scholarly journals Nanoparticles: Synthesis, Morphophysiological Effects, and Proteomic Responses of Crop Plants

2020 ◽  
Vol 21 (9) ◽  
pp. 3056 ◽  
Author(s):  
Zahed Hossain ◽  
Farhat Yasmeen ◽  
Setsuko Komatsu
Keyword(s):  
Protein Interactions ◽  
Hybrid Methods ◽  
Rapid Development ◽  
Underlying Mechanism ◽  
Engineered Nanoparticles ◽  
Plant Responses ◽  
Plant Interactions ◽  
Wide Range ◽  
Modern Mass ◽  
Proteomic Techniques

Plant cells are frequently challenged with a wide range of adverse environmental conditions that restrict plant growth and limit the productivity of agricultural crops. Rapid development of nanotechnology and unsystematic discharge of metal containing nanoparticles (NPs) into the environment pose a serious threat to the ecological receptors including plants. Engineered nanoparticles are synthesized by physical, chemical, biological, or hybrid methods. In addition, volcanic eruption, mechanical grinding of earthquake-generating faults in Earth’s crust, ocean spray, and ultrafine cosmic dust are the natural source of NPs in the atmosphere. Untying the nature of plant interactions with NPs is fundamental for assessing their uptake and distribution, as well as evaluating phytotoxicity. Modern mass spectrometry-based proteomic techniques allow precise identification of low abundant proteins, protein–protein interactions, and in-depth analyses of cellular signaling networks. The present review highlights current understanding of plant responses to NPs exploiting high-throughput proteomics techniques. Synthesis of NPs, their morphophysiological effects on crops, and applications of proteomic techniques, are discussed in details to comprehend the underlying mechanism of NPs stress acclimation.

Current Trends in Biotherapeutic Higher Order Structure Characterization by Irreversible Covalent Footprinting Mass Spectrometry

2019 ◽  
Vol 26 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Natalie K. Garcia ◽  
Galahad Deperalta ◽  
Aaron T. Wecksler
Keyword(s):  
Mass Spectrometry ◽  
Protein Structure ◽  
Protein Interactions ◽  
Quaternary Structure ◽  
Solvent Accessibility ◽  
Higher Order ◽  
Structure Characterization ◽  
Order Structure ◽  
Protein Footprinting ◽  
Wide Range

Background: Biotherapeutics, particularly monoclonal antibodies (mAbs), are a maturing class of drugs capable of treating a wide range of diseases. Therapeutic function and solutionstability are linked to the proper three-dimensional organization of the primary sequence into Higher Order Structure (HOS) as well as the timescales of protein motions (dynamics). Methods that directly monitor protein HOS and dynamics are important for mapping therapeutically relevant protein-protein interactions and assessing properly folded structures. Irreversible covalent protein footprinting Mass Spectrometry (MS) tools, such as site-specific amino acid labeling and hydroxyl radical footprinting are analytical techniques capable of monitoring the side chain solvent accessibility influenced by tertiary and quaternary structure. Here we discuss the methodology, examples of biotherapeutic applications, and the future directions of irreversible covalent protein footprinting MS in biotherapeutic research and development. Conclusion: Bottom-up mass spectrometry using irreversible labeling techniques provide valuable information for characterizing solution-phase protein structure. Examples range from epitope mapping and protein-ligand interactions, to probing challenging structures of membrane proteins. By paring these techniques with hydrogen-deuterium exchange, spectroscopic analysis, or static-phase structural data such as crystallography or electron microscopy, a comprehensive understanding of protein structure can be obtained.

Approach in improving potency and selectivity of kinase inhibitors: Allosteric kinase inhibitors

2020 ◽  
Vol 21 ◽  
Author(s):  
Shangfei Wei ◽  
Tianming Zhao ◽  
Jie Wang ◽  
Xin Zhai
Keyword(s):  
Protein Interactions ◽  
Kinase Inhibitors ◽  
Binding Modes ◽  
Allosteric Inhibitors ◽  
Wide Range ◽  
Allosteric Sites ◽  
Protein Functions ◽  
Regulate Protein

: Allostery is an efficient and particular regulatory mechanism to regulate protein functions. Different from conserved orthosteric sites, allosteric sites have distinctive functional mechanism to form the complex regulatory network. In drug discovery, kinase inhibitors targeting the allosteric pockets have received extensive attention for the advantages of high selectivity and low toxicity. The approval of trametinib as the first allosteric inhibitor validated that allosteric inhibitors could be used as effective therapeutic drugs for treatment of diseases. To date, a wide range of allosteric inhibitors have been identified. In this perspective, we outline different binding modes and potential advantages of allosteric inhibitors. In the meantime, the research processes of typical and novel allosteric inhibitors are described briefly in terms of structureactivity relationships, ligand-protein interactions and in vitro and in vivo activity. Additionally, challenges as well as opportunities are presented.

The Application of Multicriteria Decision Analysis Methods in Health Care: A Literature Review

2021 ◽  
pp. 0272989X2110190
Author(s):  
Ilyas Khan ◽  
Liliane Pintelon ◽  
Harry Martin
Keyword(s):  
Health Care ◽  
Decision Making ◽  
Decision Analysis ◽  
Medical Devices ◽  
Hybrid Methods ◽  
Multicriteria Decision Analysis ◽  
Multicriteria Decision ◽  
Health Care Decision ◽  
Wide Range ◽  
Care Decision

Objectives The main objectives of this article are 2-fold. First, we explore the application of multicriteria decision analysis (MCDA) methods in different areas of health care, particularly the adoption of various MCDA methods across health care decision making problems. Second, we report on the publication trends on the application of MCDA methods in health care. Method PubMed was searched for literature from 1960 to 2019 in the English language. A wide range of keywords was used to retrieve relevant studies. The literature search was performed in September 2019. Articles were included only if they have reported an MCDA case in health care. Results and Conclusion The search yielded 8,318 abstracts, of which 158 fulfilled the inclusion criteria and were considered for further analysis. Hybrid methods are the most widely used methods in health care decision making problems. When it comes to single methods, analytic hierarchy process (AHP) is the most widely used method followed by TOPSIS (technique for order preference by similarity to ideal solution), multiattribute utility theory, goal programming, EVIDEM (evidence and value: impact on decision making), evidential reasoning, discrete choice experiment, and so on. Interestingly, the usage of hybrid methods has been high in recent years. AHP is most widely applied in screening and diagnosing and followed by treatment, medical devices, resource allocation, and so on. Furthermore, treatment, screening and diagnosing, medical devices, and drug development and assessment got more attention in the MCDA context. It is indicated that the application of MCDA methods to health care decision making problem is determined by the nature and complexity of the health care problem. However, guidelines and tools exist that assist in the selection of an MCDA method.

scholarly journals Ways into Understanding HIF Inhibition

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 159
Author(s):  
Tina Schönberger ◽  
Joachim Fandrey ◽  
Katrin Prost-Fingerle
Keyword(s):  
Protein Interactions ◽  
Target Genes ◽  
Protein Protein Interactions ◽  
Low Oxygen ◽  
Drug Candidates ◽  
Open Questions ◽  
Wide Range ◽  
Hif Pathway

Hypoxia is a key characteristic of tumor tissue. Cancer cells adapt to low oxygen by activating hypoxia-inducible factors (HIFs), ensuring their survival and continued growth despite this hostile environment. Therefore, the inhibition of HIFs and their target genes is a promising and emerging field of cancer research. Several drug candidates target protein–protein interactions or transcription mechanisms of the HIF pathway in order to interfere with activation of this pathway, which is deregulated in a wide range of solid and liquid cancers. Although some inhibitors are already in clinical trials, open questions remain with respect to their modes of action. New imaging technologies using luminescent and fluorescent methods or nanobodies to complement widely used approaches such as chromatin immunoprecipitation may help to answer some of these questions. In this review, we aim to summarize current inhibitor classes targeting the HIF pathway and to provide an overview of in vitro and in vivo techniques that could improve the understanding of inhibitor mechanisms. Unravelling the distinct principles regarding how inhibitors work is an indispensable step for efficient clinical applications and safety of anticancer compounds.

scholarly journals High-Throughput Phenotyping Methods for Breeding Drought-Tolerant Crops

2021 ◽  
Vol 22 (15) ◽  
pp. 8266
Author(s):  
Minsu Kim ◽  
Chaewon Lee ◽  
Subin Hong ◽  
Song Lim Kim ◽  
Jeong-Ho Baek ◽  
...  
Keyword(s):  
Drought Stress ◽  
High Throughput ◽  
Large Scale ◽  
Crop Yields ◽  
Plant Traits ◽  
Rapid Development ◽  
Plant Responses ◽  
Phenotypic Data ◽  
Agricultural Technologies ◽  
High Throughput Phenotyping

Drought is a main factor limiting crop yields. Modern agricultural technologies such as irrigation systems, ground mulching, and rainwater storage can prevent drought, but these are only temporary solutions. Understanding the physiological, biochemical, and molecular reactions of plants to drought stress is therefore urgent. The recent rapid development of genomics tools has led to an increasing interest in phenomics, i.e., the study of phenotypic plant traits. Among phenomic strategies, high-throughput phenotyping (HTP) is attracting increasing attention as a way to address the bottlenecks of genomic and phenomic studies. HTP provides researchers a non-destructive and non-invasive method yet accurate in analyzing large-scale phenotypic data. This review describes plant responses to drought stress and introduces HTP methods that can detect changes in plant phenotypes in response to drought.

scholarly journals Advanced Functional Materials Based on Nanocellulose for Pharmaceutical/Medical Applications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1125
Author(s):  
Raluca Nicu ◽  
Florin Ciolacu ◽  
Diana E. Ciolacu
Keyword(s):  
Rapid Development ◽  
Cellulose Nanofibrils ◽  
Functional Materials ◽  
Medical Applications ◽  
Bacterial Nanocellulose ◽  
Green Materials ◽  
Wide Range ◽  
In Vivo Cytotoxicity

Nanocelluloses (NCs), with their remarkable characteristics, have proven to be one of the most promising “green” materials of our times and have received special attention from researchers in nanomaterials. A diversity of new functional materials with a wide range of biomedical applications has been designed based on the most desirable properties of NCs, such as biocompatibility, biodegradability, and their special physicochemical properties. In this context and under the pressure of rapid development of this field, it is imperative to synthesize the successes and the new requirements in a comprehensive review. The first part of this work provides a brief review of the characteristics of the NCs (cellulose nanocrystals—CNC, cellulose nanofibrils—CNF, and bacterial nanocellulose—BNC), as well as of the main functional materials based on NCs (hydrogels, nanogels, and nanocomposites). The second part presents an extensive review of research over the past five years on promising pharmaceutical and medical applications of nanocellulose-based materials, which have been discussed in three important areas: drug-delivery systems, materials for wound-healing applications, as well as tissue engineering. Finally, an in-depth assessment of the in vitro and in vivo cytotoxicity of NCs-based materials, as well as the challenges related to their biodegradability, is performed.

scholarly journals Single and Double Infections with Wolbachia in the Parasitic Wasp Nasonia vitripennis Effects on Compatibility

Genetics ◽  
1996 ◽  
Vol 143 (2) ◽  
pp. 961-972 ◽  
Author(s):  
Marie-Jeanne Perrot-Minnot ◽  
Li Rong Guo ◽  
John H Werren
Keyword(s):  
Genomic Dna ◽  
Rapid Development ◽  
Parasitic Wasp ◽  
Pcr Amplification ◽  
Bacterial Strains ◽  
Nasonia Vitripennis ◽  
Larval Diapause ◽  
Wide Range ◽  
Reproductive Incompatibility ◽  
Infected Line

Abstract Wolbachia are cytoplasmically inherited bacteria responsible for reproductive incompatibility in a wide range of insects. There has been little exploration, however, of within species Wolbachia polymorphisms and their effects on compatibility. Here we show that some strains of the parasitic wasp Nasonia vitripennis are infected with two distinct bacterial strains (A and B) whereas others are singly infected (A or B). Double and single infections are confirmed by both PCR amplification and Southern analysis of genomic DNA. Furthermore, it is shown that prolonged larval diapause (the overwintering stage of the wasp) of a double-infected strain can lead to stochastic loss of one or both bacterial strains. After diapause of a double-infected line, sublines were produced with AB, A only, B only or no Wolbachia. A and B sublines are bidirectionally incompatible, whereas males from AB lines are unidirectionally incompatible with females of A and B sublines. Results therefore show rapid development of bidirectional incompatibility within a species due to segregation of associated symbiotic bacteria.

scholarly journals Ozone damage, detoxification and the role of isoprenoids – new impetus for integrated models

2016 ◽  
Vol 43 (4) ◽  
pp. 324 ◽  
Author(s):  
Supriya Tiwari ◽  
Rüdiger Grote ◽  
Galina Churkina ◽  
Tim Butler
Keyword(s):  
Stomatal Conductance ◽  
Environmental Conditions ◽  
Economic Losses ◽  
Plant Responses ◽  
Damage Scenarios ◽  
Biochemical Processes ◽  
Wide Range ◽  
Defence Responses ◽  
High Concentrations ◽  
The Impact

High concentrations of ozone (O3) can have significant impacts on the health and productivity of agricultural and forest ecosystems, leading to significant economic losses. In order to estimate this impact under a wide range of environmental conditions, the mechanisms of O3 impacts on physiological and biochemical processes have been intensively investigated. This includes the impact on stomatal conductance, the formation of reactive oxygen species and their effects on enzymes and membranes, as well as several induced and constitutive defence responses. This review summarises these processes, discusses their importance for O3 damage scenarios and assesses to which degree this knowledge is currently used in ecosystem models which are applied for impact analyses. We found that even in highly sophisticated models, feedbacks affecting regulation, detoxification capacity and vulnerability are generally not considered. This implies that O3 inflicted alterations in carbon and water balances cannot be sufficiently well described to cover immediate plant responses under changing environmental conditions. Therefore, we suggest conceptual models that link the depicted feedbacks to available process-based descriptions of stomatal conductance, photosynthesis and isoprenoid formation, particularly the linkage to isoprenoid models opens up new options for describing biosphere-atmosphere interactions.

scholarly journals High-Throughput Quantitative Assay Technologies for Accelerating the Discovery and Optimization of Targeted Protein Degradation Therapeutics

2021 ◽  
pp. 247255522098504
Author(s):  
Jeffrey R. Simard ◽  
Linda Lee ◽  
Ellen Vieux ◽  
Reina Improgo ◽  
Trang Tieu ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Protein Degradation ◽  
Protein Interactions ◽  
Fluorescent Protein ◽  
De Novo ◽  
Rapid Development ◽  
Dependent Manner ◽  
Western Blots ◽  
Advantages And Disadvantages ◽  
Degradation Rates

The aberrant regulation of protein expression and function can drastically alter cellular physiology and lead to numerous pathophysiological conditions such as cancer, inflammatory diseases, and neurodegeneration. The steady-state expression levels of endogenous proteins are controlled by a balance of de novo synthesis rates and degradation rates. Moreover, the levels of activated proteins in signaling cascades can be further modulated by a variety of posttranslational modifications and protein–protein interactions. The field of targeted protein degradation is an emerging area for drug discovery in which small molecules are used to recruit E3 ubiquitin ligases to catalyze the ubiquitination and subsequent degradation of disease-causing target proteins by the proteasome in both a dose- and time-dependent manner. Traditional approaches for quantifying protein level changes in cells, such as Western blots, are typically low throughput with limited quantification, making it hard to drive the rapid development of therapeutics that induce selective, rapid, and sustained protein degradation. In the last decade, a number of techniques and technologies have emerged that have helped to accelerate targeted protein degradation drug discovery efforts, including the use of fluorescent protein fusions and reporter tags, flow cytometry, time-resolved fluorescence energy transfer (TR-FRET), and split luciferase systems. Here we discuss the advantages and disadvantages associated with these technologies and their application to the development and optimization of degraders as therapeutics.

scholarly journals Multiple cellular compartments engagement in Nicotiana benthamiana-peanut stunt virus-satRNA interactions revealed by systems biology approach

2021 ◽  
Author(s):  
Barbara Wrzesińska ◽  
Agnieszka Zmienko ◽  
Lam Dai Vu ◽  
Ive De Smet ◽  
Aleksandra Obrępalska-Stęplowska
Keyword(s):  
Virus Infection ◽  
Nicotiana Benthamiana ◽  
Cellular Localization ◽  
Plant Interactions ◽  
Satellite Rna ◽  
Functional Connections ◽  
Cell Compartments ◽  
Wide Range ◽  
Peanut Stunt Virus ◽  
Cellular Compartments

Abstract Key message PSV infection changed the abundance of host plant’s transcripts and proteins associated with various cellular compartments, including ribosomes, chloroplasts, mitochondria, the nucleus and cytosol, affecting photosynthesis, translation, transcription, and splicing. Abstract Virus infection is a process resulting in numerous molecular, cellular, and physiological changes, a wide range of which can be analyzed due to development of many high-throughput techniques. Plant RNA viruses are known to replicate in the cytoplasm; however, the roles of chloroplasts and other cellular structures in the viral replication cycle and in plant antiviral defense have been recently emphasized. Therefore, the aim of this study was to analyze the small RNAs, transcripts, proteins, and phosphoproteins affected during peanut stunt virus strain P (PSV-P)–Nicotiana benthamiana interactions with or without satellite RNA (satRNA) in the context of their cellular localization or functional connections with particular cellular compartments to elucidate the compartments most affected during pathogenesis at the early stages of infection. Moreover, the processes associated with particular cell compartments were determined. The ‘omic’ results were subjected to comparative data analyses. Transcriptomic and small RNA (sRNA)–seq data were obtained to provide new insights into PSV-P–satRNA–plant interactions, whereas previously obtained proteomic and phosphoproteomic data were used to broaden the analysis to terms associated with cellular compartments affected by virus infection. Based on the collected results, infection with PSV-P contributed to changes in the abundance of transcripts and proteins associated with various cellular compartments, including ribosomes, chloroplasts, mitochondria, the nucleus and the cytosol, and the most affected processes were photosynthesis, translation, transcription, and mRNA splicing. Furthermore, sRNA-seq and phosphoproteomic analyses indicated that kinase regulation resulted in decreases in phosphorylation levels. The kinases were associated with the membrane, cytoplasm, and nucleus components.

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