Processing of Mass Spectrometry Data in Clinical Applications

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Presence of a Mitovirus Is Associated with Alteration of the Mitochondrial Proteome, as Revealed by Protein–Protein Interaction (PPI) and Co-Expression Network Models in Chenopodium quinoa Plants

SIMPLE SUMMARY: Plants often harbor persistent plant virus infection transmitted only vertically through seeds, resulting in no obvious symptoms (cryptic infections). Several studies have shown that such cryptic infections provide resilience against abiotic (and biotic) stress. We have recently discovered a new group of cryptic plant viruses infecting mitochondria (plant mitovirus). Mitochondria are cellular organelles displaying a pivotal role in protecting cells from the stress of nature . Here, we look at the proteomic alterations caused by the mitovirus cryptic infection of Chenopodium quinoa by Systems Biology approaches allowing one to evaluate data at holistic level. Quinoa is a domesticated plant species with many exciting features of abiotic stress resistance, and it is distinguished by its exceptional nutritional characteristics, such as the content and quality of proteins, minerals, lipids, and tocopherols. These features determined the growing interest for the quinoa crop by the scientific community and international organizations since they provide opportunities to produce high-value grains in arid, high-salt and high-UV agroecological environments. We discovered that quinoa lines hosting mitovirus activate some metabolic processes that might help them face drought. These findings present a new perspective for breeding crop plants through the augmented genome provided by accessory cryptic viruses to be investigated in the future. ABSTRACT: Plant mitoviruses belong to Mitoviridae family and consist of positive single-stranded RNA genomes replicating exclusively in host mitochondria. We previously reported the biological characterization of a replicating plant mitovirus, designated Chenopodium quinoa mitovirus 1 (CqMV1), in some Chenopodium quinoa accessions. In this study, we analyzed the mitochondrial proteome from leaves of quinoa, infected and not infected by CqMV1. Furthermore, by protein–protein interaction and co-expression network models, we provided a system perspective of how CqMV1 affects mitochondrial functionality. We found that CqMV1 is associated with changes in mitochondrial protein expression in a mild but well-defined way. In quinoa-infected plants, we observed up-regulation of functional modules involved in amino acid catabolism, mitochondrial respiratory chain, proteolysis, folding/stress response and redox homeostasis. In this context, some proteins, including BCE2 (lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex), DELTA-OAT (ornithine aminotransferase) and GR-RBP2 (glycine-rich RNA-binding protein 2) were interesting because all up-regulated and network hubs in infected plants; together with other hubs, including CAT (catalase) and APX3 (L-ascorbate peroxidase 3), they play a role in stress response and redox homeostasis. These proteins could be related to the higher tolerance degree to drought we observed in CqMV1-infected plants. Although a specific causative link could not be established by our experimental approach at this stage, the results suggest a new mechanistic hypothesis that demands further in-depth functional studies

Excitonic-insulator instability and Peierls distortion in one-dimensional semimetals

The charge density wave instability in one-dimensional semimetals is usually explained through a Peierls-like mechanism, where the coupling of electrons and phonons induces a periodic lattice distortion along certain modes of vibration, leading to a gap opening in the electronic band structure and to a lowering of the symmetry of the lattice. In this work, we study two prototypical Peierls systems: the one-dimensional carbon chain and the monatomic hydrogen chain with accurate ab initio calculations based on quantum Monte Carlo and hybrid density functional theory. We demonstrate that in one-dimensional semimetals at T=0, a purely electronic instability can exist independently of a lattice distortion. It is induced by spontaneous formation of low energy electron-hole pairs resulting in the electronic band gap opening, i.e., the destabilization of the semimetallic phase is due to an excitonic mechanism

Maximally-localized Wannier functions for disordered systems: application to amorphous silicon

We use the maximally-localized Wannier function method to study bonding properties in amorphous silicon. This study represents, to our knowledge, the first application of the Wannier-function analysis to a disordered system. Our results show that, in the presence of disorder, this method is extremely helpful in providing an unambiguous picture of the bond distribution. In particular, defect configurations can be studied and characterized with a novel degree of accuracy that was not available before.Comment: 4 pages, with 3 PostScript figures embedded. Uses RevTex and epsf macros. Also available at http://www.physics.rutgers.edu/~dhv/preprints/index.html#nm_as

Theranostics in Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually: 10B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount of 10B in the tumor but also on the organs at risk. It is not yet possible to determine the 10B concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure the 10B concentration in blood and to estimate the boron concentration in tissues based on the assumption that there is a fixed uptake of 10B from the blood into tissues. On this imprecise assumption, BNCT can hardly be developed further. A therapeutic approach, combining the boron carrier for therapeutic purposes with an imaging tool, might allow us to determine the 10B concentration in a specific tissue using a non-invasive method. This review provides an overview of the current clinical protocols and preclinical experiments and results on how innovative drug development for boron delivery systems can also incorporate concurrent imaging. The last section focuses on the importance of proteomics for further optimization of BNCT, a highly precise and personalized therapeutic approach

Theranostics in Boron neutron capture therapy

Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually:B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount ofB in the tumor but also on the organs at risk. It is not yet possible to determine theB concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure theB concentration in blood and to estimate the boron concentration in tissues based on the assumption that there is a fixed uptake ofB from the blood into tissues. On this imprecise assumption, BNCT can hardly be developed further. A therapeutic approach, combining the boron carrier for therapeutic purposes with an imaging tool, might allow us to determine theB concentration in a specific tissue using a non-invasive method. This review provides an overview of the current clinical protocols and preclinical experiments and results on how innovative drug development for boron delivery systems can also incorporate concurrent imaging. The last section focuses on the importance of proteomics for further optimization of BNCT, a highly precise and personalized therapeutic approach.E.H.-H. and M.K. gratefully acknowledge support from the DFG (HE 1376/38-1); L.S. received funding from GEFLUC Grenoble Dauphiné Savoie

Interaction of SARS-CoV-2 Nucleocapsid Protein and Human RNA Helicases DDX1 and DDX3X Modulates Their Activities on Double-Stranded RNA

The nucleocapsid protein Np of SARS-CoV-2 is involved in the replication, transcription, and packaging of the viral genome, but it also plays a role in the modulation of the host cell innate immunity and inflammation response. Ectopic expression of Np alone was able to induce significant changes in the proteome of human cells. The cellular RNA helicase DDX1 was among the proteins whose levels were increased by Np expression. DDX1 and its related helicase DDX3X were found to physically interact with Np and to increase 2- to 4-fold its affinity for double-stranded RNA in a helicase-independent manner. Conversely, Np inhibited the RNA helicase activity of both proteins. These functional interactions among Np and DDX1 and DDX3X highlight novel possible roles played by these host RNA helicases in the viral life cycle.ISSN:1422-006

Proteomic analysis of Mesembryanthemum crystallinum leaf microsomal fractions finds an imbalance in V-ATPase stoichiometry during the salt-induced transition from C3 to CAM.

The halophyte Mesembryanthemum crystallinum adapts to salt stress by salt uptake and switching from C3 photosynthesis to CAM (crassulacean acid metabolism). An important role in this process is played by transport proteins in the tonoplast of the central vacuole. In the present study we examine dynamic changes in the protein composition during salt-stress adaptation in microsomes from M. crystallinum leaves. Plants challenged with 400 mM NaCl accumulate salt by day 4 of treatment and malic acid only at day 12; a switching to CAM hence follows any initial steps of salt adaptation with a delay. Using a label-free and semiquantitative approach, we identified the most dramatic changes between the proteome of control plants and plants harvested after 12 days of the treatment; the abundance of 14 proteins was significantly affected. The proteomic data revealed that the majority of the subunits of V-ATPase (vacuolar H(+)-ATPase) holoenzyme. The salt treatment somewhat decreased the abundance of all subunits in the short term (4 days). Long-term adaptation, including the switching to CAM, goes together with a strong increase in the representation of all detectable subunits. Because this increase is subunit-specific, with the highest rise occurring for subunits E and c, the data suggest that long-term adaptation to salt stress correlates with a change in V-ATPase subunit stoichiometry and highlight the structural plasticity of this holoenzyme

Theranostics in Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually: 10B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount of 10B in the tumor but also on the organs at risk. It is not yet possible to determine the 10B concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure the 10B concentration in blood and to estimate the boron concentration in tissues based on the assumption that there is a fixed uptake of 10B from the blood into tissues. On this imprecise assumption, BNCT can hardly be developed further. A therapeutic approach, combining the boron carrier for therapeutic purposes with an imaging tool, might allow us to determine the 10B concentration in a specific tissue using a non-invasive method. This review provides an overview of the current clinical protocols and preclinical experiments and results on how innovative drug development for boron delivery systems can also incorporate concurrent imaging. The last section focuses on the importance of proteomics for further optimization of BNCT, a highly precise and personalized therapeutic approach

Theranostics in Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually: 10B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount of 10B in the tumor but also on the organs at risk. It is not yet possible to determine the 10B concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure the 10B concentration in blood and to estimate the boron concentration in tissues based on the assumption that there is a fixed uptake of 10B from the blood into tissues. On this imprecise assumption, BNCT can hardly be developed further. A therapeutic approach, combining the boron carrier for therapeutic purposes with an imaging tool, might allow us to determine the 10B concentration in a specific tissue using a non-invasive method. This review provides an overview of the current clinical protocols and preclinical experiments and results on how innovative drug development for boron delivery systems can also incorporate concurrent imaging. The last section focuses on the importance of proteomics for further optimization of BNCT, a highly precise and personalized therapeutic approach