can also be enzymatically produced by glutathione reductase or thioredoxin/thioredoxin reductase. Studies on the toxicity of MeSeH precursors (MSeA, dimethyldiselenide or a mixture of MSeA and GSH) in S.cerevisiae revealed that cytotoxicity and selenomethionine content were severely reduced in a met17 mutant devoid of O-acetylhomoserine sulfhydrylase. This suggests conversion of MeSeH into selenomethionine by this enzyme. Protein aggregation was observed in wild-type but not in met17 cells. Altogether, our findings support the view that MeSeH is toxic in S. cerevisiae because it is metabolized into selenomethionine which, in turn, induces toxic protein aggregation. (10.3390/ijms22052241)
    DOI : 10.3390/ijms22052241
  • Simultaneous NAD(P)H and FAD fluorescence lifetime microscopy of long UVA–induced metabolic stress in reconstructed human skin
    • Ung Thi Phuong Lien
    • Lim Seongbin
    • Solinas Xavier
    • Mahou Pierre
    • Chessel Anatole
    • Marionnet Claire
    • Bornschlögl Thomas
    • Beaurepaire Emmanuel
    • Bernerd Françoise
    • Pena Ana-Maria
    • Stringari Chiara
    Scientific Reports, Nature Publishing Group , 2021, 11, pp.22171 . Solar ultraviolet longwave UVA1 exposure of human skin has short-term consequences at cellular and molecular level, leading at long-term to photoaging. Following exposure, reactive oxygen species (ROS) are generated, inducing oxidative stress that might impair cellular metabolic activity. However, the dynamic of UVA1 impact on cellular metabolism remains unknown because of lacking adequate live imaging techniques. Here we assess the UVA1-induced metabolic stress response in reconstructed human skin with multicolor two-photon fluorescence lifetime microscopy (FLIM). Simultaneous imaging of nicotinamide adenine dinucleotide (NAD(P)H) and flavin adenine dinucleotide (FAD) by wavelength mixing allows quantifying cellular metabolism in function of NAD(P) + /NAD(P)H and FAD/FADH 2 redox ratios. After UVA1 exposure, we observe an increase of fraction of bound NAD(P)H and decrease of fraction of bound FAD indicating a metabolic switch from glycolysis to oxidative phosphorylation or oxidative stress possibly correlated to ROS generation. NAD(P)H and FAD biomarkers have unique temporal dynamic and sensitivity to skin cell types and UVA1 dose. While the FAD biomarker is UVA1 dose-dependent in keratinocytes, the NAD(P)H biomarker shows no dose dependence in keratinocytes, but is directly affected after exposure in fibroblasts, thus reflecting different skin cells sensitivities to oxidative stress. Finally, we show that a sunscreen including a UVA1 filter prevents UVA1 metabolic stress response from occurring. (10.1038/s41598-021-00126-8)
    DOI : 10.1038/s41598-021-00126-8
  • Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
    • Klionsky Daniel
    • Abdel-Aziz Amal Kamal
    • Abdelfatah Sara
    • Abdellatif Mahmoud
    • Abdoli Asghar
    • Abel Steffen
    • Abeliovich Hagai
    • Abildgaard Marie
    • Abudu Yakubu Princely
    • Acevedo-Arozena Abraham
    • Adamopoulos Iannis
    • Adeli Khosrow
    • Adolph Timon
    • Adornetto Annagrazia
    • Aflaki Elma
    • Agam Galila
    • Agarwal Anupam
    • Aggarwal Bharat
    • Agnello Maria
    • Agostinis Patrizia
    • Agrewala Javed
    • Agrotis Alexander
    • Aguilar Patricia
    • Ahmad S. Tariq
    • Ahmed Zubair
    • Ahumada-Castro Ulises
    • Aits Sonja
    • Aizawa Shu
    • Akkoc Yunus
    • Akoumianaki Tonia
    • Akpinar Hafize Aysin
    • Al-Abd Ahmed
    • Al-Akra Lina
    • Al-Gharaibeh Abeer
    • Alaoui-Jamali Moulay
    • Alberti Simon
    • Alcocer-Gómez Elísabet
    • Alessandri Cristiano
    • Ali Muhammad
    • Alim Al-Bari M. Abdul
    • Aliwaini Saeb
    • Alizadeh Javad
    • Almacellas Eugènia
    • Almasan Alexandru
    • Alonso Alicia
    • Alonso Guillermo
    • Altan-Bonnet Nihal
    • Altieri Dario
    • Álvarez Élida
    • Alves Sara
    • Alves da Costa Cristine
    • Alzaharna Mazen
    • Amadio Marialaura
    • Amantini Consuelo
    • Amaral Cristina
    • Ambrosio Susanna
    • Amer Amal
    • Ammanathan Veena
    • An Zhenyi
    • Andersen Stig
    • Andrabi Shaida
    • Andrade-Silva Magaiver
    • Andres Allen
    • Angelini Sabrina
    • Ann David
    • Anozie Uche
    • Ansari Mohammad
    • Antas Pedro
    • Antebi Adam
    • Antón Zuriñe
    • Anwar Tahira
    • Apetoh Lionel
    • Apostolova Nadezda
    • Araki Toshiyuki
    • Araki Yasuhiro
    • Arasaki Kohei
    • Araújo Wagner
    • Araya Jun
    • Arden Catherine
    • Arévalo Maria-Angeles
    • Arguelles Sandro
    • Arias Esperanza
    • Arikkath Jyothi
    • Arimoto Hirokazu
    • Ariosa Aileen
    • Armstrong-James Darius
    • Arnauné-Pelloquin Laetitia
    • Aroca Angeles
    • Arroyo Daniela
    • Arsov Ivica
    • Artero Rubén
    • Asaro Dalia Maria Lucia
    • Aschner Michael
    • Ashrafizadeh Milad
    • Ashur-Fabian Osnat
    • Atanasov Atanas
    • Au Alicia
    • Auberger Patrick
    • Auner Holger
    • Aurelian Laure
    • Autelli Riccardo
    • Avagliano Laura
    • Ávalos Yenniffer
    • Aveic Sanja
    • Aveleira Célia Alexandra
    • Avin-Wittenberg Tamar
    • Aydin Yucel
    • Ayton Scott
    • Ayyadevara Srinivas
    • Azzopardi Maria
    • Baba Misuzu
    • Backer Jonathan
    • Backues Steven
    • Bae Dong-Hun
    • Bae Ok-Nam
    • Bae Soo Han
    • Baehrecke Eric
    • Baek Ahruem
    • Baek Seung-Hoon
    • Baek Sung Hee
    • Bagetta Giacinto
    • Bagniewska-Zadworna Agnieszka
    • Bai Hua
    • Bai Jie
    • Bai Xiyuan
    • Bai Yidong
    • Bairagi Nandadulal
    • Baksi Shounak
    • Balbi Teresa
    • Baldari Cosima
    • Balduini Walter
    • Ballabio Andrea
    • Ballester Maria
    • Balazadeh Salma
    • Balzan Rena
    • Bandopadhyay Rina
    • Banerjee Sreeparna
    • Banerjee Sulagna
    • Bánréti Ágnes
    • Bao Yan
    • Baptista Mauricio
    • Baracca Alessandra
    • Barbati Cristiana
    • Bargiela Ariadna
    • Barilà Daniela
    • Barlow Peter
    • Barmada Sami
    • Barreiro Esther
    • Barreto George
    • Bartek Jiri
    • Bartel Bonnie
    • Bartolome Alberto
    • Barve Gaurav
    • Basagoudanavar Suresh
    • Bassham Diane
    • Bast Robert
    • Basu Alakananda
    • Batoko Henri
    • Batten Isabella
    • Baulieu Etienne
    • Baumgarner Bradley
    • Bayry Jagadeesh
    • Beale Rupert
    • Beau Isabelle
    • Beaumatin Florian
    • Bechara Luiz R.G.
    • Beck George
    • Beers Michael
    • Begun Jakob
    • Behrends Christian
    • Behrens Georg M.N.
    • Bei Roberto
    • Bejarano Eloy
    • Bel Shai
    • Behl Christian
    • Belaid Amine
    • Belgareh-Touzé Naïma
    • Bellarosa Cristina
    • Belleudi Francesca
    • Belló Pérez Melissa
    • Bello-Morales Raquel
    • Beltran Jackeline Soares de Oliveira
    • Beltran Sebastián
    • Benbrook Doris Mangiaracina
    • Bendorius Mykolas
    • Benitez Bruno
    • Benito-Cuesta Irene
    • Bensalem Julien
    • Berchtold Martin
    • Berezowska Sabina
    • Bergamaschi Daniele
    • Bergami Matteo
    • Bergmann Andreas
    • Berliocchi Laura
    • Berlioz-Torrent Clarisse
    • Bernard Amélie
    • Berthoux Lionel
    • Besirli Cagri
    • Besteiro Sébastien
    • Betin Virginie
    • Beyaert Rudi
    • Bezbradica Jelena
    • Bhaskar Kiran
    • Bhatia-Kissova Ingrid
    • Bhattacharya Resham
    • Bhattacharya Sujoy
    • Bhattacharyya Shalmoli
    • Bhuiyan Md. Shenuarin
    • Bhutia Sujit Kumar
    • Bi Lanrong
    • Bi Xiaolin
    • Biden Trevor
    • Bijian Krikor
    • Billes Viktor
    • Binart Nadine
    • Bincoletto Claudia
    • Birgisdottir Asa
    • Bjorkoy Geir
    • Blanco Gonzalo
    • Blas-Garcia Ana
    • Blasiak Janusz
    • Blomgran Robert
    • Blomgren Klas
    • Blum Janice
    • Boada-Romero Emilio
    • Boban Mirta
    • Boesze-Battaglia Kathleen
    • Boeuf Philippe
    • Boland Barry
    • Bomont Pascale
    • Bonaldo Paolo
    • Bonam Srinivasa Reddy
    • Bonfili Laura
    • Bonifacino Juan
    • Boone Brian
    • Bootman Martin
    • Bordi Matteo
    • Borner Christoph
    • Bornhauser Beat
    • Borthakur Gautam
    • Bosch Jürgen
    • Bose Santanu
    • Botana Luis
    • Botas Juan
    • Boulanger Chantal
    • Boulton Michael
    • Bourdenx Mathieu
    • Bourgeois Benjamin
    • Bourke Nollaig
    • Bousquet Guilhem
    • Boya Patricia
    • Bozhkov Peter
    • Bozi Luiz
    • Bozkurt Tolga
    • Brackney Doug
    • Brandts Christian
    • Braun Ralf
    • Braus Gerhard
    • Bravo-Sagua Roberto
    • Bravo-San Pedro José M.
    • Brest Patrick
    • Bringer Marie-Agnès
    • Briones-Herrera Alfredo
    • Broaddus V. Courtney
    • Brodersen Peter
    • Brodsky Jeffrey
    • Brody Steven
    • Bronson Paola
    • Bronstein Jeff
    • Brown Carolyn
    • Brown Rhoderick
    • Brum Patricia
    • Brumell John
    • Brunetti-Pierri Nicola
    • Bruno Daniele
    • Bryson-Richardson Robert
    • Bucci Cecilia
    • Buchrieser Carmen
    • Bueno Marta
    • Buitrago-Molina Laura Elisa
    • Buraschi Simone
    • Buch Shilpa
    • Buchan J. Ross
    • Buckingham Erin
    • Budak Hikmet
    • Budini Mauricio
    • Bultynck Geert
    • Burada Florin
    • Burgoyne Joseph
    • Burón M. Isabel
    • Bustos Victor
    • Büttner Sabrina
    • Butturini Elena
    • Byrd Aaron
    • Cabas Isabel
    • Cabrera-Benitez Sandra
    • Cadwell Ken
    • Cai Jingjing
    • Cai Lu
    • Cai Qian
    • Cairó Montserrat
    • Calbet Jose
    • Caldwell Guy
    • Caldwell Kim
    • Call Jarrod
    • Calvani Riccardo
    • Calvo Ana
    • Calvo-Rubio Barrera Miguel
    • Camara Niels Os
    • Camonis Jacques H.
    • Camougrand Nadine
    • Campanella Michelangelo
    • Campbell Edward
    • Campbell-Valois François-Xavier
    • Campello Silvia
    • Campesi Ilaria
    • Campos Juliane
    • Camuzard Olivier
    • Cancino Jorge
    • Candido de Almeida Danilo
    • Canesi Laura
    • Caniggia Isabella
    • Canonico Barbara
    • Cantí Carles
    • Cao Bin
    • Caraglia Michele
    • Caramés Beatriz
    • Carchman Evie
    • Cardenal-Muñoz Elena
    • Cardenas Cesar
    • Cardenas Luis
    • Cardoso Sandra
    • Carew Jennifer
    • Carle Georges F.
    • Carleton Gillian
    • Carloni Silvia
    • Carmona-Gutierrez Didac
    • Carneiro Leticia
    • Carnevali Oliana
    • Carosi Julian
    • Carra Serena
    • Carrier Alice
    • Carrier Lucie
    • Carroll Bernadette
    • Carter A. Brent
    • Carvalho Andreia Neves
    • Casanova Magali
    • Casas Caty
    • Casas Josefina
    • Cassioli Chiara
    • Castillo Eliseo
    • Castillo Karen
    • Castillo-Lluva Sonia
    • Castoldi Francesca
    • Castori Marco
    • Castro Ariel
    • Castro-Caldas Margarida
    • Castro-Hernandez Javier
    • Castro-Obregon Susana
    • Catz Sergio
    • Cavadas Claudia
    • Cavaliere Federica
    • Cavallini Gabriella
    • Cavinato Maria
    • Cayuela Maria
    • Cebollada Rica Paula
    • Cecarini Valentina
    • Cecconi Francesco
    • Cechowska-Pasko Marzanna
    • Cenci Simone
    • Ceperuelo-Mallafré Victòria
    • Cerqueira João
    • Cerutti Janete
    • Cervia Davide
    • Cetintas Vildan Bozok
    • Cetrullo Silvia
    • Chae Han-Jung
    • Chagin Andrei
    • Chai Chee-Yin
    • Chakrabarti Gopal
    • Chakrabarti Oishee
    • Chakraborty Tapas
    • Chakraborty Trinad
    • Chami Mounia
    • Chamilos Georgios
    • Chan David
    • Chan Edmond
    • Chan Edward
    • Chan H.Y. Edwin
    • Chan Helen
    • Chan Hung
    • Chan Matthew T.V.
    • Chan Yau Sang
    • Chandra Partha
    • Chang Chih-Peng
    • Chang Chunmei
    • Chang Hao-Chun
    • Chang Kai
    • Chao Jie
    • Chapman Tracey
    • Charlet-Berguerand Nicolas
    • Chatterjee Samrat
    • Chaube Shail
    • Chaudhary Anu
    • Chauhan Santosh
    • Chaum Edward
    • Checler Frédéric
    • Cheetham Michael
    • Chen Chang-Shi
    • Chen Guang-Chao
    • Chen Jian-Fu
    • Chen Liam
    • Chen Leilei
    • Chen Lin
    • Chen Mingliang
    • Chen Mu-Kuan
    • Chen Ning
    • Chen Quan
    • Chen Ruey-Hwa
    • Chen Shi
    • Chen Wei
    • Chen Weiqiang
    • Chen Xin-Ming
    • Chen Xiong-Wen
    • Chen Xu
    • Chen Yan
    • Chen Ye-Guang
    • Chen Yingyu
    • Chen Yongqiang
    • Chen Yu-Jen
    • Chen Yue-Qin
    • Chen Zhefan Stephen
    • Chen Zhi
    • Chen Zhi-Hua
    • Chen Zhijian
    • Chen Zhixiang
    • Cheng Hanhua
    • Cheng Jun
    • Cheng Shi-Yuan
    • Cheng Wei
    • Cheng Xiaodong
    • Cheng Xiu-Tang
    • Cheng Yiyun
    • Cheng Zhiyong
    • Chen Zhong
    • Cheong Heesun
    • Cheong Jit Kong
    • Chernyak Boris
    • Cherry Sara
    • Cheung Chi Fai Randy
    • Cheung Chun Hei Antonio
    • Cheung King-Ho
    • Chevet Eric
    • Chi Richard
    • Chiang Alan Kwok Shing
    • Chiaradonna Ferdinando
    • Chiarelli Roberto
    • Chiariello Mario
    • Chica Nathalia
    • Chiocca Susanna
    • Chiong Mario
    • Chiou Shih-Hwa
    • Chiramel Abhilash
    • Chiurchiù Valerio
    • Cho Dong-Hyung
    • Choe Seong-Kyu
    • Choi Augustine M.K.
    • Choi Mary
    • Choudhury Kamalika Roy
    • Chow Norman
    • Chu Charleen
    • Chua Jason
    • Chua John Jia En
    • Chung Hyewon
    • Chung Kin Pan
    • Chung Seockhoon
    • Chung So-Hyang
    • Chung Yuen-Li
    • Cianfanelli Valentina
    • Ciechomska Iwona
    • Cifuentes Mariana
    • Cinque Laura
    • Cirak Sebahattin
    • Cirone Mara
    • Clague Michael
    • Clarke Robert
    • Clementi Emilio
    • Coccia Eliana
    • Codogno Patrice
    • Cohen Ehud
    • Cohen Mickael M.
    • Colasanti Tania
    • Colasuonno Fiorella
    • Colbert Robert
    • Colell Anna
    • Čolić Miodrag
    • Coll Nuria
    • Collins Mark
    • Colombo María
    • Colón-Ramos Daniel
    • Combaret Lydie
    • Comincini Sergio
    • Cominetti Márcia
    • Consiglio Antonella
    • Conte Andrea
    • Conti Fabrizio
    • Contu Viorica Raluca
    • Cookson Mark
    • Coombs Kevin
    • Coppens Isabelle
    • Corasaniti Maria Tiziana
    • Corkery Dale
    • Cordes Nils
    • Cortese Katia
    • Costa Maria Do Carmo
    • Costantino Sarah
    • Costelli Paola
    • Coto-Montes Ana
    • Crack Peter
    • Crespo Jose
    • Criollo Alfredo
    • Crippa Valeria
    • Cristofani Riccardo
    • Csizmadia Tamas
    • Cuadrado Antonio
    • Cui Bing
    • Cui Jun
    • Cui Yixian
    • Cui Yong
    • Culetto Emmanuel
    • Cumino Andrea
    • Cybulsky Andrey
    • Czaja Mark
    • Czuczwar Stanislaw
    • D’adamo Stefania
    • D’amelio Marcello
    • D’arcangelo Daniela
    • D’lugos Andrew
    • D’orazi Gabriella
    • da Silva James
    • Dafsari Hormos Salimi
    • Dagda Ruben
    • Dagdas Yasin
    • Daglia Maria
    • Dai Xiaoxia
    • Dai Yun
    • Dai Yuyuan
    • Dal Col Jessica
    • Dalhaimer Paul
    • Dalla Valle Luisa
    • Dallenga Tobias
    • Dalmasso Guillaume
    • Damme Markus
    • Dando Ilaria
    • Dantuma Nico
    • Darling April
    • Das Hiranmoy
    • Dasarathy Srinivasan
    • Dasari Santosh
    • Dash Srikanta
    • Daumke Oliver
    • Dauphinee Adrian
    • Davies Jeffrey
    • Dávila Valeria
    • Davis Roger
    • Davis Tanja
    • Dayalan Naidu Sharadha
    • de Amicis Francesca
    • de Bosscher Karolien
    • de Felice Francesca
    • de Franceschi Lucia
    • de Leonibus Chiara
    • de Mattos Barbosa Mayara
    • de Meyer Guido R.Y.
    • de Milito Angelo
    • de Nunzio Cosimo
    • de Palma Clara
    • de Santi Mauro
    • de Virgilio Claudio
    • de Zio Daniela
    • Debnath Jayanta
    • Debosch Brian
    • Decuypere Jean-Paul
    • Deehan Mark
    • Deflorian Gianluca
    • Degregori James
    • Dehay Benjamin
    • del Rio Gabriel
    • Delaney Joe
    • Delbridge Lea
    • Delorme-Axford Elizabeth
    • Delpino M. Victoria
    • Demarchi Francesca
    • Dembitz Vilma
    • Demers Nicholas
    • Deng Hongbin
    • Deng Zhiqiang
    • Dengjel Joern
    • Dent Paul
    • Denton Donna
    • Depamphilis Melvin
    • Der Channing
    • Deretic Vojo
    • Descoteaux Albert
    • Devis Laura
    • Devkota Sushil
    • Devuyst Olivier
    • Dewson Grant
    • Dharmasivam Mahendiran
    • Dhiman Rohan
    • Di Bernardo Diego
    • Di Cristina Manlio
    • Di Domenico Fabio
    • Di Fazio Pietro
    • Di Fonzo Alessio
    • Di Guardo Giovanni
    • Di Guglielmo Gianni
    • Di Leo Luca
    • Di Malta Chiara
    • Di Nardo Alessia
    • Di Rienzo Martina
    • Di Sano Federica
    • Diallinas George
    • Diao Jiajie
    • Diaz-Araya Guillermo
    • Díaz-Laviada Inés
    • Dickinson Jared
    • Diederich Marc
    • Dieudé Mélanie
    • Dikic Ivan
    • Ding Shiping
    • Ding Wen-Xing
    • Dini Luciana
    • Dinić Jelena
    • Dinic Miroslav
    • Dinkova-Kostova Albena
    • Dionne Marc
    • Distler Jörg H.W.
    • Diwan Abhinav
    • Dixon Ian M.C.
    • Djavaheri-Mergny Mojgan
    • Dobrinski Ina
    • Dobrovinskaya Oxana
    • Dobrowolski Radek
    • Dobson Renwick C.J.
    • Đokić Jelena
    • Dokmeci Emre Serap
    • Donadelli Massimo
    • Dong Bo
    • Dong Xiaonan
    • Dong Zhiwu
    • 2nd Dorn Gerald
    • Dotsch Volker
    • Dou Huan
    • Dou Juan
    • Dowaidar Moataz
    • Dridi Sami
    • Drucker Liat
    • Du Ailian
    • Du Caigan
    • Du Guangwei
    • Du Hai-Ning
    • Du Li-Lin
    • Du Toit André
    • Duan Shao-Bin
    • Duan Xiaoqiong
    • Duarte Sónia
    • Dubrovska Anna
    • Dunlop Elaine
    • Dupont Nicolas
    • Durán Raúl
    • Dwarakanath Bilikere
    • Dyshlovoy Sergey
    • Ebrahimi-Fakhari Darius
    • Eckhart Leopold
    • Edelstein Charles
    • Efferth Thomas
    • Eftekharpour Eftekhar
    • Eichinger Ludwig
    • Eid Nabil
    • Eisenberg Tobias
    • Eissa N. Tony
    • Eissa Sanaa
    • Ejarque Miriam
    • El Andaloussi Abdeljabar
    • El-Hage Nazira
    • El-Naggar Shahenda
    • Eleuteri Anna Maria
    • El-Shafey Eman
    • Elgendy Mohamed
    • Eliopoulos Aristides
    • Elizalde María
    • Elks Philip
    • Elsasser Hans-Peter
    • Elsherbiny Eslam
    • Emerling Brooke
    • Emre N.
    • Eng Christina
    • Engedal Nikolai
    • Engelbrecht Anna-Mart
    • Engelsen Agnete S.T.
    • Enserink Jorrit
    • Escalante Ricardo
    • Esclatine Audrey
    • Escobar-Henriques Mafalda
    • Eskelinen Eeva-Liisa
    • Espert Lucile
    • Eusebio Makandjou-Ola
    • Fabrias Gemma
    • Fabrizi Cinzia
    • Facchiano Antonio
    • Facchiano Francesco
    • Fadeel Bengt
    • Fader Claudio
    • Faesen Alex
    • Fairlie W. Douglas
    • Falcó Alberto
    • Falkenburger Bjorn
    • Fan Daping
    • Fan Jie
    • Fan Yanbo
    • Fang Evandro
    • Fang Yanshan
    • Fang Yognqi
    • Fanto Manolis
    • Farfel-Becker Tamar
    • Faure Mathias
    • Fazeli Gholamreza
    • Fedele Anthony
    • Feldman Arthur
    • Feng Du
    • Feng Jiachun
    • Feng Lifeng
    • Feng Yibin
    • Feng Yuchen
    • Feng Wei
    • Fenz Araujo Thais
    • Ferguson Thomas
    • Fernández Álvaro
    • Fernandez-Checa Jose
    • Fernández-Veledo Sonia
    • Fernie Alisdair
    • Ferrante Anthony
    • Ferraresi Alessandra
    • Ferrari Merari
    • Ferreira Julio C.B.
    • Ferro-Novick Susan
    • Figueras Antonio
    • Filadi Riccardo
    • Filigheddu Nicoletta
    • Filippi-Chiela Eduardo
    • Filomeni Giuseppe
    • Fimia Gian Maria
    • Fineschi Vittorio
    • Finetti Francesca
    • Finkbeiner Steven
    • Fisher Edward
    • Fisher Paul
    • Flamigni Flavio
    • Fliesler Steven
    • Flo Trude
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    • Voos Wolfgang
    • Vucicevic Ljubica
    • Wade-Martins Richard
    • Waguri Satoshi
    • A. Waite Kenrick
    • Wakatsuki Shuji
    • W. Walker David
    • J. Walker Mark
    • A. Walker Simon
    • Walter Jochen
    • G. Wandosell Francisco
    • Wang Bo
    • Wang Chao-Yung
    • Wang Chen
    • Wang Chenran
    • Wang Chenwei
    • Wang Cun-Yu
    • Wang Dong
    • Wang Fangyang
    • Wang Feng
    • Wang Fengming
    • Wang Guansong
    • Wang Han
    • Wang Hao
    • Wang Hexiang
    • Wang Hong-Gang
    • Wang Jianrong
    • Wang Jigang
    • Wang Jiou
    • Wang Jundong
    • Wang Kui
    • Wang Lianrong
    • Wang Liming
    • Haitian Wang Maggie
    • Wang Meiqing
    • Wang Nanbu
    • Wang Pengwei
    • Wang Peipei
    • Wang Ping
    • Wang Ping
    • Jun Wang Qing
    • Wang Qing
    • Kenneth Wang Qing
    • A. Wang Qiong
    • Wang Wen-Tao
    • Wang Wuyang
    • Wang Xinnan
    • Wang Xuejun
    • Wang Yan
    • Wang Yanchang
    • Wang Yanzhuang
    • Wang Yen-Yun
    • Wang Yihua
    • Wang Yipeng
    • Wang Yu
    • Wang Yuqi
    • Wang Zhe
    • Wang Zhenyu
    • Wang Zhouguang
    • Warnes Gary
    • Warnsmann Verena
    • Watada Hirotaka
    • Watanabe Eizo
    • Watchon Maxinne
    • Wawrzyńska Anna
    • E. Weaver Timothy
    • Wegrzyn Grzegorz
    • M. Wehman Ann
    • Wei Huafeng
    • Wei Lei
    • Wei Taotao
    • Wei Yongjie
    • H. Weiergräber Oliver
    • C. Weihl Conrad
    • Weindl Günther
    • Weiskirchen Ralf
    • Wells Alan
    • H. Wen Runxia
    • Wen Xin
    • Werner Antonia
    • Weykopf Beatrice
    • P. Wheatley Sally
    • Lindsay Whitton J.
    • J. Whitworth Alexander
    • Wiktorska Katarzyna
    • E. Wildenberg Manon
    • Wileman Tom
    • Wilkinson Simon
    • Willbold Dieter
    • Williams Brett
    • S. B. Williams Robin
    • L. Williams Roger
    • R. Williamson Peter
    • A. Wilson Richard
    • Winner Beate
    • J. Winsor Nathaniel
    • S. Witkin Steven
    • Wodrich Harald
    • Woehlbier Ute
    • Wollert Thomas
    • Wong Esther
    • Ho Wong Jack
    • W. Wong Richard
    • Kam Wai Wong Vincent
    • Wei-Lynn Wong W.
    • Wu An-Guo
    • Wu Chengbiao
    • Wu Jian
    • Wu Junfang
    • K. Wu Kenneth
    • Wu Min
    • Wu Shan-Ying
    • Wu Shengzhou
    • Wu Shu-Yan
    • Wu Shufang
    • K.K. Wu William
    • Wu Xiaohong
    • Wu Xiaoqing
    • Wu Yao-Wen
    • Wu Yihua
    • J. Xavier Ramnik
    • Xia Hongguang
    • Xia Lixin
    • Xia Zhengyuan
    • Xiang Ge
    • Xiang Jin
    • Xiang Mingliang
    • Xiang Wei
    • Xiao Bin
    • Xiao Guozhi
    • Xiao Hengyi
    • Xiao Hong-Tao
    • Xiao Jian
    • Xiao Lan
    • Xiao Shi
    • Xiao Yin
    • Xie Baoming
    • Xie Chuan-Ming
    • Xie Min
    • Xie Yuxiang
    • Xie Zhiping
    • Xie Zhonglin
    • Xilouri Maria
    • Xu Congfeng
    • Xu En
    • Xu Haoxing
    • Xu Jing
    • Xu Jinrong
    • Xu Liang
    • Wen Xu Wen
    • Xu Xiulong
    • Xue Yu
    • M.S. Yakhine-Diop Sokhna
    • Yamaguchi Masamitsu
    • Yamaguchi Osamu
    • Yamamoto Ai
    • Yamashina Shunhei
    • Yan Shengmin
    • Yan Shian-Jang
    • Yan Zhen
    • Yanagi Yasuo
    • Yang Chuanbin
    • Yang Dun-Sheng
    • Yang Huan
    • Yang Huang-Tian
    • Yang Hui
    • Yang Jin-Ming
    • Yang Jing
    • Yang Jingyu
    • Yang Ling
    • Yang Liu
    • Yang Ming
    • Yang Pei-Ming
    • Yang Qian
    • Yang Seungwon
    • Yang Shu
    • Yang Shun-Fa
    • Yang Wannian
    • Yuan Yang Wei
    • Yang Xiaoyong
    • Yang Xuesong
    • Yang Yi
    • Yang Ying
    • Yao Honghong
    • Yao Shenggen
    • Yao Xiaoqiang
    • Yao Yong-Gang
    • Yao Yong-Ming
    • Yasui Takahiro
    • Yazdankhah Meysam
    • M. Yen Paul
    • Yi Cong
    • Yin Xiao-Ming
    • Yin Yanhai
    • Yin Zhangyuan
    • Yin Ziyi
    • Ying Meidan
    • Ying Zheng
    • K. Yip Calvin
    • Pei Tung Yiu Stephanie
    • H. Yoo Young
    • Yoshida Kiyotsugu
    • R. Yoshii Saori
    • Yoshimori Tamotsu
    • Yousefi Bahman
    • Yu Boxuan
    • Yu Haiyang
    • Yu Jun
    • Yu Jun
    • Yu Li
    • Yu Ming-Lung
    • Yu Seong-Woon
    • C. Yu Victor
    • Haung Yu W.
    • Yu Zhengping
    • Yu Zhou
    • Yuan Junying
    • Yuan Ling-Qing
    • Yuan Shilin
    • F. Yuan Shyng-Shiou
    • Yuan Yanggang
    • Yuan Zengqiang
    • Yue Jianbo
    • Yue Zhenyu
    • Yun Jeanho
    • L. Yung Raymond
    • N. Zacks David
    • Zaffagnini Gabriele
    • O. Zambelli Vanessa
    • Zanella Isabella
    • S. Zang Qun
    • Zanivan Sara
    • Zappavigna Silvia
    • Zaragoza Pilar
    • S. Zarbalis Konstantinos
    • Zarebkohan Amir
    • Zarrouk Amira
    • O. Zeitlin Scott
    • Zeng Jialiu
    • Zeng Ju-Deng
    • Žerovnik Eva
    • Zhan Lixuan
    • Zhang Bin
    • D. Zhang Donna
    • Zhang Hanlin
    • Zhang Hong
    • Zhang Hong
    • Zhang Honghe
    • Zhang Huafeng
    • Zhang Huaye
    • Zhang Hui
    • Zhang Hui-Ling
    • Zhang Jianbin
    • Zhang Jianhua
    • Zhang Jing-Pu
    • Y.B. Zhang Kalin
    • W. Zhang Leshuai
    • Zhang Lin
    • Zhang Lisheng
    • Zhang Lu
    • Zhang Luoying
    • Zhang Menghuan
    • Zhang Peng
    • Zhang Sheng
    • Zhang Wei
    • Zhang Xiangnan
    • Zhang Xiao-Wei
    • Zhang Xiaolei
    • Zhang Xiaoyan
    • Zhang Xin
    • Zhang Xinxin
    • Dong Zhang Xu
    • Zhang Yang
    • Zhang Yanjin
    • Zhang Yi
    • Zhang Ying-Dong
    • Zhang Yingmei
    • Zhang Yuan-Yuan
    • Zhang Yuchen
    • Zhang Zhe
    • Zhang Zhengguang
    • Zhang Zhibing
    • Zhang Zhihai
    • Zhang Zhiyong
    • Zhang Zili
    • Zhao Haobin
    • Zhao Lei
    • Zhao Shuang
    • Zhao Tongbiao
    • Zhao Xiao-Fan
    • Zhao Ying
    • Zhao Yongchao
    • Zhao Yongliang
    • Zhao Yuting
    • Zheng Guoping
    • Zheng Kai
    • Zheng Ling
    • Zheng Shizhong
    • Zheng Xi-Long
    • Zheng Yi
    • Zheng Zu-Guo
    • Zhivotovsky Boris
    • Zhong Qing
    • Zhou Ao
    • Zhou Ben
    • Zhou Cefan
    • Zhou Gang
    • Zhou Hao
    • Zhou Hongbo
    • Zhou Jie
    • Zhou Jing
    • Zhou Jing
    • Zhou Jiyong
    • Zhou Kailiang
    • Zhou Rongjia
    • Zhou Xu-Jie
    • Zhou Yanshuang
    • Zhou Yinghong
    • Zhou Yubin
    • Zhou Zheng-Yu
    • Zhou Zhou
    • Zhu Binglin
    • Zhu Changlian
    • Zhu Guo-Qing
    • Zhu Haining
    • Zhu Hongxin
    • Zhu Hua
    • Zhu Wei-Guo
    • Zhu Yanping
    • Zhu Yushan
    • Zhuang Haixia
    • Zhuang Xiaohong
    • Zientara-Rytter Katarzyna
    • M. Zimmermann Christine
    • Ziviani Elena
    • Zoladek Teresa
    • Zong Wei-Xing
    • B. Zorov Dmitry
    • Zorzano Antonio
    • Zou Weiping
    • Zou Zhen
    • Zou Zhengzhi
    • Zuryn Steven
    • Zwerschke Werner
    • Brand-Saberi Beate
    • Charlie Dong X.
    • Shekar Kenchappa Chandra
    • Li Zuguo
    • Lin Yong
    • Oshima Shigeru
    • Rong Yueguang
    • C. Sluimer Judith
    • L. Stallings Christina
    • Tong Chun-Kit
    Autophagy, Taylor & Francis , 2021, 17 (1), pp.1-382 . In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field. (10.1080/15548627.2020.1797280)
    DOI : 10.1080/15548627.2020.1797280
  • Mechanism of Naphthoquinone Selectivity of Thymidylate Synthase ThyX
    • Myllykallio Hannu
    • Becker Hubert F
    • Aleksandrov Alexey
    Biophysical Journal, Biophysical Society , 2020, 119 (12), pp.2508-2516 . Naphthoquinones (NQs) are natural and synthetic compounds with a wide range of biological activities commonly attributed to their redox activity and/or chemical reactivity. However, genetic and biochemical experiments have recently demonstrated that 2-hydroxy-NQs (2-OH-NQs) act as highly specific non-covalent inhibitors of the essential bacterial thymidylate synthase ThyX in a cellular context. We used biochemical experiments and molecular dynamics simulations to elucidate the selective inhibition mechanism of NQ inhibitors of ThyX from Mycobacterium tuberculosis (Mtb). Free energy simulations rationalized how ThyX recognizes the natural substrate dUMP in the N3 ionized form using an arginine, Arg199 in Mtb. The results further demonstrated that 2-OH-NQ, similarly to dUMP, binds to ThyX in the ionized form and the strong and selective binding of 2-OH-NQ to ThyX is also explained by electrostatic interactions with Arg199. The stronger binding of the close analog 5F-dUMP to ThyX and its inhibitory properties compared to dUMP were explained by the stronger acidity of the uracil N3 atom. Our results, therefore, revealed that the ionization of 2-OH-NQs drives their biological activities by mimicking the interactions with the natural substrate. Our observations encourage the rational design of optimized ThyX inhibitors that ultimately may serve as antibiotics. (10.1016/j.bpj.2020.10.042)
    DOI : 10.1016/j.bpj.2020.10.042
  • Electric field measurements in plasmas: how focusing strongly distorts the E-FISH signal
    • Chng Tat Loon
    • Starikovskaia Svetlana
    • Schanne-Klein Marie-Claire
    Plasma Sources Science and Technology, IOP Publishing , 2020, 29 (12), pp.125002 . (10.1088/1361-6595/abbf93)
    DOI : 10.1088/1361-6595/abbf93
  • Télomères et Télomérase : des cibles toujours pertinentes en oncologie ?
    • Mergny Jean‐louis
    • Guittat Lionel
    • Ségal-Bendirdjian Évelyne
    Bulletin du Cancer, Elsevier , 2020, 108, pp.30-54 . (10.1016/j.bulcan.2020.10.007)
    DOI : 10.1016/j.bulcan.2020.10.007
  • Circular dichroism second-harmonic generation microscopy probes the polarity distribution of collagen fibrils
    • Schmeltz Margaux
    • Teulon Claire
    • Pinsard Maxime
    • Hansen Uwe
    • Alnawaiseh Maged
    • Ghoubay Djida
    • Borderie Vincent
    • Mosser Gervaise
    • Aimé Carole
    • Légaré François
    • Latour Gael
    • Schanne-Klein Marie-Claire
    Optica, Optical Society of America - OSA Publishing , 2020, 7 . Second-harmonic generation (SHG) microscopy is currently the preferred technique for visualizing collagen in intact tissues, but the usual implementations struggle to reveal collagen fibrils oriented out of the imaging plane. Recently, an advanced SHG modality, circular dichroism SHG (CD-SHG), has been proposed to specifically highlight out-of-plane fibrils. In this study, we present a theoretical analysis of CD-SHG signals that goes beyond the electric dipolar approximation to account for collagen chirality. We demonstrate that magnetic dipolar contributions are necessary to analyze CD-SHG images of human cornea sections and other collagen-rich samples. We show that the sign of CD-SHG signals does not reveal whether collagen fibrils point upwards or downwards as tentatively proposed previously. CD-SHG instead probes the polarity distribution of out-of-plane fibril assemblies at submicrometer scale, namely homogeneous polarity versus a mix of antiparallel fibrils. This makes CD-SHG a powerful tool for characterizing collagen organization in tissues, specifically the degree of disorder, which is affected during pathological remodeling. CD-SHG may thus serve to discriminate healthy and diseased collagen-rich tissues. (10.1364/optica.399246)
    DOI : 10.1364/optica.399246
  • Going Platinum to the Tune of a Remarkable Guanine Quadruplex Binder: Solution‐ and Solid‐State Investigations.
    • Miron Caitlin
    • van Staalduinen Laura
    • Rangaswamy Alana
    • Chen Mickey
    • Liang Yushi
    • Jia Zongchao
    • Mergny Jean‐louis
    • Petitjean Anne
    Angewandte Chemie International Edition, Wiley-VCH Verlag , 2020, pp.Online ahead of print . Guanine quadruplex recognition has gained increasing attention, inspired by the growing awareness of the key roles played by these non-canonical nucleic acid architectures in cellular regulatory processes. We report here the solution and solid-state studies of a novel planar platinum(II) complex that is easily assembled from a simple ligand, and exhibits notable binding affinity for guanine quadruplex structures, while maintaining good selectivity for guanine quadruplex over duplex structures. A crystal structure of this ligand complexed with a telomeric quadruplex confirms double end-capping, with dimerization at the 5' interface. (10.1002/anie.202012520)
    DOI : 10.1002/anie.202012520
  • Human papillomavirus G-rich regions as potential antiviral drug 1 targets
    • Carvalho Josué
    • Lopes-Nunes Jéssica
    • Campello Maria P C
    • Paulo António
    • Milici Janice
    • Meyers Craig
    • Mergny Jean‐louis
    • Salgado Gilmar F
    • Queiroz João A
    • Cruz Carla
    Nucleic Acid Therapeutics, Mary Ann Liebert, Inc. publishers , 2020 . Herein we report for the first time the screening of several ligands in terms of their ability to bind and stabilize G-quadruplexes found in seven human Papillomavirus (HPV) genomes. Using a variety of biophysical assays, HPV G-quadruplexes were shown to possess a high degree of structural polymorphism upon ligand binding which may have an impact on transcription, replication and viral protein production. A sequence found in high-risk HPV16 genotype folds into multiple non-canonical DNA structures; it was converted into a major G-quadruplex conformation upon interaction with a well-characterized highly selective G4-ligand, PhenDC3, which may have animpact on the viral infection. Likewise, HPV57 and 58, which fold into multiple G-quadruplex structures, were found to form single stable complexes in the presence of two other G4-ligands, C8and Pyridostatin, respectively. Additionally, one of the selected compounds, the acridine derivative C8, demonstrated a significant antiviral effect in HPV18-infected organotypic raft cultures. Altogether, these results indicate that targeting HPV G-quadruplexes may be an alternative route for the development of novel antiviral therapies.
  • Fast in vivo multiphoton light-sheet microscopy with optimal pulse frequency
    • Maioli Vincent
    • Boniface Antoine
    • Mahou Pierre
    • Ortas Júlia Ferrer
    • Abdeladim Lamiae
    • Beaurepaire Emmanuel
    • Supatto Willy
    Biomedical optics express, Optical Society of America - OSA Publishing , 2020, 11 (10), pp.6012-6026 . Improving the imaging speed of multiphoton microscopy is an active research field. Among recent strategies, light-sheet illumination holds distinctive advantages for achieving fast imaging in vivo. However, photoperturbation in multiphoton light-sheet microscopy remains poorly investigated. We show here that the heart beat rate of zebrafish embryos is a sensitive probe of linear and nonlinear photoperturbations. By analyzing its behavior with respect to laser power, pulse frequency and wavelength, we derive guidelines to find the best balance between signal and photoperturbation. We then demonstrate one order-of-magnitude signal enhancement over previous implementations by optimizing the laser pulse frequency. These results open new opportunities for fast live tissue imaging. (10.1364/BOE.400113)
    DOI : 10.1364/BOE.400113
  • Rôle pathogénique de l’expression anormale de la tétraspanine CD9 par les cellules épithéliales pariétales dans les glomérulopathies extracapillaires
    • Lazareth Hélène
    • Lenoir Olivia
    • Hénique Carole
    • Bouzigues Cédric
    • Boucheix Claude
    • Tharaux Pierre-Louis
    Médecine/Sciences, EDP Sciences , 2020, 36 (10), pp.852-855 . No abstract available (10.1051/medsci/2020154)
    DOI : 10.1051/medsci/2020154
  • G-Quadruplexes in the Archaea Domain
    • Brázda Václav
    • Luo Yu
    • Bartas Martin
    • Kaura Patrik
    • Porubiaková Otilia
    • Šťastný Jiří
    • Pečinka Petr
    • Verga Daniela
    • da Cunha Violette
    • Takahashi Tomio S
    • Forterre Patrick
    • Myllykallio Hannu
    • Fojta Miroslav
    • Mergny Jean‐louis
    Biomolecules, MDPI , 2020, 10 (9), pp.E1349 . The importance of unusual DNA structures in the regulation of basic cellular processes is an emerging field of research. Amongst local non-B DNA structures, G-quadruplexes (G4s) have gained in popularity during the last decade, and their presence and functional relevance at the DNA and RNA level has been demonstrated in a number of viral, bacterial, and eukaryotic genomes, including humans. Here, we performed the first systematic search of G4-forming sequences in all archaeal genomes available in the NCBI database. In this article, we investigate the presence and locations of G-quadruplex forming sequences using the G4Hunter algorithm. G-quadruplex-prone sequences were identified in all archaeal species, with highly significant differences in frequency, from 0.037 to 15.31 potential quadruplex sequences per kb. While G4 forming sequences were extremely abundant in Hadesarchaea archeon (strikingly, more than 50% of the Hadesarchaea archaeon isolate WYZ-LMO6 genome is a potential part of a G4-motif), they were very rare in the Parvarchaeota phylum. The presence of G-quadruplex forming sequences does not follow a random distribution with an over-representation in non-coding RNA, suggesting possible roles for ncRNA regulation. These data illustrate the unique and non-random localization of G-quadruplexes in Archaea. (10.3390/biom10091349)
    DOI : 10.3390/biom10091349
  • Development, structure, and bioengineering of the human corneal stroma: A review
    • Tidu Aurélien
    • Schanne-Klein Marie-Claire
    • Borderie Vincent
    Experimental Eye Research, Elsevier , 2020, 200, pp.108256 . (10.1016/j.exer.2020.108256)
    DOI : 10.1016/j.exer.2020.108256
  • In-place molecular preservation of cellulose in 5,000-year-old archaeological textiles
    • Reynaud Corentin
    • Thoury Mathieu
    • Dazzi Alexandre
    • Latour Gael
    • Scheel Mario
    • Li Jiayi
    • Thomas Ariane
    • Moulherat Christophe
    • Didier Aurore
    • Bertrand Loïc
    Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences , 2020, 117 (33), pp.19670-19676 . The understanding of fossilization mechanisms at the nanoscale remains extremely challenging despite its fundamental interest and its implications for paleontology, archaeology, geoscience, and environmental and material sciences. The mineralization mechanism by which cellulosic, keratinous, and silk tissues fossilize in the vicinity of archaeological metal artifacts offers the most exquisite preservation through a mechanism unexplored on the nanoscale. It is at the center of the vast majority of ancient textiles preserved under nonextreme conditions, known through extremely valuable fragments. Here we show the reconstruction of the nanoscale mechanism leading to the preservation of an exceptional collection of ancient cellulosic textiles recovered in the ancient Near East (4,000 to 5,000 years ago). We demonstrate that even the most mineralized fibers, which contain inorganic compounds throughout their histology, enclose preserved cel-lulosic remains in place. We evidence a process that combines the three steps of water transport of biocidal metal cations and soil solutes, degradation and loss of crystallinity of cellulosic polysaccharides, and silicification. cultural heritage | fossilization | cellulosic textiles | nanoimaging | synchrotron (10.1073/pnas.2004139117)
    DOI : 10.1073/pnas.2004139117
  • Dynamics of Cell Membrane Permeabilization by Saponins Using Terahertz Attenuated Total Reflection
    • Zheng Xiujun
    • Gallot Guilhem
    Biophysical Journal, Biophysical Society , 2020, 119 (4), pp.749-755 . Understanding the relevant parameters of the formation of pores during permeabilization is very challenging for medical applications. Several components are involved: the arrival of the permeabilizing molecules to the membrane, the efficiency of formation of the pores and their specific dynamics, and the flux of molecules through the plasma membrane. Using attenuated total reflection in the terahertz domain, we studied the dynamics of Madine-Darby canine kidney cells after permeabilization by saponin molecules. We developed an analytical model taking into account saponin molecule diffusion, cell geometry, cytosol molecule diffusion, and pore dynamics. We also studied the effect of possible pore overlapping on the cell membrane, introducing a dimensionless quantity that is the ratio between overlapping and diffusive effects. Pores are found to be static within 1 h after their creation, hinting that the diffusion of the saponin molecules to the membrane is the limiting factor in our experiments. (10.1016/j.bpj.2020.05.040)
    DOI : 10.1016/j.bpj.2020.05.040
  • Genome wide distribution of G-quadruplexes and their impact on gene expression in malaria parasites
    • Gazanion Elodie
    • Lacroix Laurent
    • Alberti Patrizia
    • Gurung Pratima
    • Wein Sharon
    • Cheng Mingpan
    • Mergny Jean‐louis
    • Gomes Ana Rita
    • Lopez‑rubio José‑juan
    PLoS Genetics, Public Library of Science , 2020, 16 (7), pp.e1008917 . Mechanisms of transcriptional control in malaria parasites are still not fully understood. The positioning patterns of G-quadruplex (G4) DNA motifs in the parasite's AT-rich genome, especially within the var gene family which encodes virulence factors, and in the vicinity of recombination hotspots, points towards a possible regulatory role of G4 in gene expression and genome stability. Here, we carried out the most comprehensive genome-wide survey, to date, of G4s in the Plasmodium falciparum genome using G4Hunter, which identifies G4 forming sequences (G4FS) considering their G-richness and G-skewness. We show an enrichment of G4FS in nucleosome-depleted regions and in the first exon of var genes, a pattern that is conserved within the closely related Laverania Plasmodium parasites. Under G4-stabilizing conditions, i.e., following treatment with pyridostatin (a high affinity G4 ligand), we show that a bona fide G4 found in the non-coding strand of var promoters modulates reporter gene expression. Furthermore, transcriptional profiling of pyridostatin-treated parasites, shows large scale perturbations, with deregulation affecting for instance the ApiAP2 family of transcription factors and genes involved in ribosome biogenesis. Overall, our study highlights G4s as important DNA secondary structures with a role in Plasmodium gene expression regulation, sub-telomeric recombination and var gene biology. (10.1371/journal.pgen.1008917)
    DOI : 10.1371/journal.pgen.1008917
  • Role of surface defects in colloidal cadmium selenide (CdSe) nanocrystals in the specificity of fluorescence quenching by metal cations
    • Mrad Randa
    • Poggi Mélanie
    • Ben Chaâbane Rafik
    • Negrerie Michel
    Journal of Colloid and Interface Science, Elsevier , 2020, 571, pp.368 - 377 . This study aimed to answer the question as whether crystal defects at the surface of soluble capped CdSe nanocrystals (or quantum dots, QDs) in water colloidal suspension are involved in the mechanism of fluorescence quenching induced by metal cations. Nanocrystals of CdSe were synthesized by an aqueous protocol, varying the ratio between the CdSe precursors and the grafted ligand mercaptosuccinic acid (MSA). Changing the MSA/CdSe ratio during synthesis impacts the crystal nucleation growth, which plays an important role in surface construction of CdSe QDs and changes the surface state. In this way, we could modulate the crystal surface defects of CdSe, as verified by analysis of the individual bands which constitute the emission spectra and are associated with different relaxation processes. We found that the various tested metal cations, which interact in solution with the MSA ligand grafted on the QDs, quench their fluorescence differently, depending on the MSA/CdSe ratio used in synthesis. The crystal defects modulate the excitonic relaxation in CdSe and we demonstrated here that the surface defects intervene in the quenching of QDs induced by the binding of cations. (10.1016/j.jcis.2020.03.058)
    DOI : 10.1016/j.jcis.2020.03.058
  • Monitoring the molecular composition of live cells exposed to electric pulses via label-free optical methods
    • Azan Antoine
    • Grognot Marianne
    • García Sánchez Tomás
    • Descamps Lucie
    • Untereiner Valérie
    • Piot Olivier
    • Gallot Guilhem
    • Mir Lluis M
    Scientific Reports, Nature Publishing Group , 2020, 10 (1), pp.10471 . The permeabilization of the live cells membrane by the delivery of electric pulses has fundamental interest in medicine, in particular in tumors treatment by electrochemotherapy. Since underlying mechanisms are still not fully understood, we studied the impact of electric pulses on the biochemical composition of live cells thanks to label-free optical methods: confocal Raman microspectroscopy and terahertz microscopy. A dose effect was observed after cells exposure to different field intensities and a major impact on cell peptide/protein content was found. Raman measurements reveal that protein structure and/or environment are modified by the electric pulses while terahertz measurements suggest a leakage of proteins and other intracellular compounds. We show that Raman and terahertz modalities are a particularly attractive complement to fluorescence microscopy which is the reference optical technique in the case of electropermeabilization. Finally, we propose an analytical model for the influx and efflux of non-permeant molecules through transiently (electro)permeabilized cell membranes. (10.1038/s41598-020-67402-x)
    DOI : 10.1038/s41598-020-67402-x
  • pKa Calculations with the Polarizable Drude Force Field and Poisson–Boltzmann Solvation Model
    • Aleksandrov Alexey
    • Roux Benoît
    • Mackerell Alexander D.
    Journal of Chemical Theory and Computation, American Chemical Society , 2020, 16 (7), pp.4655–4668 . Electronic polarization effects have been suggested to play an important role in proton binding to titratable residues in proteins. In this work, we describe a new computational method for pKa calculations, using Monte Carlo (MC) simulations to sample protein protonation states with the Drude polarizable force field and Poisson–Boltzmann (PB) continuum electrostatic solvent model. While the most populated protonation states at the selected pH, corresponding to residues that are half-protonated at that pH, are sampled using the exact relative free energies computed with Drude particles optimized in the field of the PB implicit solvation model, we introduce an approximation for the protein polarization of low-populated protonation states to reduce the computational cost. The highly populated protonation states used to compute the polarization and pKa’s are then iteratively improved until convergence. It is shown that for lysozyme, when considering 9 of the 18 titratable residues, the new method converged within two iterations with computed pKa’s differing only by 0.02 pH units from pKa’s estimated with the exact approach. Application of the method to predict pKa’s of 94 titratable side chains in 8 proteins shows the Drude-PB model to produce physically more correct results as compared to the additive CHARMM36 (C36) force field (FF). With a dielectric constant of two assigned to the protein interior the Root Mean Square (RMS) deviation between computed and experimental pKa’s is 2.07 and 3.19 pH units with the Drude and C36 models, respectively, and the RMS deviation using the Drude-PB model is relatively insensitive to the choice of the internal dielectric constant in contrast to the additive C36 model. At the higher internal dielectric constant of 20, pKa’s computed with the additive C36 model converge to the results obtained with the Drude polarizable force field, indicating the need to artificially overestimate electrostatic screening in a nonphysical way with the additive FF. In addition, inclusion of both syn and anti orientations of the proton in the neutral state of acidic groups is shown to yield improved agreement with experiment. The present work, which is the first example of the use of a polarizable model for the prediction of pKa’s in proteins, shows that the use of a polarizable model represents a more physically correct model for the treatment of electrostatic contributions to pKa shifts in proteins. (10.1021/acs.jctc.0c00111)
    DOI : 10.1021/acs.jctc.0c00111
  • Electronic measurement of femtosecond time delays for arbitrary-detuning asynchronous optical sampling
    • Antonucci Laura
    • Solinas Xavier
    • Bonvalet Adeline
    • Joffre Manuel
    Optics Express, Optical Society of America - OSA Publishing , 2020, 28 (12), pp.18251 . (10.1364/OE.393887)
    DOI : 10.1364/OE.393887
  • Enabling large-scale genome editing at repetitive elements by reducing DNA nicking
    • Smith Cory J
    • Castanon Oscar
    • Said Khaled
    • Volf Verena
    • Khoshakhlagh Parastoo
    • Hornick Amanda
    • Ferreira Raphael
    • Wu Chun-Ting
    • Güell Marc
    • Garg Shilpa
    • Ng Alex H M
    • Myllykallio Hannu
    • Church George M
    Nucleic Acids Research, Oxford University Press , 2020, 48 (9), pp.5183-5195 . To extend the frontier of genome editing and enable editing of repetitive elements of mammalian genomes, we made use of a set of dead-Cas9 base editor (dBE) variants that allow editing at tens of thousands of loci per cell by overcoming the cell death associated with DNA double-strand breaks and single-strand breaks. We used a set of gRNAs targeting repetitive elements-ranging in target copy number from about 32 to 161 000 per cell. dBEs enabled survival after large-scale base editing, allowing targeted mutations at up to ∼13 200 and ∼12 200 loci in 293T and human induced pluripotent stem cells (hiP-SCs), respectively, three orders of magnitude greater than previously recorded. These dBEs can overcome current on-target mutation and toxicity barriers that prevent cell survival after large-scale genome engineering. (10.1093/nar/gkaa239)
    DOI : 10.1093/nar/gkaa239
  • Corneal stromal stem cells restore transparency after N 2 injury in mice
    • Ghoubay Djida
    • Borderie Marie
    • Grieve Kate
    • Martos Raphaël
    • Bocheux Romain
    • Nguyen Thu-Mai
    • Callard Patrice
    • Chédotal Alain
    • Borderie Vincent M.
    Stem Cells Translational Medicine, Wiley , 2020, 9 (8), pp.917-935 . Corneal scarring associated with various corneal conditions is a leading cause of blindness worldwide. The present study aimed to test the hypothesis that corneal stromal stem cells have a therapeutic effect and are able to restore the extracellular matrix organization and corneal transparency in vivo. We first developed a mouse model of corneal stromal scar induced by liquid nitrogen (N2 ) application. We then reversed stromal scarring by injecting mouse or human corneal stromal stem cells in injured cornea. To characterize the mouse model developed in this study and the therapeutic effect of corneal stromal stem cells, we used a combination of in vivo (slit lamp, optical coherence tomography, in vivo confocal microscopy, optical coherence tomography shear wave elastography, and optokinetic tracking response) and ex vivo (full field optical coherence microscopy, flow cytometry, transmission electron microscopy, and histology) techniques. The mouse model obtained features early inflammation, keratocyte apoptosis, keratocyte transformation into myofibroblasts, collagen type III synthesis, impaired stromal ultrastructure, corneal stromal haze formation, increased corneal rigidity, and impaired visual acuity. Injection of stromal stem cells in N2 -injured cornea resulted in improved corneal transparency associated with corneal stromal stem cell migration and growth in the recipient stroma, absence of inflammatory response, recipient corneal epithelial cell growth, decreased collagen type III stromal content, restored stromal ultrastructure, decreased stromal haze, decreased corneal rigidity, and improved vision. Our study demonstrates the ability of corneal stromal stem cells to promote regeneration of transparent stromal tissue after corneal scarring induced by liquid nitrogen. (10.1002/sctm.19-0306)
    DOI : 10.1002/sctm.19-0306
  • Fast In Vivo Imaging of SHG Nanoprobes with Multiphoton Light-Sheet Microscopy
    • Malkinson Guy
    • Mahou Pierre
    • Chaudan Élodie
    • Gacoin Thierry
    • Sonay Ali
    • Pantazis Periklis
    • Beaurepaire Emmanuel
    • Supatto Willy
    ACS photonics, American Chemical Society , 2020, 7 (4), pp.1036-1049 . Two-photon light-sheet microscopy (2P-SPIM) provides a unique combination of advantages for fast and deep fluorescence imaging in live tissues. Detecting coherent signals such as second-harmonic generation (SHG) in 2P-SPIM in addition to fluorescence would open further imaging opportunities. However, light-sheet microscopy involves an orthogonal configuration of illumination and detection that questions the ability to detect coherent signals. Indeed, coherent scattering from micron-sized structures occurs predominantly along the illumination beam. By contrast, point-like sources such as SHG nanocrystals can efficiently scatter light in multiple directions and be detected using the orthogonal geometry of a light-sheet microscope. This study investigates the suitability of SHG light-sheet microscopy (SHG-SPIM) for fast imaging of SHG nanoprobes. Parameters that govern the detection efficiency of KTiOPO 4 and BaTiO 3 nanocrystals using SHG-SPIM are investigated theoretically and experimentally. The effects of incident polarization, detection numerical aperture, nanocrystal rotational motion, and second-order susceptibility tensor symmetries on the detectability of SHG nanoprobes in this specific geometry are clarified. Guidelines for optimizing SHG-SPIM imaging are established, enabling fast in vivo light-sheet imaging combining SHG and two-photon excited fluorescence. Finally, microangiography was achieved in live zebrafish embryos by SHG imaging at up to 180 frames per second and single-particle tracking of SHG nanoprobes in the blood flow. (10.1021/acsphotonics.9b01749)
    DOI : 10.1021/acsphotonics.9b01749
  • Native Collagen: Electrospinning of Pure, Cross-Linker-Free, Self-Supported Membrane
    • Dems Dounia
    • Rodrigues da Silva Julien
    • Hélary Christophe
    • Wien Frank
    • Marchand Marion
    • Debons Nicolas
    • Muller Laurent
    • Chen Yong
    • Schanne-Klein Marie-Claire
    • Laberty-Robert Christel
    • Krins Natacha
    • Aimé Carole
    ACS Applied Bio Materials, ACS Publications , 2020 . Rebuilding biological environments is crucial when facing the challenges of fundamental and biomedical research. Thus, preserving the native state of biomolecules is essential. We use electrospinning (ES), which is an extremely promising method for the preparation of fibrillar membranes to mimic the ECM of native tissues. Here, we report for the first time (1) the ES of pure and native collagen into a self-supported membrane in absence of crosslinker and polymer support, (2) the preservation of the membrane integrity in hydrated media in absence of crosslinker and (3) the preservation of the native molecular structure and recovery of the hierarchical assembly of collagen. We use a multiscale approach to characterize collagen native structure at the molecular level using circular dichroism, and to investigate collagen hierarchical organization within the self-supported membrane using a combination of multiphoton and electron microscopies. Finally, we show that the membranes are perfectly suited for cell adhesion and spreading, making them very promising candidates for the development of biomaterials and finding applications in biomedical research. (10.1021/acsabm.0c00006)
    DOI : 10.1021/acsabm.0c00006