| 1. |
- Srivastava, Vaibhav, et al.
(författare)
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OnPLS integration of transcriptomic, proteomic and metabolomic data shows multi-level oxidative stress responses in the cambium of transgenic hipI- superoxide dismutase Populus plants
- 2013
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Ingår i: BMC Genomics. - : BioMed Central. - 1471-2164. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Reactive oxygen species (ROS) are involved in the regulation of diverse physiological processes in plants, including various biotic and abiotic stress responses. Thus, oxidative stress tolerance mechanisms in plants are complex, and diverse responses at multiple levels need to be characterized in order to understand them. Here we present system responses to oxidative stress in Populus by integrating data from analyses of the cambial region of wild-type controls and plants expressing high-isoelectric-point superoxide dismutase (hipI-SOD) transcripts in antisense orientation showing a higher production of superoxide. The cambium, a thin cell layer, generates cells that differentiate to form either phloem or xylem and is hypothesized to be a major reason for phenotypic perturbations in the transgenic plants. Data from multiple platforms including transcriptomics (microarray analysis), proteomics (UPLC/QTOF-MS), and metabolomics (GC-TOF/MS, UPLC/MS, and UHPLC-LTQ/MS) were integrated using the most recent development of orthogonal projections to latent structures called OnPLS. OnPLS is a symmetrical multi-block method that does not depend on the order of analysis when more than two blocks are analysed. Significantly affected genes, proteins and metabolites were then visualized in painted pathway diagrams.RESULTS: The main categories that appear to be significantly influenced in the transgenic plants were pathways related to redox regulation, carbon metabolism and protein degradation, e.g. the glycolysis and pentose phosphate pathways (PPP). The results provide system-level information on ROS metabolism and responses to oxidative stress, and indicate that some initial responses to oxidative stress may share common pathways.CONCLUSION: The proposed data evaluation strategy shows an efficient way of compiling complex, multi-platform datasets to obtain significant biological information.
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| 2. |
- Vyas, Sachin, et al.
(författare)
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Structural and Molecular Characterization of Squalene Synthase Belonging to the Marine Thraustochytrid Species Aurantiochytrium limacinum Using Bioinformatics Approach
- 2022
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Ingår i: Marine Drugs. - : MDPI. - 1660-3397 .- 1660-3397. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- The marine microorganisms thraustochytrids have been explored for their potential in the production of various bioactive compounds, such as DHA, carotenoids, and squalene. Squalene is a secondary metabolite of the triterpenoid class and is known for its importance in various industrial applications. The bioinformatic analysis for squalene synthase (SQS) gene (the first key enzyme in the tri-terpenoid synthesis pathway), that is prevailing among thraustochytrids, is poorly investigated. In-silico studies combining sequence alignments and bioinformatic tools helped in the preliminary characterization of squalene synthases found in Aurantiochytrium limacinum. The sequence contained highly conserved regions for SQS found among different species indicated the enzyme had all the regions for its functionality. The signal peptide sequence and transmembrane regions were absent, indicating an important aspect of the subcellular localization. Secondary and 3-D models generated using appropriate templates demonstrated the similarities with SQS of the other species. The 3-D model also provided important insights into possible active, binding, phosphorylation, and glycosylation sites.
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| 3. |
- Mulliri, Simone, et al.
(författare)
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Spectroscopic and In Silico Studies on the Interaction of Substituted Pyrazolo[1,2-a]benzo[1,2,3,4]tetrazine-3-one Derivatives with c-Myc G4-DNA
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:11
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Tidskriftsartikel (refereegranskat)abstract
- Herein we describe a combined experimental and in silico study of the interaction of a series of pyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-one derivatives (PBTs) with parallel G-quadruplex (GQ) DNA aimed at correlating their previously reported anticancer activities and the stabilizing effects observed by us on c-myc oncogene promoter GQ structure. Circular dichroism (CD) melting experiments were performed to characterize the effect of the studied PBTs on the GQ thermal stability. CD measurements indicate that two out of the eight compounds under investigation induced a slight stabilizing effect (2–4 °C) on GQ depending on the nature and position of the substituents. Molecular docking results allowed us to verify the modes of interaction of the ligands with the GQ and estimate the binding affinities. The highest binding affinity was observed for ligands with the experimental melting temperatures (Tms). However, both stabilizing and destabilizing ligands showed similar scores, whilst Molecular Dynamics (MD) simulations, performed across a wide range of temperatures on the GQ in water solution, either unliganded or complexed with two model PBT ligands with the opposite effect on the Tms, consistently confirmed their stabilizing or destabilizing ability ascertained by CD. Clues about a relation between the reported anticancer activity of some PBTs and their ability to stabilize the GQ structure of c-myc emerged from our study. Furthermore, Molecular Dynamics simulations at high temperatures are herein proposed for the first time as a means to verify the stabilizing or destabilizing effect of ligands on the GQ, also disclosing predictive potential in GQ-targeting drug discovery.
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| 4. |
- Neamtu, Andrei, et al.
(författare)
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Towards an optimal monoclonal antibody with higher binding affinity to the receptor-binding domain of SARS-CoV-2 spike proteins from different variants
- 2023
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Ingår i: Colloids and Surfaces B. - : Elsevier. - 0927-7765 .- 1873-4367. ; 221
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Tidskriftsartikel (refereegranskat)abstract
- A highly efficient and robust multiple scales in silico protocol, consisting of atomistic Molecular Dynamics (MD), coarse-grain (CG) MD, and constant-pH CG Monte Carlo (MC), has been developed and used to study the binding affinities of selected antigen-binding fragments of the monoclonal antibody (mAbs) CR3022 and several of its here optimized versions against 11 SARS-CoV-2 variants including the wild type. Totally 235,000 mAbs structures were initially generated using the RosettaAntibodyDesign software, resulting in top 10 scored CR3022-like-RBD complexes with critical mutations and compared to the native one, all having the potential to block virus-host cell interaction. Of these 10 finalists, two candidates were further identified in the CG simulations to be the best against all SARS-CoV-2 variants. Surprisingly, all 10 candidates and the native CR3022 exhibited a higher affinity for the Omicron variant despite its highest number of mutations. The multiscale protocol gives us a powerful rational tool to design efficient mAbs. The electrostatic interactions play a crucial role and appear to be controlling the affinity and complex building. Studied mAbs carrying a more negative total net charge show a higher affinity. Structural determinants could be identified in atomistic simulations and their roles are discussed in detail to further hint at a strategy for designing the best RBD binder. Although the SARS-CoV-2 was specifically targeted in this work, our approach is generally suitable for many diseases and viral and bacterial pathogens, leukemia, cancer, multiple sclerosis, rheumatoid, arthritis, lupus, and more.
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| 5. |
- Gahan, Chandra Sekhar, et al.
(författare)
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Effect of chloride on ferrous iron oxidation by a leptospirillum ferriphilum-dominated chemostat culture
- 2010
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Ingår i: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 106:3, s. 422-431
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Tidskriftsartikel (refereegranskat)abstract
- Biomining is the use of microorganisms to catalyze metal extraction from sulfide ores. However, the available water in some biomining environments has high chloride concentrations and therefore, chloride toxicity to ferrous oxidizing microorganisms has been investigated. Batch biooxidation of Fe2+ by a Leptospirillum ferriphilum dominated culture was completely inhibited by 12gL(-1) chloride. In addition, the effects of chloride on oxidation kinetics in a Fe2+ limited chemostat were studied. Results from the chemostat modeling suggest that the chloride toxicity was attributed to affects on the Fe2+ oxidation system, pH homeostasis, and lowering of the proton motive force. Modeling showed a decrease in the maximum specific growth rate (mu(max)) and an increase in the substrate constant (K-s) with increasing chloride concentrations, indicating an effect on the Fe2+ oxidation system. The model proposes a lowered maintenance activity when the media was fed with 2-3 g L-1 chloride with a concomitant drastic decrease in the true yield (Y-true). This model helps to understand the influence of chloride on Fe2+ biooxidation kinetics. Biotechnol. Bioeng. 2010;106: 422-431. (C) 2010 Wiley Periodicals, Inc.
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| 6. |
- Giron, Carolina Corrêa, et al.
(författare)
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Differences between Omicron SARS-CoV-2 RBD and other variants in their ability to interact with cell receptors and monoclonal antibodies
- 2023
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Ingår i: Journal of Biomolecular Structure and Dynamics. - : Taylor & Francis. - 0739-1102 .- 1538-0254. ; 41:12, s. 5707-5727
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Tidskriftsartikel (refereegranskat)abstract
- SARS-CoV-2 remains a health threat with the continuous emergence of new variants. This work aims to expand the knowledge about the SARS-CoV-2 receptor-binding domain (RBD) interactions with cell receptors and monoclonal antibodies (mAbs). By using constant-pH Monte Carlo simulations, the free energy of interactions between the RBD from different variants and several partners (Angiotensin-Converting Enzyme-2 (ACE2) polymorphisms and various mAbs) were predicted. Computed RBD-ACE2-binding affinities were higher for two ACE2 polymorphisms (rs142984500 and rs4646116) typically found in Europeans which indicates a genetic susceptibility. This is amplified for Omicron (BA.1) and its sublineages BA.2 and BA.3. The antibody landscape was computationally investigated with the largest set of mAbs so far in the literature. From the 32 studied binders, groups of mAbs were identified from weak to strong binding affinities (e.g. S2K146). These mAbs with strong binding capacity and especially their combination are amenable to experimentation and clinical trials because of their high predicted binding affinities and possible neutralization potential for current known virus mutations and a universal coronavirus.
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| 7. |
- Gowda, Vasantha, et al.
(författare)
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Structural characterisation of amyloid-like fibrils formed by an amyloidogenic peptide segment of β-lactoglobulin
- 2021
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 11:45, s. 27868-27879
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Tidskriftsartikel (refereegranskat)abstract
- Protein nanofibrils (PNFs) represent a promising class of biobased nanomaterials for biomedical and materials science applications. In the design of such materials, a fundamental understanding of the structure–function relationship at both molecular and nanoscale levels is essential. Here we report investigations of the nanoscale morphology and molecular arrangement of amyloid-like PNFs of a synthetic peptide fragment consisting of residues 11–20 of the protein β-lactoglobulin (β-LG11–20), an important model system for PNF materials. Nanoscale fibril morphology was analysed by atomic force microscopy (AFM) that indicates the presence of polymorphic self-assembly of protofilaments. However, observation of a single set of 13C and 15N resonances in the solid-state NMR spectra for the β-LG11–20 fibrils suggests that the observed polymorphism originates from the assembly of protofilaments at the nanoscale but not from the molecular structure. The secondary structure and inter-residue proximities in the β-LG11–20 fibrils were probed using NMR experiments of the peptide with 13C- and 15N-labelled amino acid residues at selected positions. We can conclude that the peptides form parallel β-sheets, but the NMR data was inconclusive regarding inter-sheet packing. Molecular dynamics simulations confirm the stability of parallel β-sheets and suggest two preferred modes of packing. Comparison of molecular dynamics models with NMR data and calculated chemical shifts indicates that both packing models are possible.
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| 8. |
- Krupodorova, TA, et al.
(författare)
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Review of the basic cultivation conditions influence on the growth of basidiomycetes
- 2021
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Ingår i: Current Research in Environmental and Applied Mycology (Journal of Fungal Biology). - : Institute of Plant and Environment Protection (IPEP). - 2229-2225. ; 11:1, s. 494-531
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Forskningsöversikt (refereegranskat)abstract
- Recently, the significant economic and therapeutic potential of different fungi causes the intense cultivation of the prospective species. This review presents the analysis of the basic physicochemical conditions for fungi cultivation that have an influence on basidiomycetes’ mycelia or biomass growth options (maximal mycelial dry weight, maximal mycelial growth, maximal mycelial growth rate, mycelial density, colony diameter, etc.). Not only different species, but different strains of the same fungus require different cultivation conditions, the variability of nutrition media, temperature, pH, carbon and nitrogen sources. Several parameters optimal cultivation can be explained by the geographical and climatic factors. Analysis of literature data and the resulting conclusions will help a deeper understanding of the biological characteristics of fungi, their nutritional needs, optimal temperature and pH, and optimization of the production of fungal biomass. Comparison of the collected information on various fungal strains growth aimed to facilitate the further development and optimization in existing cultivation protocols. According to this, the maximum growth for biotechnological and industrial application is expected to be obtained. Also, the prolongation in safekeeping of viable fungal forms and the preservation of the fungi biodiversity for their re-introduction in nature is expected as one of the benefits after protocol optimization.
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| 9. |
- Latham, Kenneth G., et al.
(författare)
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Impact of Temperature and Residence Time on the Hydrothermal Carbonization of Organosolv Lignin
- 2022
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Ingår i: Journal of Analytical and Applied Pyrolysis. - : Elsevier. - 0165-2370 .- 1873-250X. ; 166
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Tidskriftsartikel (refereegranskat)abstract
- Herein, we have investigated how pure lignin extracted from birch and spruce via a hybrid organosolv/steam explosion method reacts under hydrothermal carbonization (HTC) to produce hydrochar, a product that has found applications in environmental remediation, energy storage and catalysis. We subjected thirteen lignin samples obtained from birch and spruce under different extraction conditions to HTC at 260 ℃ for four hours. The yield of hydrochar varied between the different extraction conditions and source, although no clear correlation between extraction conditions and yield could be observed. For instance, lignin from birch pretreated in 60%v/v ethanol for 15 minutes resulted in a hydrochar yield of 39 wt%. Increasing the time to 30 and 60 resulted in a hydrochar yield of 27 wt% and 23 wt%, respectively. This suggested that small changes in the organosolv reaction conditions might produce highly structurally different lignin, resulting in the difference in HTC yield. Thus, we chose a subset of four lignin samples to investigate in-depth, subjecting these samples to a range of hydrothermal reaction temperatures and residence times. Solid State NMR and FTIR analysis indicated that the most significant structural changes occurred below 230 ℃ resulting in the breaking of C-O- linkages. Increasing the temperature or time had minimal impact, with no further C-O- linkages broken and no changes to the ring structure of C-C groups. Size exclusion chromatography indicated that the degree of micro and macromolecules in the liquid product varied significantly with lignin source and HTC reaction conditions. Overall, this study demonstrated that lignin has a large reaction range where it produces a very chemically similar solid product, with the only major difference being the yield of material. This is important for industry, as it indicates that a similar solid product can be easily achieved independently of extraction conditions allowing the HTC reaction to be tuned towards extracting the maximum benefit from products contained in the liquid.
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| 10. |
- Mariam, Iqra, et al.
(författare)
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Ameliorating microalgal OMEGA production using omics platforms
- 2024
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Ingår i: Trends in Plant Science. - : Elsevier Ltd. - 1360-1385 .- 1878-4372.
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Forskningsöversikt (refereegranskat)abstract
- Over the past decade, the focus on omega (ω)-3 fatty acids from microalgae has intensified due to their diverse health benefits. Bioprocess optimization has notably increased ω-3 fatty acid yields, yet understanding of the genetic architecture and metabolic pathways of high-yielding strains remains limited. Leveraging genomics, transcriptomics, proteomics, and metabolomics tools can provide vital system-level insights into native ω-3 fatty acid-producing microalgae, further boosting production. In this review, we explore ‘omics’ studies uncovering alternative pathways for ω-3 fatty acid synthesis and genome-wide regulation in response to cultivation parameters. We also emphasize potential targets to fine-tune in order to enhance yield. Despite progress, an integrated omics platform is essential to overcome current bottlenecks in optimizing the process for ω-3 fatty acid production from microalgae, advancing this crucial field.
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