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For hemophilia and thalassemia, a new era of ‘one-and-done’ gene therapies has arrived
Cormac SheridanÂÂ
doi : 10.1038/s41587-022-01555-0
Volume 40 Issue 11, November 2022
Cow-less milk: the rising tide of animal-free dairy attracts big players
Emily WaltzÂÂ
Drug pipeline 3Q22 � rare disease and Alzheimer’s treatments
Laura DeFrancescoÂÂ
Nature Biotechnology’s academic spinouts 2021
Michael Eisenstein, Ken Garber, Esther Landhuis & Laura DeFrancescoÂ
The Coronavirus Standards Working Group’s roadmap for improved population testing
Tim Mercer, Neil Almond, Michael A. Crone, Patrick S. G. Chain, Alina Deshpande, Deepa Eveleigh, Paul Freemont, Sebastien Fuchs, Russell Garlick, Jim Huggett, Martin Kammel, Po-E Li, Mojca Milavec, Elizabeth M. Marlowe, Denise M. O’Sullivan, Mark Page, Gary A. Pestano, Sara Suliman, Birgitte Simen, John J. Sninsky, Lynne Sopchak, Cristina M. Tato, Peter M. Vallone, Jo Vandesompele, …Marc SalitÂ
Has the PTAB made a difference in drug settlements and generic entry?
Erik Hovenkamp, Jorge Lemus, Arti Rai & Saurabh VishnubhakatÂ
Organelle-like scaffolds in bacteria for synthetic biology
Natalie G. BarnesÂÂ
Single-cell RNA-seq relates GWAS variants to disease risk
Anne DörrÂÂ
Spatial transcriptomics with light barcodes in intact tissues
Alexandra DespangÂÂ
A language model beats alphafold2 on orphans
Jennifer M. Michaud, Ali Madani & James S. FraserÂ
First liver transplantation using a graft maintained ex vivo for several days
Towards the non-invasive imaging of brain networks and functions at high resolution
Measuring SARS-CoV-2 T cell immunity with a scalable qPCR-based assay
Unlocking the promise of mRNA therapeutics
Eduarde Rohner, Ran Yang, Kylie S. Foo, Alexander Goedel & Kenneth R. ChienÂ
doi : 10.1038/s41587-022-01491-z
The extraordinary success of mRNA vaccines against coronavirus disease 2019 (COVID-19) has renewed interest in mRNA as a means of delivering therapeutic proteins. Early clinical trials of mRNA therapeutics include studies of paracrine vascular endothelial growth factor (VEGF) mRNA for heart failure and of CRISPR–Cas9 mRNA for a congenital liver-specific storage disease.
Directed evolution and selection of biostable l-DNA aptamers with a mirror-image DNA polymerase
Ji Chen, Mengyin Chen & Ting F. ZhuÂ
doi : 10.1038/s41587-022-01337-8
Mirror-image aptamers made from chirally inverted nucleic acids are nuclease-resistant and exceptionally biostable, opening up opportunities for unique applications.
Transplantation of a human liver following 3 days of ex situ normothermic preservation
Pierre-Alain Clavien, Philipp Dutkowski, Matteo Mueller, Dilmurodjon Eshmuminov, Lucia Bautista Borrego, Achim Weber, Beat Muellhaupt, Richard X. Sousa Da Silva, Brian R. Burg, Philipp Rudolf von Rohr, Martin J. Schuler, Dustin Becker, Max Hefti & Mark W. TibbittÂ
doi : 10.1038/s41587-022-01354-7
Current organ preservation methods provide a narrow window (usually <12 hours) to assess, transport and implant donor grafts for human transplantation. Here we report the transplantation of a human liver discarded by all centers, which could be preserved for several days using ex situ normothermic machine perfusion.
Single-sequence protein structure prediction using a language model and deep learning
Ratul Chowdhury, Nazim Bouatta, Surojit Biswas, Christina Floristean, Anant Kharkar, Koushik Roy, Charlotte Rochereau, Gustaf Ahdritz, Joanna Zhang, George M. Church, Peter K. Sorger & Mohammed AlQuraishiÂ
doi : 10.1038/s41587-022-01432-w
AlphaFold2 and related computational systems predict protein structure using deep learning and co-evolutionary relationships encoded in multiple sequence alignments (MSAs). Despite high prediction accuracy achieved by these systems, challenges remain in (1) prediction of orphan and rapidly evolving proteins for which an MSA cannot be generated; (2) rapid exploration of designed structures; and (3) understanding the rules governing spontaneous polypeptide folding in solution.
Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression
Shaolong Cao, Jennifer R. Wang, Shuangxi Ji, Peng Yang, Yaoyi Dai, Shuai Guo, Matthew D. Montierth, John Paul Shen, Xiao Zhao, Jingxiao Chen, Jaewon James Lee, Paola A. Guerrero, Nicholas Spetsieris, Nikolai Engedal, Sinja Taavitsainen, Kaixian Yu, Julie Livingstone, Vinayak Bhandari, Shawna M. Hubert, Najat C. Daw, P. Andrew Futreal, Eleni Efstathiou, Bora Lim, Andrea Viale, Jianjun Zhang, Matti Nykter, Bogdan A. Czerniak, Powel H. Brown, Charles Swanton, Pavlos Msaouel, Anirban Maitra, Scott Kopetz, Peter Campbell, Terence P. Speed, Paul C. Boutros, Hongtu Zhu, Alfonso Urbanucci, Jonas Demeulemeester, Peter Van Loo & Wenyi WangÂ
doi : 10.1038/s41587-022-01342-x
Single-cell RNA sequencing studies have suggested that total mRNA content correlates with tumor phenotypes. Technical and analytical challenges, however, have so far impeded at-scale pan-cancer examination of total mRNA content.
Genome-wide mapping of somatic mutation rates uncovers drivers of cancer
Maxwell A. Sherman, Adam U. Yaari, Oliver Priebe, Felix Dietlein, Po-Ru Loh & Bonnie BergerÂ
doi : 10.1038/s41587-022-01353-8
Identification of cancer driver mutations that confer a proliferative advantage is central to understanding cancer; however, searches have often been limited to protein-coding sequences and specific non-coding elements (for example, promoters) because of the challenge of modeling the highly variable somatic mutation rates observed across tumor genomes.
Variant to function mapping at single-cell resolution through network propagation
Fulong Yu, Liam D. Cato, Chen Weng, L. Alexander Liggett, Soyoung Jeon, Keren Xu, Charleston W. K. Chiang, Joseph L. Wiemels, Jonathan S. Weissman, Adam J. de Smith & Vijay G. SankaranÂ
doi : 10.1038/s41587-022-01341-y
Genome-wide association studies in combination with single-cell genomic atlases can provide insights into the mechanisms of disease-causal genetic variation. However, identification of disease-relevant or trait-relevant cell types, states and trajectories is often hampered by sparsity and noise, particularly in the analysis of single-cell epigenomic data.
Spatiotemporal multiplexed immunofluorescence imaging of living cells and tissues with bioorthogonal cycling of fluorescent probes
Jina Ko, Martin Wilkovitsch, Juhyun Oh, Rainer H. Kohler, Evangelia Bolli, Mikael J. Pittet, Claudio Vinegoni, David B. Sykes, Hannes Mikula, Ralph Weissleder & Jonathan C. T. CarlsonÂ
doi : 10.1038/s41587-022-01339-6
Cells in complex organisms undergo frequent functional changes, but few methods allow comprehensive longitudinal profiling of living cells. Here we introduce scission-accelerated fluorophore exchange (SAFE), a method for multiplexed temporospatial imaging of living cells with immunofluorescence.
Deep tissue multi-photon imaging using adaptive optics with direct focus sensing and shaping
Zhongya Qin, Zhentao She, Congping Chen, Wanjie Wu, Jackie K. Y. Lau, Nancy Y. Ip & Jianan Y. QuÂ
doi : 10.1038/s41587-022-01343-w
High-resolution optical imaging deep in tissues is challenging because of optical aberrations and scattering of light caused by the complex structure of living matter. Here we present an adaptive optics three-photon microscope based on analog lock-in phase detection for focus sensing and shaping (ALPHA-FSS).
A red light–responsive photoswitch for deep tissue optogenetics
Yuto Kuwasaki, Kazushi Suzuki, Gaigai Yu, Shota Yamamoto, Takahiro Otabe, Yuki Kakihara, Michiru Nishiwaki, Keita Miyake, Keiji Fushimi, Ramsey Bekdash, Yoshihiro Shimizu, Rei Narikawa, Takahiro Nakajima, Masayuki Yazawa & Moritoshi SatoÂ
doi : 10.1038/s41587-022-01351-w
Red light penetrates deep into mammalian tissues and has low phototoxicity, but few optogenetic tools that use red light have been developed. Here we present MagRed, a red light–activatable photoswitch that consists of a red light–absorbing bacterial phytochrome incorporating a mammalian endogenous chromophore, biliverdin and a photo-state-specific binder that we developed using Affibody library selection.
Rapid, scalable assessment of SARS-CoV-2 cellular immunity by whole-blood PCR
Megan Schwarz, Denis Torre, Daniel Lozano-Ojalvo, Anthony T. Tan, Tommaso Tabaglio, Slim Mzoughi, Rodrigo Sanchez-Tarjuelo, Nina Le Bert, Joey Ming Er Lim, Sandra Hatem, Kevin Tuballes, Carmen Camara, Eduardo Lopez-Granados, Estela Paz-Artal, Rafael Correa-Rocha, Alberto Ortiz, Marcos Lopez-Hoyos, Jose Portoles, Isabel Cervera, Maria Gonzalez-Perez, Irene Bodega-Mayor, Patricia Conde, Jesús Oteo-Iglesias, Alberto M. Borobia, Antonio J. Carcas, Jesús FrÃÂas, Cristóbal Belda-Iniesta, Jessica S. Y. Ho, Kemuel Nunez, Saboor Hekmaty, Kevin Mohammed, William M. Marsiglia, Juan Manuel Carreño, Arvin C. Dar, Cecilia Berin, Giuseppe Nicoletti, Isabella Della Noce, Lorenzo Colombo, Cristina Lapucci, Graziano Santoro, Maurizio Ferrari, Kai Nie, Manishkumar Patel, Vanessa Barcessat, Sacha Gnjatic, Jocelyn Harris, Robert Sebra, Miriam Merad, Florian Krammer, Seunghee Kim-schulze, Ivan Marazzi, Antonio Bertoletti, Jordi Ochando & Ernesto GuccioneÂ
doi : 10.1038/s41587-022-01347-6
Fast, high-throughput methods for measuring the level and duration of protective immune responses to SARS-CoV-2 are needed to anticipate the risk of breakthrough infections. Here we report the development of two quantitative PCR assays for SARS-CoV-2-specific T cell activation.
Author Correction: Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients
Tobias Deuse, Xiaomeng Hu, Alessia Gravina, Dong Wang, Grigol Tediashvili, Chandrav De, William O. Thayer, Angela Wahl, J. Victor Garcia, Hermann Reichenspurner, Mark M. Davis, Lewis L. Lanier & Sonja SchrepferÂ
Author Correction: Massively parallel phenotyping of coding variants in cancer with Perturb-seq
Oana Ursu, James T. Neal, Emily Shea, Pratiksha I. Thakore, Livnat Jerby-Arnon, Lan Nguyen, Danielle Dionne, Celeste Diaz, Julia Bauman, Mariam Mounir Mosaad, Christian Fagre, April Lo, Maria McSharry, Andrew O. Giacomelli, Seav Huong Ly, Orit Rozenblatt-Rosen, William C. Hahn, Andrew J. Aguirre, Alice H. Berger, Aviv Regev & Jesse S. BoehmÂ
Publisher Correction: Single-sequence protein structure prediction using a language model and deep learning
Ratul Chowdhury, Nazim Bouatta, Surojit Biswas, Christina Floristean, Anant Kharkar, Koushik Roy, Charlotte Rochereau, Gustaf Ahdritz, Joanna Zhang, George M. Church, Peter K. Sorger & Mohammed AlQuraishiÂ
Retraction Note: Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN
Kevin D. Foust, Xueyong Wang, Vicki L. McGovern, Lyndsey Braun, Adam K. Bevan, Amanda M. Haidet, Thanh T. Le, Pablo R. Morales, Mark M. Rich, Arthur H. M. Burghes & Brian K. KasparÂ
Mind the gap: closing the growing chasm between academia and industry
Alexander J. Spicer, Pierre-Albert Colcomb & Ann KraftÂ
