scholarly journals Engineered peptide ligases for cell signaling and bioconjugation

2020 ◽  
Vol 48 (3) ◽  
pp. 1153-1165
Author(s):  
Clara L. Frazier ◽  
Amy M. Weeks
Keyword(s):  
Protein Engineering ◽  
Specific Protein ◽  
Biological Research ◽  
Biological Applications ◽  
Site Specific ◽  
Challenges And Opportunities ◽  
Future Challenges ◽  
Natural Peptide ◽  
Further Development ◽  
Peptide Ligation

Enzymes that catalyze peptide ligation are powerful tools for site-specific protein bioconjugation and the study of cellular signaling. Peptide ligases can be divided into two classes: proteases that have been engineered to favor peptide ligation, and protease-related enzymes with naturally evolved peptide ligation activity. Here, we provide a review of key natural peptide ligases and proteases engineered to favor peptide ligation activity. We cover the protein engineering approaches used to generate and improve these tools, along with recent biological applications, advantages, and limitations associated with each enzyme. Finally, we address future challenges and opportunities for further development of peptide ligases as tools for biological research.

scholarly journals Designer membraneless organelles enable codon reassignment of selected mRNAs in eukaryotes

Science ◽  
2019 ◽  
Vol 363 (6434) ◽  
pp. eaaw2644 ◽  
Author(s):  
Christopher D. Reinkemeier ◽  
Gemma Estrada Girona ◽  
Edward A. Lemke
Keyword(s):  
Protein Engineering ◽  
Messenger Rna ◽  
Stop Codon ◽  
Specific Protein ◽  
Codon Reassignment ◽  
Entire Genome ◽  
Site Specific ◽  
Cellular Processes ◽  
Spatial Targeting ◽  
Rna Targeting

Nature regulates interference between cellular processes—allowing more complexity of life—by confining specific functions to organelles. Inspired by this concept, we designed an artificial organelle dedicated to protein engineering. We generated a membraneless organelle to translate only one type of messenger RNA—by recruiting an RNA-targeting system, stop codon–suppression machinery, and ribosomes—by means of phase separation and spatial targeting. This enables site-specific protein engineering with a tailored noncanonical function in response to one specific codon in the entire genome only in the protein of choice. Our results demonstrate a simple yet effective approach to the generation of artificial organelles that provides a route toward customized orthogonal translation and protein engineering in semisynthetic eukaryotic cells.

Systematic Engineering of a Protein Nanocage for High-Yield, Site-Specific Modification

2018 ◽  
Author(s):  
Daniel D. Brauer ◽  
Emily C. Hartman ◽  
Daniel L.V. Bader ◽  
Zoe N. Merz ◽  
Danielle Tullman-Ercek ◽  
...  
Keyword(s):  
Small Molecules ◽  
Protein Modification ◽  
Positive Charge ◽  
Specific Protein ◽  
High Yield ◽  
Site Specific ◽  
Protein Cage ◽  
Protein Carriers ◽  
Site Selective ◽  
Targeted Library

<div> <p>Site-specific protein modification is a widely-used strategy to attach drugs, imaging agents, or other useful small molecules to protein carriers. N-terminal modification is particularly useful as a high-yielding, site-selective modification strategy that can be compatible with a wide array of proteins. However, this modification strategy is incompatible with proteins with buried or sterically-hindered N termini, such as virus-like particles like the well-studied MS2 bacteriophage coat protein. To assess VLPs with improved compatibility with these techniques, we generated a targeted library based on the MS2-derived protein cage with N-terminal proline residues followed by three variable positions. We subjected the library to assembly, heat, and chemical selections, and we identified variants that were modified in high yield with no reduction in thermostability. Positive charge adjacent to the native N terminus is surprisingly beneficial for successful extension, and over 50% of the highest performing variants contained positive charge at this position. Taken together, these studies described nonintuitive design rules governing N-terminal extensions and identified successful extensions with high modification potential.</p> </div>

scholarly journals Dutch Public health Foresight study 2018/20

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
H Hilderink
Keyword(s):  
Public Health ◽  
Health Care ◽  
Health Care Expenditures ◽  
Living Environment ◽  
Societal Challenges ◽  
Challenges And Opportunities ◽  
Future Challenges ◽  
National Prevention ◽  
Business As Usual ◽  
Insight Into

Abstract The four-year Public Health Foresight Study (VTV) provides insight into the most important societal challenges for public health and health care in the Netherlands. The seventh edition of the Dutch Public Health Foresight study was published in 2018, with an update in 2020. In this update a business-as-usual or Trend Scenario was developed using 2018 as a base year. In the trend scenario demographic and epidemiological projections have been used to depict the future trends regarding ageing, health, disease, health behaviors, health expenditures and health inequalities. Next, these trends are used to identify the most important future challenges and opportunities for public health. In the 2020 update, special attentions is given to climate change and the local living environment and their impacts and interaction with public health outcomes. Trends in lifestyle-related lifestyle show both positive (smoking prevalence) and negative (overweight prevalence) future developments. Dementia will be the leading cause of mortality and disease burden in 2040 by far. Health care expenditures will double by 2040, with cancers showing the most rapid growth of all disease groups. The insights of this study are directly used as input for the National Health Policy Memorandum and for the National Prevention Accord.

scholarly journals Unconventional Materials Processing Using Spark Plasma Sintering

Ceramics ◽  
2021 ◽  
Vol 4 (1) ◽  
pp. 20-40
Author(s):  
Ambreen Nisar ◽  
Cheng Zhang ◽  
Benjamin Boesl ◽  
Arvind Agarwal
Keyword(s):  
Spark Plasma Sintering ◽  
Real Life ◽  
Functional Materials ◽  
Research Field ◽  
Advanced Materials ◽  
Plasma Sintering ◽  
Challenges And Opportunities ◽  
Future Challenges ◽  
Gas Quenching ◽  
Spark Plasma

Spark plasma sintering (SPS) has gained recognition in the last 20 years for its rapid densification of hard-to-sinter conventional and advanced materials, including metals, ceramics, polymers, and composites. Herein, we describe the unconventional usages of the SPS technique developed in the field. The potential of various new modifications in the SPS technique, from pressureless to the integration of a novel gas quenching system to extrusion, has led to SPS’ evolution into a completely new manufacturing tool. The SPS technique’s modifications have broadened its usability from merely a densification tool to the fabrication of complex-shaped components, advanced functional materials, functionally gradient materials, interconnected materials, and porous filter materials for real-life applications. The broader application achieved by modification of the SPS technique can provide an alternative to conventional powder metallurgy methods as a scalable manufacturing process. The future challenges and opportunities in this emerging research field have also been identified and presented.

scholarly journals The Impact of COVID-19 on Hospitality Industry in Greece and Its Treasured Santorini Island

2021 ◽  
Vol 13 (14) ◽  
pp. 7906
Author(s):  
Nikola Medová ◽  
Lucie Macková ◽  
Jaromir Harmacek
Keyword(s):  
Social Impact ◽  
Tourism Sector ◽  
Challenges And Opportunities ◽  
Multiple Variables ◽  
Hospitality Sector ◽  
Tourism And Hospitality ◽  
The Impact ◽  
Further Development

This paper focuses on the dynamic of the recent upheaval in the tourism and hospitality sector due to the COVID-19 epidemic in Greece and Santorini island. It uses the case study of a country one-fourth of whose GDP consists of tourism. We compare the available statistical data showing the change in variables in the previous years with 2020 and look into the new challenges and opportunities posed by the drop in the numbers of visitors and flights. We focus mainly on the economic and social impact on the destination and possible future scenarios for further development in the area. Data show a significant effect of the pandemic on multiple variables, such as the long-term trend of the importance of tourism sector in GDP in Greece, the number of flights and visitors to Greece and Santorini island, and the contribution of tourism and travel to GDP. Based on the available data, we also construct three foresight scenarios that describe the possible futures for Santorini island in terms of the pandemic evolution. These scenarios may help various stakeholders and policymakers to be better prepared for different developments that may appear.

scholarly journals Protein ubiquitination via dehydroalanine: development and insights into the diastereoselective 1,4-addition step

2016 ◽  
Vol 14 (21) ◽  
pp. 4817-4823 ◽  
Author(s):  
Roman Meledin ◽  
Sachitanand M. Mali ◽  
Sumeet K. Singh ◽  
Ashraf Brik
Keyword(s):  
Specific Protein ◽  
Site Specific ◽  
Isopeptide Bond ◽  
Protein Ubiquitination

We report a strategy for site-specific protein ubiquitination using dehydroalanine (Dha) chemistry for the preparation of ubiquitin conjugates bearing a very close mimic of the native isopeptide bond.

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