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Generating ‘smarter’ biotechnology

doi : 10.1038/s41587-023-01695-x

Volume 41 Issue 2, February 2023

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Industry appetite for natural killer cells intensifies

Cormac Sheridan 

doi : 10.1038/s41587-023-01671-5

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Small innovators advance microbes as alternatives to chemical crop sprays

Emily Waltz 

doi : 10.1038/s41587-023-01670-6

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Putting CRISPR into African hands to future-proof crops

Linda Nordling 

doi : 10.1038/s41587-023-01668-0

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Drug pipeline 4Q22 � sticking around

John Hodgson 

doi : 10.1038/s41587-023-01660-8

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2022 – toughing out the trough

John Hodgson 

doi : 10.1038/s41587-023-01661-7

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Fresh from the biotech pipeline: fewer approvals, but biologics gain share

Melanie Senior 

doi : 10.1038/s41587-022-01630-6

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Delivering 3 billion doses of Comirnaty in 2021

Nicholas Warne, Margaret Ruesch, Pamela Siwik, Paul Mensah, John Ludwig, Michael Hripcsak, Ranga Godavarti, Andrew Prigodich & Mikael DolstenÂ

doi : 10.1038/s41587-022-01643-1

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Drug licensing as evidence of evolution, diffusion and catch-up in East Asia

Jianan HuangÂ

doi : 10.1038/s41587-023-01659-1

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Capturing haplotype variation in populations using pangenome references

Jared B. Fudge 

doi : 10.1038/s41587-023-01691-1

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Consequences of cis-regulatory sequence variation

Jared B. Fudge 

doi : 10.1038/s41587-023-01692-0

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DISCO-MS combines spatial proteomics with whole-organ imaging

Anne Doerr 

doi : 10.1038/s41587-023-01699-7

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Capturing the diversity of protein modifications on presented tumor antigens

doi : 10.1038/s41587-022-01465-1

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A competitive precision CRISPR method to identify the fitness effects of transcription factor binding sites

Päivi Pihlajamaa, Otto Kauko, Biswajyoti Sahu, Teemu Kivioja & Jussi TaipaleÂ

doi : 10.1038/s41587-022-01444-6

Here we describe a competitive genome editing method that measures the effect of mutations on molecular functions, based on precision CRISPR editing using template libraries with either the original or altered sequence, and a sequence tag, enabling direct comparison between original and mutated cells.

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Mostly natural sequencing-by-synthesis for scRNA-seq using Ultima sequencing

Sean K. Simmons, Gila Lithwick-Yanai, Xian Adiconis, Florian Oberstrass, Nika Iremadze, Kathryn Geiger-Schuller, Pratiksha I. Thakore, Chris J. Frangieh, Omer Barad, Gilad Almogy, Orit Rozenblatt-Rosen, Aviv Regev, Doron Lipson & Joshua Z. LevinÂ

doi : 10.1038/s41587-022-01452-6

Here we introduce a mostly natural sequencing-by-synthesis (mnSBS) method for single-cell RNA sequencing (scRNA-seq), adapted to the Ultima genomics platform, and systematically benchmark it against current scRNA-seq technology.

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Multiplexed, single-molecule, epigenetic analysis of plasma-isolated nucleosomes for cancer diagnostics

Vadim Fedyuk, Nir Erez, Noa Furth, Olga Beresh, Ekaterina Andreishcheva, Abhijeet Shinde, Daniel Jones, Barak Bar Zakai, Yael Mavor, Tamar Peretz, Ayala Hubert, Jonathan E. Cohen, Azzam Salah, Mark Temper, Albert Grinshpun, Myriam Maoz, Aviad Zick, Guy Ron & Efrat ShemaÂ

doi : 10.1038/s41587-022-01447-3

The analysis of cell-free DNA (cfDNA) in plasma provides information on pathological processes in the body. Blood cfDNA is in the form of nucleosomes, which maintain their tissue- and cancer-specific epigenetic state.

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Scalable in situ single-cell profiling by electrophoretic capture of mRNA using EEL FISH

Lars E. Borm, Alejandro Mossi Albiach, Camiel C. A. Mannens, Jokubas Janusauskas, Ceren Özgün, David Fernández-García, Rebecca Hodge, Francisca Castillo, Charlotte R. H. Hedin, Eduardo J. Villablanca, Per Uhlén, Ed S. Lein, Simone Codeluppi & Sten LinnarssonÂ

doi : 10.1038/s41587-022-01455-3

Methods to spatially profile the transcriptome are dominated by a trade-off between resolution and throughput. Here we develop a method named Enhanced ELectric Fluorescence in situ Hybridization (EEL FISH) that can rapidly process large tissue samples without compromising spatial resolution.

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DeepConsensus improves the accuracy of sequences with a gap-aware sequence transformer

Gunjan Baid, Daniel E. Cook, Kishwar Shafin, Taedong Yun, Felipe Llinares-López, Quentin Berthet, Anastasiya Belyaeva, Armin Töpfer, Aaron M. Wenger, William J. Rowell, Howard Yang, Alexey Kolesnikov, Waleed Ammar, Jean-Philippe Vert, Ashish Vaswani, Cory Y. McLean, Maria Nattestad, Pi-Chuan Chang & Andrew CarrollÂ

doi : 10.1038/s41587-022-01435-7

Circular consensus sequencing with Pacific Biosciences (PacBio) technology generates long (10–25 kilobases), accurate ‘HiFi’ reads by combining serial observations of a DNA molecule into a consensus sequence.

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Post-translational modifications reshape the antigenic landscape of the MHC I immunopeptidome in tumors

Assaf Kacen, Aaron Javitt, Matthias P. Kramer, David Morgenstern, Tomer Tsaban, Merav D. Shmueli, Guo Ci Teo, Felipe da Veiga Leprevost, Eilon Barnea, Fengchao Yu, Arie Admon, Lea Eisenbach, Yardena Samuels, Ora Schueler-Furman, Yishai Levin, Alexey I. Nesvizhskii & Yifat MerblÂ

doi : 10.1038/s41587-022-01464-2

Post-translational modification (PTM) of antigens provides an additional source of specificities targeted by immune responses to tumors or pathogens, but identifying antigen PTMs and assessing their role in shaping the immunopeptidome is challenging.

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Human ureteric bud organoids recapitulate branching morphogenesis and differentiate into functional collecting duct cell types

Min Shi, Kyle W. McCracken, Ankit B. Patel, Weitao Zhang, Lioba Ester, M. Todd Valerius & Joseph V. BonventreÂ

doi : 10.1038/s41587-022-01429-5

Directed differentiation of human pluripotent stem cells (hPSCs) into functional ureteric and collecting duct (CD) epithelia is essential to kidney regenerative medicine. Here we describe highly efficient, serum-free differentiation of hPSCs into ureteric bud (UB) organoids and functional CD cells.

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Engineering circular RNA for enhanced protein production

Robert Chen, Sean K. Wang, Julia A. Belk, Laura Amaya, Zhijian Li, Angel Cardenas, Brian T. Abe, Chun-Kan Chen, Paul A. Wender & Howard Y. ChangÂ

doi : 10.1038/s41587-022-01393-0

Circular RNAs (circRNAs) are stable and prevalent RNAs in eukaryotic cells that arise from back-splicing.

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Modular cytokine receptor-targeting chimeras for targeted degradation of cell surface and extracellular proteins

Katarina Pance, Josef A. Gramespacher, James R. Byrnes, Fernando Salangsang, Juan-Antonio C. Serrano, Adam D. Cotton, Veronica Steri & James A. WellsÂ

doi : 10.1038/s41587-022-01456-2

Targeted degradation of cell surface and extracellular proteins via lysosomal delivery is an important means to modulate extracellular biology. However, these approaches have limitations due to lack of modularity, ease of development, restricted tissue targeting and applicability to both cell surface and extracellular proteins.

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Real-time denoising enables high-sensitivity fluorescence time-lapse imaging beyond the shot-noise limit

Xinyang Li, Yixin Li, Yiliang Zhou, Jiamin Wu, Zhifeng Zhao, Jiaqi Fan, Fei Deng, Zhaofa Wu, Guihua Xiao, Jing He, Yuanlong Zhang, Guoxun Zhang, Xiaowan Hu, Xingye Chen, Yi Zhang, Hui Qiao, Hao Xie, Yulong Li, Haoqian Wang, Lu Fang & Qionghai DaiÂ

doi : 10.1038/s41587-022-01450-8

A fundamental challenge in fluorescence microscopy is the photon shot noise arising from the inevitable stochasticity of photon detection. Noise increases measurement uncertainty and limits imaging resolution, speed and sensitivity.

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Author Correction: Engineering circular RNA for enhanced protein production

Robert Chen, Sean K. Wang, Julia A. Belk, Laura Amaya, Zhijian Li, Angel Cardenas, Brian T. Abe, Chun-Kan Chen, Paul A. Wender & Howard Y. ChangÂ

doi : 10.1038/s41587-022-01472-2

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Retaining postdocs by recognizing their worth

Esra Yalcin, Rosa Martinez-Corral & Mayank ChughÂ

doi : 10.1038/s41587-023-01656-4

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Fourth-quarter biotech job picture

Michael Francisco 

doi : 10.1038/s41587-023-01666-2

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