scholarly journals Activation and Delivery of Tetrazine-Responsive Bioorthogonal Prodrugs

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5640 ◽  
Author(s):  
Yayue Wang ◽  
Chang Zhang ◽  
Haoxing Wu ◽  
Ping Feng
Keyword(s):  
Great Promise ◽  
Attractive Alternative ◽  
Bioorthogonal Chemistry ◽  
Cleavage Reaction ◽  
Trigger Factors ◽  
Temporal Precision ◽  
Bioorthogonal Reactions ◽  
Factors Associated ◽  
Spatio Temporal ◽  
Target Effects

Prodrugs, which remain inert until they are activated under appropriate conditions at the target site, have emerged as an attractive alternative to drugs that lack selectivity and show off-target effects. Prodrugs have traditionally been activated by enzymes, pH or other trigger factors associated with the disease. In recent years, bioorthogonal chemistry has allowed the creation of prodrugs that can be chemically activated with spatio-temporal precision. In particular, tetrazine-responsive bioorthogonal reactions can rapidly activate prodrugs with excellent biocompatibility. This review summarized the recent development of tetrazine bioorthogonal cleavage reaction and great promise for prodrug systems.

Elucidating cyclic AMP signaling in subcellular domains with optogenetic tools and fluorescent biosensors

2019 ◽  
Vol 47 (6) ◽  
pp. 1733-1747 ◽  
Author(s):  
Christina Klausen ◽  
Fabian Kaiser ◽  
Birthe Stüven ◽  
Jan N. Hansen ◽  
Dagmar Wachten
Keyword(s):  
Cyclic Amp ◽  
Adenosine Monophosphate ◽  
Adenylyl Cyclases ◽  
Temporal Precision ◽  
Fluorescent Biosensors ◽  
Subcellular Domains ◽  
Spatio Temporal ◽  
Hydrolysis Of ◽  
Shed Light ◽  
Cyclic Amp Signaling

The second messenger 3′,5′-cyclic nucleoside adenosine monophosphate (cAMP) plays a key role in signal transduction across prokaryotes and eukaryotes. Cyclic AMP signaling is compartmentalized into microdomains to fulfil specific functions. To define the function of cAMP within these microdomains, signaling needs to be analyzed with spatio-temporal precision. To this end, optogenetic approaches and genetically encoded fluorescent biosensors are particularly well suited. Synthesis and hydrolysis of cAMP can be directly manipulated by photoactivated adenylyl cyclases (PACs) and light-regulated phosphodiesterases (PDEs), respectively. In addition, many biosensors have been designed to spatially and temporarily resolve cAMP dynamics in the cell. This review provides an overview about optogenetic tools and biosensors to shed light on the subcellular organization of cAMP signaling.

scholarly journals VipariNama: RNA viral vectors to rapidly elucidate the relationship between gene expression and phenotype

2021 ◽  
Author(s):  
Arjun Khakhar ◽  
Cecily Wang ◽  
Ryan Swanson ◽  
Sydney Stokke ◽  
Furva Rizvi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Viral Vectors ◽  
Viral Vector ◽  
Tobacco Rattle Virus ◽  
Plant Size ◽  
Great Promise ◽  
Attractive Alternative ◽  
Gibberellin Biosynthesis ◽  
In Planta

Abstract Synthetic transcription factors have great promise as tools to help elucidate relationships between gene expression and phenotype by allowing tunable alterations of gene expression without genomic alterations of the loci being studied. However, the years-long timescales, high cost, and technical skill associated with plant transformation have limited their use. In this work we developed a technology called VipariNama (ViN) in which vectors based on the Tobacco Rattle Virus (TRV) are used to rapidly deploy Cas9-based synthetic transcription factors and reprogram gene expression in planta. We demonstrate that ViN vectors can implement activation or repression of multiple genes systemically and persistently over several weeks in Nicotiana benthamiana, Arabidopsis (Arabidopsis thaliana), and tomato (Solanum lycopersicum). By exploring strategies including RNA scaffolding, viral vector ensembles, and viral engineering, we describe how the flexibility and efficacy of regulation can be improved. We also show how this transcriptional reprogramming can create predictable changes to metabolic phenotypes, such as gibberellin biosynthesis in N. benthamiana and anthocyanin accumulation in Arabidopsis, as well as developmental phenotypes, such as plant size in N. benthamiana, Arabidopsis, and tomato. These results demonstrate how ViN vector-based reprogramming of different aspects of gibberellin signaling can be used to engineer plant size in a range of plant species in a matter of weeks. In summary, VipariNama accelerates the timeline for generating phenotypes from over a year to just a few weeks, providing an attractive alternative to transgenesis for synthetic transcription factor-enabled hypothesis testing and crop engineering.

scholarly journals VipariNama: RNA vectors to rapidly reprogram plant morphology and metabolism

2020 ◽  
Author(s):  
Arjun Khakhar ◽  
Cecily Wang ◽  
Ryan Swanson ◽  
Sydney Stokke ◽  
Furva Rizvi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Plant Morphology ◽  
Plant Size ◽  
Great Promise ◽  
Attractive Alternative ◽  
Biological Processes ◽  
In Planta ◽  
Transcriptional Reprogramming ◽  
Long Timescales

AbstractSynthetic transcription factors have great promise as tools to explore biological processes. By allowing precise alterations in gene expression, they can help elucidate relationships between gene expression and plant morphology or metabolism. However, the years-long timescales, high cost, and technical skill associated with plant transformation have dramatically slowed their use. In this work, we developed a new platform technology called VipariNama (ViN) in which RNA vectors are used to rapidly deploy synthetic transcription factors and reprogram gene expression in planta. We demonstrate how ViN vectors can direct activation or repression of multiple genes, systemically and persistently over several weeks, and in multiple plant species. We also show how this transcriptional reprogramming can create predictable changes to metabolic and morphological phenotypes in the model plants Nicotiana benthamiana and Arabidopsis thaliana in a matter of weeks. Finally, we show how a model of gibberellin signaling can guide ViN vector-based reprogramming to rapidly engineer plant size in both model species as well as the crop Solanum lycopersicum (tomato). In summary, using VipariNama accelerates the timeline for generating phenotypes from over a year to just a few weeks, providing an attractive alternative to transgenesis for synthetic transcription factor-enabled hypothesis testing and crop engineering.

CRISPR/Cas9 for cancer treatment: technology, clinical applications and challenges

2020 ◽  
Vol 19 (3) ◽  
pp. 209-214 ◽  
Author(s):  
Xing Cheng ◽  
Shaoyi Fan ◽  
Chengcai Wen ◽  
Xianfa Du
Keyword(s):  
Cancer Treatment ◽  
Viral Infections ◽  
Adaptive Immune System ◽  
Clinical Applications ◽  
Great Promise ◽  
General Function ◽  
Treatment Technology ◽  
Delivery Methods ◽  
Function Mechanism ◽  
Target Effects

Abstract Clustered regularly interspaced short palindromic repeats (CRISPR) is described as RNA mediated adaptive immune system defense, which is naturally found in bacteria and archaea. CRISPR-Cas9 has shown great promise for cancer treatment in cancer immunotherapy, manipulation of cancer genome and epigenome and elimination or inactivation of carcinogenic viral infections. However, many challenges remain to be addressed to increase its efficacy, including off-target effects, editing efficiency, fitness of edited cells, immune response and delivery methods. Here, we explain CRISPR-Cas classification and its general function mechanism for gene editing. Then, we summarize these preclinical CRISPR-Cas9-based therapeutic strategies against cancer. Moreover, the challenges and improvements of CRISPR-Cas9 clinical applications will be discussed.

scholarly journals Risk and Triggering Factors Associated with Bronchial Asthma Among School-Going Children in an Urban City of Coastal Karnataka

2017 ◽  
Vol 37 (1) ◽  
pp. 59-66
Author(s):  
Sowmini P. Kamath ◽  
Shrividya Shrishakumar ◽  
Animesh Jain ◽  
Anand Ramakrishna ◽  
Shantharam B Baliga
Keyword(s):  
Risk Factors ◽  
Statistical Significance ◽  
Cross Sectional Study ◽  
Public Health Issue ◽  
Trigger Factors ◽  
Cross Sectional ◽  
Factors Associated ◽  
Urban City ◽  
Triggering Factors ◽  
At Home

Introduction: Asthma is common in childhood and is a major public health issue. The objectives of this study were to identify risk and triggering factors associated with asthma among school children.Material and Methods: A prospective cross sectional study was conducted among 6-15 years old children, over two months in two private schools at Mangalore city. Trigger factors were assessed as per asthma trigger inventory (ATI). Responses were graded from 0-5 score based on ‘never’,’ rarely’, ‘sometimes’, ‘most of the time’ and ‘always’. A predesigned questionnaire suiting the city environment was prepared and used to assess the risk and triggering factors. Analysis was done using SPSS version 16.Results: Asthma and allergic rhinitis in parents (34.1%,40.7%), smoking at home(24.2%), exclusive breast feeding absence (27.5%),early weaning(24.2%), living in a flat (37.4%) and pets at home(37.4%) were risk factors noted. As per ATI, it was found that ‘having a cold’ was the most frequently selected trigger at 94.5% (47.3% ‘sometimes’, 2.2% ‘always’), followed by ‘running’ at 79.1% (27.5% ‘sometimes’, 13.2% ‘always’), and ‘house dust’ at 69.2% (31.9% ‘sometimes’, 6.6% ‘always’). The highest mean was for infections, (2.228, SD=0.546), followed by physical exercise (2.167, SD=0.331). Animal allergens had lowest mean (1.527, SD=0.104), followed by psychological triggers at second lowest (1.579, SD=0.181). However none of the risk and trigger factors had statistical significance with asthma.Conclusion: Avoiding exposure to probable triggers and identifying risk factors would aid in planning effective strategic measures with better quality of life.

scholarly journals Spatio-Temporal Factors Associated with Meningococcal Meningitis Annual Incidence at the Health Centre Level in Niger, 2004–2010

2014 ◽  
Vol 8 (5) ◽  
pp. e2899 ◽  
Author(s):  
Juliette Paireau ◽  
Halima B. Maïnassara ◽  
Jean-François Jusot ◽  
Jean-Marc Collard ◽  
Issa Idi ◽  
...  
Keyword(s):  
Health Centre ◽  
Meningococcal Meningitis ◽  
Annual Incidence ◽  
Factors Associated ◽  
Temporal Factors ◽  
Spatio Temporal ◽  
Health Centre Level

Nanomechanochemical Delivery of Nanoparticles for Nanomechanics Inside Living Cells

2010 ◽  
Author(s):  
Kyungsuk Yum ◽  
Sungsoo Na ◽  
Yang Xiang ◽  
Ning Wang ◽  
Min-Feng Yu
Keyword(s):  
Single Molecule ◽  
Living Cells ◽  
Endocytic Pathway ◽  
Great Promise ◽  
Biological Processes ◽  
Temporal Precision ◽  
Single Molecule Level ◽  
Cellular Processes ◽  
Cellular Environment ◽  
Biological Studies

Studying biological processes and mechanics in living cells is challenging but highly rewarding. Recent advances in experimental techniques have provided numerous ways to investigate cellular processes and mechanics of living cells. However, most of existing techniques for biomechanics are limited to experiments outside or on the membrane of cells, due to the difficulties in physically accessing the interior of living cells. On the other hand, nanomaterials, such as fluorescent quantum dots (QDs) and magnetic nanoparticles, have shown great promise to overcome such limitations due to their small sizes and excellent functionalities, including bright and stable fluorescence and remote manipulability. However, except a few systems, the use of nanoparticles has been limited to the study of biological studies on cell membranes or related to endocytosis, because of the difficulty of delivering dispersed and single nanoparticles into living cells. Various strategies have been explored, but delivered nanoparticles are often trapped in the endocytic pathway or form aggregates in the cytoplasm, limiting their further use. Here we show a nanoscale direct delivery method, named nanomechanochemical delivery, where we manipulate a nanotube-based nanoneedle, carrying “cargo” (QDs in this study), to mechanically penetrate the cell membrane, access specific areas inside cells, and release the cargo [1]. We selectively delivered well-dispersed QDs into either the cytoplasm or the nucleus of living cells. We quantified the dynamics of the delivered QDs by single-molecule tracking and demonstrated the applicability of the QDs as a nanoscale probe for studying nanomechanics inside living cells (by using the biomicrorhology method), revealing the biomechanical heterogeneity of the cellular environment. This method may allow new strategies for studying biological processes and mechanics in living cells with spatial and temporal precision, potentially at the single-molecule level.

Phonological disorders and spatio‐temporal precision of stop consonant gestures

1998 ◽  
Vol 104 (3) ◽  
pp. 1853-1853
Author(s):  
Jan Edwards ◽  
Marios Fourakis ◽  
Mary Beckman ◽  
Pauline Welby ◽  
Ying Xu
Keyword(s):  
Stop Consonant ◽  
Temporal Precision ◽  
Phonological Disorders ◽  
Spatio Temporal

scholarly journals The role of telecare in supporting the needs of elderly people

2007 ◽  
Vol 13 (6) ◽  
pp. 293-297 ◽  
Author(s):  
Simon Brownsell ◽  
Hazel Aldred ◽  
Mark S Hawley
Keyword(s):  
Literature Review ◽  
Elderly People ◽  
Expert Panel ◽  
Trigger Factors ◽  
Factors Associated ◽  
Levels Of Care ◽  
Care And Support ◽  
The Impact ◽  
Major Consideration

A literature review was conducted to identify the 'trigger factors' associated with a need for increased levels of care and support for elderly people. An expert panel then prioritized the trigger factors into one of five bands of importance. The literature review produced 2037 hits. Of these, 1768 were excluded after reading the abstract and 111 after reading the full paper, leaving 158 papers for inclusion in the review. From these papers, 102 unique factors that triggered a need for greater care and support among elderly people were identified. The expert panel ranked 36 of the trigger factors into the top three bands of importance. Subsequent analysis suggested that telecare could be used to assist, prevent or minimise the impact of some 66% of these 36 trigger factors and 75% of the top 12 factors. This suggests that telecare has a significant role to play in the support of elderly people and should be a major consideration when re-designing services.

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