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Papers by Dominique Derminio
Schizophrenia is a mental disorder that affects approximately 1% of the world’s population. The N... more Schizophrenia is a mental disorder that affects approximately 1% of the world’s population. The N-methyl-d-aspartate receptor (NMDAR) seems likely to play a prominent role in schizophrenia; as when NMDAR antagonists are introduced, psychosis occurs in individuals with no mental disorders. This thesis explores how NMDAR may be endogenously changed in the brains of people with schizophrenia. By using tissue fractionation, discussed in chapter 3, to examine the post-synaptic density (PSD) specifically one can specifically examine the NMDAR protein at the synapse of the neuron. Also, one can examine the NMDAR mRNA level in the brains of people with schizophrenia compared to controls. My Masters’ thesis research covers four broad areas, namely subcellular tissue fractionation of human cerebral cortex, the determination of the NMDAR subunit NR1 protein levels specifically in the PSD, analysis of NR1 mRNA transcript across cortical lamina, and the quantification of NMDAR NR1 mRNA at the ce...
Frontiers in Microbiology, 2020
Microcystins produced during harmful cyanobacterial blooms are a public health concern. Although ... more Microcystins produced during harmful cyanobacterial blooms are a public health concern. Although patterns are emerging, the environmental cues that stimulate production of microcystin remain confusing, hindering our ability to predict fluctuations in bloom toxicity. In earlier work, growth at cool temperatures relative to optimum (18°C vs. 26°C) was confirmed to increase microcystin quota in batch cultures of Microcystis aeruginosa NIES-843. Here, we tested this response in M. aeruginosa PCC 7806 using continuous cultures to examine temporal dynamics and using RNA-sequencing to investigate the physiological nature of the response. A temperature reduction from 26 to 19°C increased microcystin quota ∼2-fold, from an average of ∼464 ag μm–3 cell volume to ∼891 ag μm–3 over a 7–9 d period. Reverting the temperature to 26°C returned the cellular microcystin quota to ∼489 ag μm–3. Long periods (31–42 d) at 19°C did not increase or decrease microcystin quota beyond that observed at 7–9 d. ...
npj Schizophrenia, 2015
Background: There is converging evidence of involvement of N-methyl-d-aspartate (NMDA) receptor h... more Background: There is converging evidence of involvement of N-methyl-d-aspartate (NMDA) receptor hypofunction in the pathophysiology of schizophrenia. Our group recently identified a decrease in total NR1 mRNA and protein expression in the dorsolateral prefrontal cortex in a case-control study of individuals with schizophrenia (n=37/group). The NR1 subunit is critical to NMDA receptor function at the postsynaptic density, a cellular structure rich in the scaffolding protein, PSD-95. The extent to which the NMDA receptor NR1 subunit is altered at the site of action, in the postsynaptic density, is not clear. Aims: To extend our previous results by measuring levels of NR1 and PSD-95 protein in postsynaptic density-enriched fractions of prefrontal cortex from the same individuals in the case-control study noted above. Methods: Postsynaptic density-enriched fractions were isolated from fresh-frozen prefrontal cortex (BA10) and subjected to western blot analysis for NR1 and PSD-95. Result...
D. S. Derminio. Interactions between light and production of microcystins in the toxic cyanobacte... more D. S. Derminio. Interactions between light and production of microcystins in the toxic cyanobacterium Microcystis. 242 pages, 13 tables, 57 figures, 2020. Harvard citation. Cyanobacterial harmful algal blooms (cHABs) are characterized by the formation of toxins that can impact animal health, cause water quality issues, and recreational hazards. Microcystis, a common genus of cyanobacteria, produces the potent protein phosphatase inhibitor microcystins. Microcystins are nitrogen-rich and have an associated metabolic cost for production. Some outstanding questions in the study of cHABs is why are microcystins produced, what are the benefits of toxin formation, and why only some Microcystis strains produce microcystins? We examined a potential biochemical role for microcystins in the cyanobacterial photosystem regulation in response to various light conditions. Single-celled culture strains of toxic and nontoxic Microcystis aeruginosa were grown under different light irradiances. Highlight conditions caused light stress based on decreased photosynthetic efficiency. Cells responded over 2-3 days by decreasing their chlorophyll and phycobilisome content per cell in unison. Looking at a natural system over a diurnal cycle of changing light intensities, Microcystis responded to highlight environments via vertical migration deeper in the water column to avoid light stress. In one culture and in situ, there were no changes in microcystins concentration per cell, but one strain showed decreased microcystins under low-light. Therefore, microcystins protein phosphatase activity may not be involved with phosphorylation/dephosphorylation under highlight. Highlight environments are also associated reactive oxygen species (ROS) production. We investigated if microcystins were linked to ROS sensitivity by examining how three chlorophytes and seven cyanobacteria responded to the ROS compound hydrogen peroxide (H 2 O 2). There was no evidence that toxic cyanobacteria were more sensitive to ROS than non-toxic cyanobacteria or chlorophytes. Addition of H 2 O 2 did not change the microcystins concentration per cell. While these experiments did not elucidate the biochemical function of microcystins in Microcystis, they provided valuable information for water quality managers. cHAB monitoring programs must carefully consider vertical migration away from the surface during highlight conditions. The use of H 2 O 2 as a control mechanism may not selectively remove toxic cyanobacteria. Despite visual similarities, Microcystis is composed of diverse species with a wide-range of responses to light and ROS. Care must be taken when applying conclusions using a limited number of strains to broader populations.
Schizophrenia is a mental disorder that affects approximately 1% of the world’s population. The N... more Schizophrenia is a mental disorder that affects approximately 1% of the world’s population. The N-methyl-d-aspartate receptor (NMDAR) seems likely to play a prominent role in schizophrenia; as when NMDAR antagonists are introduced, psychosis occurs in individuals with no mental disorders. This thesis explores how NMDAR may be endogenously changed in the brains of people with schizophrenia. By using tissue fractionation, discussed in chapter 3, to examine the post-synaptic density (PSD) specifically one can specifically examine the NMDAR protein at the synapse of the neuron. Also, one can examine the NMDAR mRNA level in the brains of people with schizophrenia compared to controls. My Masters’ thesis research covers four broad areas, namely subcellular tissue fractionation of human cerebral cortex, the determination of the NMDAR subunit NR1 protein levels specifically in the PSD, analysis of NR1 mRNA transcript across cortical lamina, and the quantification of NMDAR NR1 mRNA at the ce...
Frontiers in Microbiology, 2020
Microcystins produced during harmful cyanobacterial blooms are a public health concern. Although ... more Microcystins produced during harmful cyanobacterial blooms are a public health concern. Although patterns are emerging, the environmental cues that stimulate production of microcystin remain confusing, hindering our ability to predict fluctuations in bloom toxicity. In earlier work, growth at cool temperatures relative to optimum (18°C vs. 26°C) was confirmed to increase microcystin quota in batch cultures of Microcystis aeruginosa NIES-843. Here, we tested this response in M. aeruginosa PCC 7806 using continuous cultures to examine temporal dynamics and using RNA-sequencing to investigate the physiological nature of the response. A temperature reduction from 26 to 19°C increased microcystin quota ∼2-fold, from an average of ∼464 ag μm–3 cell volume to ∼891 ag μm–3 over a 7–9 d period. Reverting the temperature to 26°C returned the cellular microcystin quota to ∼489 ag μm–3. Long periods (31–42 d) at 19°C did not increase or decrease microcystin quota beyond that observed at 7–9 d. ...
npj Schizophrenia, 2015
Background: There is converging evidence of involvement of N-methyl-d-aspartate (NMDA) receptor h... more Background: There is converging evidence of involvement of N-methyl-d-aspartate (NMDA) receptor hypofunction in the pathophysiology of schizophrenia. Our group recently identified a decrease in total NR1 mRNA and protein expression in the dorsolateral prefrontal cortex in a case-control study of individuals with schizophrenia (n=37/group). The NR1 subunit is critical to NMDA receptor function at the postsynaptic density, a cellular structure rich in the scaffolding protein, PSD-95. The extent to which the NMDA receptor NR1 subunit is altered at the site of action, in the postsynaptic density, is not clear. Aims: To extend our previous results by measuring levels of NR1 and PSD-95 protein in postsynaptic density-enriched fractions of prefrontal cortex from the same individuals in the case-control study noted above. Methods: Postsynaptic density-enriched fractions were isolated from fresh-frozen prefrontal cortex (BA10) and subjected to western blot analysis for NR1 and PSD-95. Result...
D. S. Derminio. Interactions between light and production of microcystins in the toxic cyanobacte... more D. S. Derminio. Interactions between light and production of microcystins in the toxic cyanobacterium Microcystis. 242 pages, 13 tables, 57 figures, 2020. Harvard citation. Cyanobacterial harmful algal blooms (cHABs) are characterized by the formation of toxins that can impact animal health, cause water quality issues, and recreational hazards. Microcystis, a common genus of cyanobacteria, produces the potent protein phosphatase inhibitor microcystins. Microcystins are nitrogen-rich and have an associated metabolic cost for production. Some outstanding questions in the study of cHABs is why are microcystins produced, what are the benefits of toxin formation, and why only some Microcystis strains produce microcystins? We examined a potential biochemical role for microcystins in the cyanobacterial photosystem regulation in response to various light conditions. Single-celled culture strains of toxic and nontoxic Microcystis aeruginosa were grown under different light irradiances. Highlight conditions caused light stress based on decreased photosynthetic efficiency. Cells responded over 2-3 days by decreasing their chlorophyll and phycobilisome content per cell in unison. Looking at a natural system over a diurnal cycle of changing light intensities, Microcystis responded to highlight environments via vertical migration deeper in the water column to avoid light stress. In one culture and in situ, there were no changes in microcystins concentration per cell, but one strain showed decreased microcystins under low-light. Therefore, microcystins protein phosphatase activity may not be involved with phosphorylation/dephosphorylation under highlight. Highlight environments are also associated reactive oxygen species (ROS) production. We investigated if microcystins were linked to ROS sensitivity by examining how three chlorophytes and seven cyanobacteria responded to the ROS compound hydrogen peroxide (H 2 O 2). There was no evidence that toxic cyanobacteria were more sensitive to ROS than non-toxic cyanobacteria or chlorophytes. Addition of H 2 O 2 did not change the microcystins concentration per cell. While these experiments did not elucidate the biochemical function of microcystins in Microcystis, they provided valuable information for water quality managers. cHAB monitoring programs must carefully consider vertical migration away from the surface during highlight conditions. The use of H 2 O 2 as a control mechanism may not selectively remove toxic cyanobacteria. Despite visual similarities, Microcystis is composed of diverse species with a wide-range of responses to light and ROS. Care must be taken when applying conclusions using a limited number of strains to broader populations.