scholarly journals Mass Spectrometry-Based Methodologies for Targeted and Untargeted Identification of Protein Covalent Adducts (Adductomics): Current Status and Challenges

2019 ◽  
Vol 8 (2) ◽  
pp. 9 ◽  
Author(s):  
Nunes ◽  
Charneira ◽  
Morello ◽  
Rodrigues ◽  
Pereira ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Disease Diagnosis ◽  
Quantitative Information ◽  
Current Status ◽  
Technological Advances ◽  
Wide Range ◽  
Covalent Modifications ◽  
Covalent Adducts ◽  
Pre Treatment ◽  
Protein Covalent

Protein covalent adducts formed upon exposure to reactive (mainly electrophilic) chemicals may lead to the development of a wide range of deleterious health outcomes. Therefore, the identification of protein covalent adducts constitutes a huge opportunity for a better understanding of events underlying diseases and for the development of biomarkers which may constitute effective tools for disease diagnosis/prognosis, for the application of personalized medicine approaches and for accurately assessing human exposure to chemical toxicants. The currently available mass spectrometry (MS)-based methodologies, are clearly the most suitable for the analysis of protein covalent modifications, providing accuracy, sensitivity, unbiased identification of the modified residue and conjugates along with quantitative information. However, despite the huge technological advances in MS instrumentation and bioinformatics tools, the identification of low abundant protein covalent adducts is still challenging. This review is aimed at summarizing the MS-based methodologies currently used for the identification of protein covalent adducts and the strategies developed to overcome the analytical challenges, involving not only sample pre-treatment procedures but also distinct MS and data analysis approaches.

scholarly journals Towards Building a Quantitative Proteomics Toolbox in Precision Medicine: A Mini-Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Alejandro Correa Rojo ◽  
Dries Heylen ◽  
Jan Aerts ◽  
Olivier Thas ◽  
Jef Hooyberghs ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Quantitative Proteomics ◽  
Disease Diagnosis ◽  
Clinical Diagnostics ◽  
Current Status ◽  
Proteomics Data ◽  
Treatment And Prevention ◽  
Intermediate Phenotypes ◽  
Wide Range ◽  
Indispensable Tool

Precision medicine as a framework for disease diagnosis, treatment, and prevention at the molecular level has entered clinical practice. From the start, genetics has been an indispensable tool to understand and stratify the biology of chronic and complex diseases in precision medicine. However, with the advances in biomedical and omics technologies, quantitative proteomics is emerging as a powerful technology complementing genetics. Quantitative proteomics provide insight about the dynamic behaviour of proteins as they represent intermediate phenotypes. They provide direct biological insights into physiological patterns, while genetics accounting for baseline characteristics. Additionally, it opens a wide range of applications in clinical diagnostics, treatment stratification, and drug discovery. In this mini-review, we discuss the current status of quantitative proteomics in precision medicine including the available technologies and common methods to analyze quantitative proteomics data. Furthermore, we highlight the current challenges to put quantitative proteomics into clinical settings and provide a perspective to integrate proteomics data with genomics data for future applications in precision medicine.

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.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

scholarly journals Membrane condenser as emerging technology for water recovery and gas pre-treatment: current status and perspectives

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Adele Brunetti ◽  
Francesca Macedonio ◽  
Giuseppe Barbieri ◽  
Enrico Drioli
Keyword(s):  
Current Status ◽  
Innovative Technology ◽  
Water Recovery ◽  
Treatment Unit ◽  
Treatment Stage ◽  
Treatment Technologies ◽  
Pre Treatment ◽  
And Control

Abstract The recent roadmap of SPIRE initiative includes the development of “new separation, extraction and pre-treatment technologies” as one of the “key actions” for boosting sustainability, enhancing the availability and quality of existing resources. Membrane condenser is an innovative technology that was recently investigated for the recovery of water vapor for waste gaseous streams, such as flue gas, biogas, cooling tower plumes, etc. Recently, it has been also proposed as pre-treatment unit for the reduction and control of contaminants in waste gaseous streams (SOx and NOx, VOCs, H2S, NH3, siloxanes, halides, particulates, organic pollutants). This perspective article reports recent progresses in the applications of the membrane condenser in the treatment of various gaseous streams for water recovery and contaminant control. After an overview of the operating principle, the membranes used, and the main results achieved, the work also proposes the role of this technology as pre-treatment stage to other separation technologies. The potentialities of the technology are also discussed aspiring to pave the way towards the development of an innovative technology where membrane condenser can cover a key role in redesigning the whole upgrading process.

scholarly journals Photonic Crystal Nanobeam Cavities for Nanoscale Optical Sensing: A Review

Micromachines ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 72 ◽  
Author(s):  
Da-Quan Yang ◽  
Bing Duan ◽  
Xiao Liu ◽  
Ai-Qiang Wang ◽  
Xiao-Gang Li ◽  
...  
Keyword(s):  
Photonic Crystal ◽  
Optical Waveguides ◽  
Optical Sensing ◽  
Early Stage ◽  
Disease Diagnosis ◽  
Label Free ◽  
Quality Factors ◽  
Integrated Sensor ◽  
Early Stage Disease ◽  
Wide Range

The ability to detect nanoscale objects is particular crucial for a wide range of applications, such as environmental protection, early-stage disease diagnosis and drug discovery. Photonic crystal nanobeam cavity (PCNC) sensors have attracted great attention due to high-quality factors and small-mode volumes (Q/V) and good on-chip integrability with optical waveguides/circuits. In this review, we focus on nanoscale optical sensing based on PCNC sensors, including ultrahigh figure of merit (FOM) sensing, single nanoparticle trapping, label-free molecule detection and an integrated sensor array for multiplexed sensing. We believe that the PCNC sensors featuring ultracompact footprint, high monolithic integration capability, fast response and ultrahigh sensitivity sensing ability, etc., will provide a promising platform for further developing lab-on-a-chip devices for biosensing and other functionalities.

scholarly journals Current status of vascular access in Japan—from Dialysis Access Symposium 2017

2019 ◽  
Vol 20 (1_suppl) ◽  
pp. 38-44
Author(s):  
Mizuya Fukasawa
Keyword(s):  
Vascular Access ◽  
Current Status ◽  
Good Survival ◽  
Chronic Glomerulonephritis ◽  
Dialysis Access ◽  
Dialysis Patients ◽  
Survival Prognosis ◽  
Access Methods ◽  
Number Of Patients ◽  
Wide Range

At the second Dialysis Access Symposium held in Nagoya, Japan, a proposal was made to investigate the differences in vascular access methods used in different countries. In this article, we describe the management of vascular access in Japan. The Japanese population is rapidly aging, and the proportion of elderly patients on dialysis is also increasing. There were 325,000 dialysis patients in Japan at the end of 2015, of whom 65.1% were aged 65 years or above. The number of patients with diabetic nephropathy or nephrosclerosis as the underlying condition is also increasing, whereas the number with chronic glomerulonephritis is steadily decreasing. The Japanese health insurance system enables patients to undergo medical treatment at almost no out-of-pocket cost. Percutaneous transluminal angioplasty suffers from a severe device lag compared with other countries, but although there are limitations on permitted devices, the use of those that have been authorized is covered by medical insurance. One important point that is unique to Japan is that vascular access is performed and managed by doctors involved in dialysis across a wide range of disciplines, including nephrologists, surgeons, and urologists. This may be one factor contributing to the good survival prognosis of Japanese dialysis patients.

scholarly journals Quantitative linear dichroism imaging of molecular processes in living cells made simple by open software tools

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Alexey Bondar ◽  
Olga Rybakova ◽  
Josef Melcr ◽  
Jan Dohnálek ◽  
Petro Khoroshyy ◽  
...  
Keyword(s):  
Biological Systems ◽  
Linear Dichroism ◽  
Quantitative Information ◽  
Living Cells ◽  
Software Tools ◽  
Model Systems ◽  
Membrane Properties ◽  
Polarization Microscopy ◽  
Molecular Processes ◽  
Wide Range

AbstractFluorescence-detected linear dichroism microscopy allows observing various molecular processes in living cells, as well as obtaining quantitative information on orientation of fluorescent molecules associated with cellular features. Such information can provide insights into protein structure, aid in development of genetically encoded probes, and allow determinations of lipid membrane properties. However, quantitating and interpreting linear dichroism in biological systems has been laborious and unreliable. Here we present a set of open source ImageJ-based software tools that allow fast and easy linear dichroism visualization and quantitation, as well as extraction of quantitative information on molecular orientations, even in living systems. The tools were tested on model synthetic lipid vesicles and applied to a variety of biological systems, including observations of conformational changes during G-protein signaling in living cells, using fluorescent proteins. Our results show that our tools and model systems are applicable to a wide range of molecules and polarization-resolved microscopy techniques, and represent a significant step towards making polarization microscopy a mainstream tool of biological imaging.

scholarly journals RNA-Centric Approaches to Profile the RNA–Protein Interaction Landscape on Selected RNAs

2021 ◽  
Vol 7 (1) ◽  
pp. 11 ◽  
Author(s):  
André P. Gerber
Keyword(s):  
Mass Spectrometry ◽  
Protein Interactions ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Complexes ◽  
Cell Protein ◽  
Transcriptional Regulatory Networks ◽  
Technological Advances

RNA–protein interactions frame post-transcriptional regulatory networks and modulate transcription and epigenetics. While the technological advances in RNA sequencing have significantly expanded the repertoire of RNAs, recently developed biochemical approaches combined with sensitive mass-spectrometry have revealed hundreds of previously unrecognized and potentially novel RNA-binding proteins. Nevertheless, a major challenge remains to understand how the thousands of RNA molecules and their interacting proteins assemble and control the fate of each individual RNA in a cell. Here, I review recent methodological advances to approach this problem through systematic identification of proteins that interact with particular RNAs in living cells. Thereby, a specific focus is given to in vivo approaches that involve crosslinking of RNA–protein interactions through ultraviolet irradiation or treatment of cells with chemicals, followed by capture of the RNA under study with antisense-oligonucleotides and identification of bound proteins with mass-spectrometry. Several recent studies defining interactomes of long non-coding RNAs, viral RNAs, as well as mRNAs are highlighted, and short reference is given to recent in-cell protein labeling techniques. These recent experimental improvements could open the door for broader applications and to study the remodeling of RNA–protein complexes upon different environmental cues and in disease.

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