scholarly journals Recent Developments Toward Integrated Metabolomics Technologies (UHPLC-MS-SPE-NMR and MicroED) for Higher-Throughput Confident Metabolite Identifications

2021 ◽  
Vol 8 ◽  
Author(s):  
Rajarshi Ghosh ◽  
Guanhong Bu ◽  
Brent L. Nannenga ◽  
Lloyd W. Sumner
Keyword(s):  
Small Molecule ◽  
Structure Elucidation ◽  
Large Scale ◽  
Metabolite Identification ◽  
Spectral Features ◽  
Instrumental Ensemble ◽  
Analytical Instruments ◽  
Methods Development ◽  
Structure Determinations ◽  
Recent Developments

Metabolomics has emerged as a powerful discipline to study complex biological systems from a small molecule perspective. The success of metabolomics hinges upon reliable annotations of spectral features obtained from MS and/or NMR. In spite of tremendous progress with regards to analytical instrumentation and computational tools, < 20% of spectral features are confidently identified in most untargeted metabolomics experiments. This article explores the integration of multiple analytical instruments such as UHPLC-MS/MS-SPE-NMR and the cryo-EM method MicroED to achieve large-scale and confident metabolite identifications in a higher-throughput manner. UHPLC-MS/MS-SPE allows for the simultaneous automated purification of metabolites followed by offline structure elucidation and structure validation by NMR and MicroED. Large-scale study of complex metabolomes such as that of the model plant legume Medicago truncatula can be achieved using an integrated UHPLC-MS/MS-SPE-NMR metabolomics platform. Additionally, recent developments in MicroED to study structures of small organic molecules have enabled faster, easier and precise structure determinations of metabolites. A MicroED small molecule structure elucidation workflow (e.g., crystal screening, sample preparation, data collection and data processing/structure determination) has been described. Ongoing MicroED methods development and its future scope related to structure elucidation of specialized metabolites and metabolomics are highlighted. The incorporation of MicroED with a UHPLC-MS/MS-SPE-NMR instrumental ensemble offers the potential to accelerate and achieve higher rates of metabolite identification.

Recent Developments in the Downstream Processing of Phycobiliproteins from Algae: A Review

2021 ◽  
Vol 06 ◽  
Author(s):  
Ayekpam Chandralekha Devi ◽  
G. K. Hamsavi ◽  
Simran Sahota ◽  
Rochak Mittal ◽  
Hrishikesh A. Tavanandi ◽  
...  
Keyword(s):  
Cell Wall ◽  
Large Scale ◽  
Downstream Processing ◽  
Review Article ◽  
Current Status ◽  
Wall Structure ◽  
Scale Production ◽  
Cell Wall Disruption ◽  
Recent Developments ◽  
Macro Algae

Abstract: Algae (both micro and macro) have gained huge attention in the recent past for their high commercial value products. They are the source of various biomolecules of commercial applications ranging from nutraceuticals to fuels. Phycobiliproteins are one such high value low volume compounds which are mainly obtained from micro and macro algae. In order to tap the bioresource, a significant amount of work has been carried out for large scale production of algal biomass. However, work on downstream processing aspects of phycobiliproteins (PBPs) from algae is scarce, especially in case of macroalgae. There are several difficulties in cell wall disruption of both micro and macro algae because of their cell wall structure and compositions. At the same time, there are several challenges in the purification of phycobiliproteins. The current review article focuses on the recent developments in downstream processing of phycobiliproteins (mainly phycocyanins and phycoerythrins) from micro and macroalgae. The current status, the recent advancements and potential technologies (that are under development) are summarised in this review article besides providing future directions for the present research area.

scholarly journals On the geophysical processes impacting palaeo-sea-level observations

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Yusuke Yokoyama ◽  
Anthony Purcell
Keyword(s):  
Sea Level ◽  
Large Scale ◽  
Global Climate ◽  
Sea Level Change ◽  
Sea Level Changes ◽  
Factors Affecting ◽  
Ice Volume ◽  
Level Change ◽  
Recent Developments ◽  
Geophysical Processes

AbstractPast sea-level change represents the large-scale state of global climate, reflecting the waxing and waning of global ice sheets and the corresponding effect on ocean volume. Recent developments in sampling and analytical methods enable us to more precisely reconstruct past sea-level changes using geological indicators dated by radiometric methods. However, ice-volume changes alone cannot wholly account for these observations of local, relative sea-level change because of various geophysical factors including glacio-hydro-isostatic adjustments (GIA). The mechanisms behind GIA cannot be ignored when reconstructing global ice volume, yet they remain poorly understood within the general sea-level community. In this paper, various geophysical factors affecting sea-level observations are discussed and the details and impacts of these processes on estimates of past ice volumes are introduced.

scholarly journals STEM-20. A CANCER STEM CELL-SELECTIVE APOPTOSIS-INDUCING SMALL MOLECULE FOR THE TREATMENT OF GBM

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii200-ii200
Author(s):  
Stephen Skirboll ◽  
Natasha Lucki ◽  
Genaro Villa ◽  
Naja Vergani ◽  
Michael Bollong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Small Molecules ◽  
Small Molecule ◽  
Large Scale ◽  
Critical Role ◽  
Tumor Formation ◽  
Cell Type ◽  
Caspase 1 ◽  
Activation Assay

Abstract INTRODUCTION Glioblastoma multiforme (GBM) is the most aggressive form of primary brain cancer. A subpopulation of multipotent cells termed GBM cancer stem cells (CSCs) play a critical role in tumor initiation and maintenance, drug resistance, and recurrence following surgery. New therapeutic strategies for the treatment of GBM have recently focused on targeting CSCs. Here we have used an unbiased large-scale screening approach to identify drug-like small molecules that induce apoptosis in GBM CSCs in a cell type-selective manner. METHODS A luciferase-based survival assay of patient-derived GBM CSC lines was established to perform a large-scale screen of ∼one million drug-like small molecules with the goal of identifying novel compounds that are selectively toxic to chemoresistant GBM CSCs. Compounds found to kill GBM CSC lines as compared to control cell types were further characterized. A caspase activation assay was used to evaluate the mechanism of induced cell death. A xenograft animal model using patient-derived GBM CSCs was employed to test the leading candidate for suppression of in vivo tumor formation. RESULTS We identified a small molecule, termed RIPGBM, from the cell-based chemical screen that induces apoptosis in primary patient-derived GBM CSC cultures. The cell type-dependent selectivity of RIPGBM appears to arise at least in part from redox-dependent formation of a proapoptotic derivative, termed cRIPGBM, in GBM CSCs. cRIPGBM induces caspase 1-dependent apoptosis by binding to receptor-interacting protein kinase 2 (RIPK2) and acting as a molecular switch, which reduces the formation of a prosurvival RIPK2/TAK1 complex and increases the formation of a proapoptotic RIPK2/caspase 1 complex. In an intracranial GBM xenograft mouse model, RIPGBM was found to significantly suppress tumor formation. CONCLUSIONS Our chemical genetics-based approach has identified a small molecule drug candidate and a potential drug target that selectively targets cancer stem cells and provides an approach for the treatment of GBMs.

scholarly journals Metal Nanoparticle and Quantum Dot Tags for Signal Amplification in Electrochemical Immunosensors for Biomarker Detection

Chemosensors ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 85
Author(s):  
Anton Popov ◽  
Benediktas Brasiunas ◽  
Asta Kausaite-Minkstimiene ◽  
Almira Ramanaviciene
Keyword(s):  
Signal Amplification ◽  
Electrochemical Immunosensor ◽  
Metal Nanoparticle ◽  
Biomarker Detection ◽  
Analytical Instruments ◽  
Electrochemical Immunosensors ◽  
Highly Sensitive ◽  
Recent Developments ◽  
Electrochemical Signal ◽  
Detection Of Biomarkers

With the increasing importance of healthcare and clinical diagnosis, as well as the growing demand for highly sensitive analytical instruments, immunosensors have received considerable attention. In this review, electrochemical immunosensor signal amplification strategies using metal nanoparticles (MNPs) and quantum dots (Qdots) as tags are overviewed, focusing on recent developments in the ultrasensitive detection of biomarkers. MNPs and Qdots can be used separately or in combination with other nanostructures, while performing the function of nanocarriers, electroactive labels, or catalysts. Thus, different functions of MNPs and Qdots as well as recent advances in electrochemical signal amplification are discussed. Additionally, the methods most often used for antibody immobilization on nanoparticles, immunoassay formats, and electrochemical methods for indirect biomarker detection are overviewed.

scholarly journals Advances in the automated synthesis of 6-[18F]Fluoro-L-DOPA

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ângela C. B. Neves ◽  
Ivanna Hrynchak ◽  
Inês Fonseca ◽  
Vítor H. P. Alves ◽  
Mariette M. Pereira ◽  
...  
Keyword(s):  
Large Scale ◽  
Neuroendocrine Tumours ◽  
Radiochemical Yield ◽  
Clinical Applications ◽  
Clinical Use ◽  
Molar Activity ◽  
Neuropsychiatric Diseases ◽  
Recent Developments ◽  
Key Issues ◽  
Improved Methods

AbstractThe neurotracer 6-[18F] FDOPA has been, for many years, a powerful tool in PET imaging of neuropsychiatric diseases, movement disorders and brain malignancies. More recently, it also demonstrated good results in the diagnosis of other malignancies such as neuroendocrine tumours, pheochromocytoma or pancreatic adenocarcinoma.The multiple clinical applications of this tracer fostered a very strong interest in the development of new and improved methods for its radiosynthesis. The no-carrier-added nucleophilic 18F-fluorination process has gained increasing attention, in recent years, due to the high molar activities obtained, when compared with the other methods although the radiochemical yield remains low (17–30%). This led to the development of several nucleophilic synthetic processes in order to obtain the product with molar activity, radiochemical yield and enantiomeric purity suitable for human PET studies.Automation of the synthetic processes is crucial for routine clinical use and compliance with GMP requirements. Nevertheless, the complexity of the synthesis makes the production challenging, increasing the chance of failure in routine production. Thus, for large-scale clinical application and wider use of this radiopharmaceutical, progress in the automation of this complex radiosynthesis is of critical importance.This review summarizes the most recent developments of 6-[18F]FDOPA radiosynthesis and discusses the key issues regarding its automation for routine clinical use.

Approaches to the Synthesis of Lincosamine, a Derived Portion of the Antibiotic Lincomycin

1990 ◽  
Vol 43 (10) ◽  
pp. 1657 ◽  
Author(s):  
LM Engelhardt ◽  
BW Skelton ◽  
RV Stick ◽  
DMG Tilbrook ◽  
AH White
Keyword(s):  
Nitrogen Atom ◽  
Single Crystal ◽  
Structure Elucidation ◽  
X Ray ◽  
Structure Determinations

A variety of approaches towards the synthesis of lincosamine, a derived portion of the antibiotic lincomycin , are reported. Initial approaches involved the intramolecular delivery of a nitrogen atom ( trichloroacetimidate , trichloroacetylcarbamate , carbamate, 2-amino-2- phenylacetate ) attached to O4 onto C6 of a 6,7-anhydrooctoside. Later approaches, albeit more direct but again largely unsuccessful, involved the Sharpless titanium(IV)-mediated nucleophilic opening of a suitable 6,7-anhydrooctose, and the Sharpless oxyamination and the aziridination of suitable octenoses . As an aid to the structure elucidation of several compounds encountered in this work, single-crystal X-ray structure determinations are reported for methyl 6,7-anhydro-2,3-di-O-benzyl-8-deoxy-α-D-threo-D-galacto-octopyranoside , methyl 6,7-anhydro-2,3-di-O-benzyl-8-deoxy-α-D-threo-D-gluco-octopyranoside and 7-azido-7-deoxy-1,2:3,4-di-O-isopropylidene-β-L-erythro-Dgalacto-octose.

A Review of Machine Learning and Data Mining Approaches for Business Applications in Social Networks

2013 ◽  
Vol 9 (1) ◽  
pp. 36-53
Author(s):  
Evis Trandafili ◽  
Marenglen Biba
Keyword(s):  
Machine Learning ◽  
Data Mining ◽  
Social Networks ◽  
Large Scale ◽  
Viral Marketing ◽  
Social Network Mining ◽  
Business Applications ◽  
Mining Community ◽  
Recent Developments ◽  
Analysis Of Social Networks

Social networks have an outstanding marketing value and developing data mining methods for viral marketing is a hot topic in the research community. However, most social networks remain impossible to be fully analyzed and understood due to prohibiting sizes and the incapability of traditional machine learning and data mining approaches to deal with the new dimension in the learning process related to the large-scale environment where the data are produced. On one hand, the birth and evolution of such networks has posed outstanding challenges for the learning and mining community, and on the other has opened the possibility for very powerful business applications. However, little understanding exists regarding these business applications and the potential of social network mining to boost marketing. This paper presents a review of the most important state-of-the-art approaches in the machine learning and data mining community regarding analysis of social networks and their business applications. The authors review the problems related to social networks and describe the recent developments in the area discussing important achievements in the analysis of social networks and outlining future work. The focus of the review in not only on the technical aspects of the learning and mining approaches applied to social networks but also on the business potentials of such methods.

scholarly journals Enabling Large-Scale Design, Synthesis and Validation of Small Molecule Protein-Protein Antagonists

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e32839 ◽  
Author(s):  
David Koes ◽  
Kareem Khoury ◽  
Yijun Huang ◽  
Wei Wang ◽  
Michal Bista ◽  
...  
Keyword(s):  
Small Molecule ◽  
Large Scale ◽  
Design Synthesis ◽  
Scale Design
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