scholarly journals The “Green” FMOs: Diversity, Functionality and Application of Plant Flavoproteins

Catalysts ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 329 ◽  
Author(s):  
Sara Thodberg ◽  
Elizabeth H. Jakobsen Neilson
Keyword(s):  
Oxygen Atom ◽  
Small Molecules ◽  
Functional Characterization ◽  
Xenobiotic Metabolism ◽  
Pathogen Resistance ◽  
Future Research ◽  
Plant Metabolism ◽  
Hormone Metabolism ◽  
Characterization Studies ◽  
Multicellular Organisms

Flavin-dependent monooxygenases (FMOs) are ancient enzymes present in all kingdoms of life. FMOs typically catalyze the incorporation of an oxygen atom from molecular oxygen into small molecules. To date, the majority of functional characterization studies have been performed on mammalian, fungal and bacterial FMOs, showing that they play fundamental roles in drug and xenobiotic metabolism. By contrast, our understanding of FMOs across the plant kingdom is very limited, despite plants possessing far greater FMO diversity compared to both bacteria and other multicellular organisms. Here, we review the progress of plant FMO research, with a focus on FMO diversity and functionality. Significantly, of the FMOs characterized to date, they all perform oxygenation reactions that are crucial steps within hormone metabolism, pathogen resistance, signaling and chemical defense. This demonstrates the fundamental role FMOs have within plant metabolism, and presents significant opportunities for future research pursuits and downstream applications.

scholarly journals Mitochondrial redox systems as central hubs in plant metabolism and signalling

2021 ◽  
Author(s):  
Olivier Van Aken
Keyword(s):  
Stress Responses ◽  
Plant Mitochondria ◽  
Nuclear Gene ◽  
Tca Cycle ◽  
Cellular Damage ◽  
Future Research ◽  
Antioxidant Systems ◽  
Plant Metabolism ◽  
Redox Systems ◽  
Glutathione Cycle

Abstract Plant mitochondria are indispensable for plant metabolism and are tightly integrated into cellular homeostasis. This review provides an update on the latest research concerning the organisation and operation of plant mitochondrial redox systems, and how they affect cellular metabolism and signalling, plant development and stress responses. New insights into the organisation and operation of mitochondrial energy systems such as the tricarboxylic acid (TCA) cycle and mitochondrial electron chain (mtETC) are discussed. The mtETC produces reactive oxygen and nitrogen species, which can act as signals or lead to cellular damage, and are thus efficiently removed by mitochondrial antioxidant systems, including Mn-superoxide dismutase, ascorbate-glutathione cycle and thioredoxin-dependent peroxidases. Plant mitochondria are tightly connected with photosynthesis, photorespiration and cytosolic metabolism, thereby providing redox-balancing. Mitochondrial proteins are targets of extensive post-translational modifications, but their functional significance and how they are added or removed remains unclear. To operate in sync with the whole cell, mitochondria can communicate their functional status via mitochondrial retrograde signalling to change nuclear gene expression, and several recent breakthroughs here are discussed. At a whole organism level, plant mitochondria thus play crucial roles from the first minutes after seed imbibition, supporting meristem activity, growth and fertility, until senescence of darkened and aged tissue. Finally, plant mitochondria are tightly integrated with cellular and organismal responses to environmental challenges such as drought, salinity, heat and submergence, but also threats posed by pathogens. Both the major recent advances and outstanding questions are reviewed, which may help future research efforts on plant mitochondria.

scholarly journals G-Quadruplex-Based Drug Delivery Systems for Cancer Therapy

2021 ◽  
Vol 14 (7) ◽  
pp. 671
Author(s):  
Jéssica Lopes-Nunes ◽  
Paula Oliveira ◽  
Carla Cruz
Keyword(s):  
Drug Delivery ◽  
Small Molecules ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Nano Particles ◽  
Future Research ◽  
High Affinity ◽  
Dna And Rna ◽  
G Quadruplex ◽  
Gold Nano Particles

G-quadruplexes (G4s) are a class of nucleic acids (DNA and RNA) with single-stranded G-rich sequences. Owing to the selectivity of some G4s, they are emerging as targeting agents to overtake side effects of several potential anticancer drugs, and delivery systems of small molecules to malignant cells, through their high affinity or complementarity to specific targets. Moreover, different systems are being used to improve their potential, such as gold nano-particles or liposomes. Thus, the present review provides relevant data about the different studies with G4s as drug delivery systems and the challenges that must be overcome in the future research.

scholarly journals The CBL–CIPK Pathway in Plant Response to Stress Signals

2020 ◽  
Vol 21 (16) ◽  
pp. 5668
Author(s):  
Xiao Ma ◽  
Quan-Hui Li ◽  
Ya-Nan Yu ◽  
Yi-Ming Qiao ◽  
Saeed ul Haq ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Future Research ◽  
Complex Environments ◽  
Yield Improvement ◽  
Interacting Protein ◽  
Secondary Messenger ◽  
Calcineurin B ◽  
Response To Stress ◽  
Stress Signals

Plants need to cope with multitudes of stimuli throughout their lifecycles in their complex environments. Calcium acts as a ubiquitous secondary messenger in response to numerous stresses and developmental processes in plants. The major Ca2+ sensors, calcineurin B-like proteins (CBLs), interact with CBL-interacting protein kinases (CIPKs) to form a CBL–CIPK signaling network, which functions as a key component in the regulation of multiple stimuli or signals in plants. In this review, we describe the conserved structure of CBLs and CIPKs, characterize the features of classification and localization, draw conclusions about the currently known mechanisms, with a focus on novel findings in response to multiple stresses, and summarize the physiological functions of the CBL–CIPK network. Moreover, based on the gradually clarified mechanisms of the CBL–CIPK complex, we discuss the present limitations and potential prospects for future research. These aspects may provide a deeper understanding and functional characterization of the CBL–CIPK pathway and other signaling pathways under different stresses, which could promote crop yield improvement via biotechnological intervention.

Small-Molecule Immuno-Oncology Therapy: Advances, Challenges and New Directions

2019 ◽  
Vol 19 (3) ◽  
pp. 180-185 ◽  
Author(s):  
Shulun Chen ◽  
Zilan Song ◽  
Ao Zhang
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Future Research ◽  
Checkpoint Proteins ◽  
Adaptive Immune ◽  
Superior Efficacy ◽  
Adaptive Immune Cells ◽  
New Directions ◽  
Clinical Responses ◽  
Remarkable Progress

Oncology immunotherapy has gained significant advances in recent years and benefits cancer patients with superior efficacy and superior clinical responses. Currently over ten immune checkpoint antibodies targeting CTLA-4 and PD-1/PD-L1 have received regulatory approval worldwide and over thousands are under active clinical trials. However, compared to the rapid advance of Monoclonal Antibody (mAb), studies on immunotherapeutic small molecules have far lagged behind. Small molecule immunotherapy not only can target immunosuppressive mechanisms similar to mAbs, but also can stimulate intracellular pathways downstream of checkpoint proteins in innate or adaptive immune cells that mAbs are unable to access. Therefore, small molecule immunotherapy can provide an alternative treatment modality either alone or complementary to or synergistic with extracellular checkpoint mAbs to address low clinical response and drug resistance. Fortunately, remarkable progress has achieved recently in the pursuit of small molecule immunotherapy. This review intends to provide a timely highlight on those clinically investigated small molecules targeting PD-1/PD-L1, IDO1, and STING. The most advanced IDO1 inhibitor epacadostat have been aggressively progressed into multiple clinical testings. Small molecule PD-1/PD-L1 inhibitors and STING activators are still in a premature state and their decisive application needs to wait for the ongoing clinical outcomes. Since no small molecule immunotherapy has been approved yet, the future research should continue to focus on discovery of novel small molecules with distinct chemo-types and higher potency, identification of biomarkers to precisely stratify patients, as well as validation of many other immune-therapeutic targets, such as LAG3, KIRs, TIM-3, VISTA, B7-H3, and TIGIT.

scholarly journals Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN

Science ◽  
2018 ◽  
Vol 362 (6414) ◽  
pp. eaat0572 ◽  
Author(s):  
Quinlan L. Sievers ◽  
Georg Petzold ◽  
Richard D. Bunker ◽  
Aline Renneville ◽  
Mikołaj Słabicki ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Small Molecules ◽  
Zinc Finger ◽  
Ubiquitin Ligase ◽  
Biochemical Analysis ◽  
Zinc Fingers ◽  
Functional Characterization ◽  
C2h2 Zinc Finger

The small molecules thalidomide, lenalidomide, and pomalidomide induce the ubiquitination and proteasomal degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) by recruiting a Cys2-His2 (C2H2) zinc finger domain to Cereblon (CRBN), the substrate receptor of the CRL4CRBN E3 ubiquitin ligase. We screened the human C2H2 zinc finger proteome for degradation in the presence of thalidomide analogs, identifying 11 zinc finger degrons. Structural and functional characterization of the C2H2 zinc finger degrons demonstrates how diverse zinc finger domains bind the permissive drug-CRBN interface. Computational zinc finger docking and biochemical analysis predict that more than 150 zinc fingers bind the drug-CRBN complex in vitro, and we show that selective zinc finger degradation can be achieved through compound modifications. Our results provide a rationale for therapeutically targeting transcription factors that were previously considered undruggable.

scholarly journals The First Molecular Characterization of Serbian SARS-CoV-2 Isolates From a Unique Early Second Wave in Europe

2021 ◽  
Vol 12 ◽  
Author(s):  
Danijela Miljanovic ◽  
Ognjen Milicevic ◽  
Ana Loncar ◽  
Dzihan Abazovic ◽  
Dragana Despot ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Early Summer ◽  
Future Research ◽  
Viral Genomes ◽  
Rare Mutations ◽  
Second Wave ◽  
Genome Variants ◽  
Local Transmission

March 6, 2020 is considered as the official date of the beginning of the COVID-19 epidemic in Serbia. In late spring and early summer 2020, Europe recorded a decline in the rate of SARS-CoV-2 infection and subsiding of the first wave. This trend lasted until the fall, when the second wave of the epidemic began to appear. Unlike the rest of Europe, Serbia was hit by the second wave of the epidemic a few months earlier. Already in June 2020, newly confirmed cases had risen exponentially. As the COVID-19 pandemic is the first pandemic in which there has been instant sharing of genomic information on isolates around the world, the aim of this study was to analyze whole SARS-CoV-2 viral genomes from Serbia, to identify circulating variants/clade/lineages, and to explore site-specific mutational patterns in the unique early second wave of the European epidemic. This analysis of Serbian isolates represents the first publication from Balkan countries, which demonstrates the importance of specificities of local transmission especially when preventive measures differ among countries. One hundred forty-eight different genome variants among 41 Serbian isolates were detected in this study. One unique and seven extremely rare mutations were identified, with locally specific continuous dominance of the 20D clade. At the same time, amino acid substitutions of newly identified variants of concern were found in our isolates from October 2020. Future research should be focused on functional characterization of novel mutations in order to understand the exact role of these variations.

scholarly journals Gut microbiota, probiotics, prebiotics and bone health: a review

2018 ◽  
Vol 3 ◽  
pp. 101-110
Author(s):  
Nan Shang ◽  
Jianping Wu
Keyword(s):  
Gut Microbiota ◽  
Bone Metabolism ◽  
Bone Health ◽  
Health Management ◽  
Endocrine System ◽  
Pathogen Resistance ◽  
Bone Diseases ◽  
Future Research ◽  
Host Immune System ◽  
Metabolic Bone Diseases

Gut microbiota is widely accepted to play a crucial role to host health via the regulation of many physiological functions, including metabolism, nutrition, pathogen resistance, and immune function. Over the last decades, accumulating evidence has also pinpointed a role for gut microbiota on bone metabolism and the development of metabolic bone diseases, such as osteoporosis. Emerging evidence suggests the potential of gut microbiota as a promising target for bone health management. In this contribution, we have examined the available literature to understand the role of gut microbiota on bone metabolism as well as the underlying mechanisms. Furthermore, the application and effectiveness of using probiotics/prebiotics as means to modify gut microbiota and bone health are discussed. In this relation, animal studies and human trails suggest that alternation of gut microbiota composition can exert the activity of bone metabolism and therefore lead to the change of bone quality. It is believed that gut microbiota regulates bone metabolism via host immune system, endocrine system and mineral absorption. Supplementation with probiotics and prebiotics to both animals and humans has demonstrated promising, but sometimes conflicting results, on bone health. Thus, future research is expected to reveal the influence of the variations in age, gender, dose, delivery method, and treatment duration, among others on the probiotics/prebiotics-targeted bone diseases treatment.

scholarly journals Genome-Wide Identification, Evolution, and Transcriptional Profiling ofPP2CGene Family inBrassica rapa

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Nadeem Khan ◽  
Han Ke ◽  
Chun-mei Hu ◽  
Emal Naseri ◽  
Muhammad Salman Haider ◽  
...  
Keyword(s):  
Sequence Data ◽  
Transcriptional Profiling ◽  
Expression Patterns ◽  
Functional Characterization ◽  
Vital Role ◽  
Future Research ◽  
Evolutionary Analysis ◽  
Paralogous Gene ◽  
Gene Pairs ◽  
Genome Wide

The type 2C protein which belongs to the major group of protein phosphatases (PP2C) plays a vital role in abscisic acid (ABA) signaling and signal transductions processes. In the present study, 131PP2Cgenes were identified in total inBrassica rapaand categorized into thirteen subgroups based on their phylogenetic relationships. TheseB. rapaPP2C are structurally conserved based on amino acid sequence alignment, phylogenetic analysis, and conserved domains. Moreover, we utilized previously reported RNA-sequence data on various tissues (root, stem, leaf, flower, and silique), which suggests overlapping expression pattern in 29 paralogous gene pairs. The qRT-PCR validation of 15 paralogous gene pairs depicts distinct expression patterns in response to various abiotic stresses, such as heat, cold, ABA, and drought. Interestingly, stress-responsiveBraPP2Ccandidate genes were also identified, suggesting their significance in stress-tolerance mechanism inB. rapa. The evolutionary analysis for 15 paralogous gene pairs suggested that only three pairs have the positive selection and remaining were purifying in nature. The presented results of this study hasten our understanding of the molecular evolution of thePP2Cgene family inB. rapa. Thus, it will be ultimately helping in future research for facilitating the functional characterization ofBraPP2Cgenes in developing the abiotic stress tolerant plants.

Functional Characterization of Compliant Building Blocks Utilizing Eigentwists and Eigenwrenches

2008 ◽  
Author(s):  
Charles J. Kim
Keyword(s):  
Building Block ◽  
Compliant Mechanisms ◽  
Compliant Mechanism ◽  
Deformable Body ◽  
Functional Characterization ◽  
Building Blocks ◽  
Future Research ◽  
Special Cases ◽  
Block Approach

Compliant mechanisms are devices which utilize the flexibility of their constituent members to transmit motion and forces. Unlike their rigid body counterparts, compliant mechanisms typically contain no traditional joints. The focus of this research is the development of a building block approach for the synthesis of compliant mechanisms. Building block methods better facilitate the augmentation of designer intuition while offering a systematic approach to open-ended problems. In this paper, we investigate the use of the eigentwists and eigenwrenches of a deformable body to characterize basic kinematic function. The eigentwists and eigenwrenches are shown to demonstrate parametric behavior when applied to the compliant dyad building block, and in special cases may be compared to compliance ellipsoids. The paper concludes by articulating future research in a building block approach to compliant mechanism synthesis.

Sign in / Sign up

Export Citation Format

Share Document