Leafy green vegetables contain essential nutrients and are frequently consumed for their perceive... more Leafy green vegetables contain essential nutrients and are frequently consumed for their perceived health benefits. The purpose of this study was to profile the nutritional and natural bioactive phytochemical compounds extracted from freeze-dried spinach and kale and compare them with our previously published freeze-dried purslane results. Novel research suggests that these leafy greens contain an abundance of fatty acids, amino acids, organic acids, vitamins, and minerals, which can reduce the risk of many chronic diseases. LC-MS/MS screening identified 69 and 103 compounds in spinach and kale, respectively, including flavonoids, glucosinolates, and phenolic and organic acids. Out of a total of 26 flavonoids identified in the current study, only three were found in spinach. All three leafy greens showed nutritional and health benefits and the unique phytochemical compounds found only in purslane provide a strong basis to incorporate its distinct dietary benefits.
Provided by the author(s) and NUI Galway in accordance with publisher policies. Please cite the p... more Provided by the author(s) and NUI Galway in accordance with publisher policies. Please cite the published version when available. Downloaded 2016-05-17T05:32:42Z Some rights reserved. For more information, please see the item record link above.
Coffee cherry is a rich source of chlorogenic acids (CGAs) and caffeine. In this study we examine... more Coffee cherry is a rich source of chlorogenic acids (CGAs) and caffeine. In this study we examined the potential antioxidant activity and enzyme inhibitory effects of whole coffee cherries (WCC) and their two extracts on α-amylase, α-glucosidase and acetylcholinesterase (AChE) activities, which are targets for the control of diabetes and Alzheimer’s diseases. Whole coffee cherry extract 40% (WCCE1) is rich in chlorogenic acid compounds, consisting of a minimum of 40% major isomers, namely 3-caffeoylquinic acids, 4-caffeoylquinic acids, 5-caffeoylquinic acids, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, 4-feruloylquinc acid, and 5-feruloylquinc acid. Whole coffee cherry extract 70% (WCCE2) is rich in caffeine, with a minimum of 70%. WCCE1 inhibited the activities of digestive enzymes α-amylase and α-glucosidase, and WCCE2 inhibited acetylcholinesterase activities with their IC50 values of 1.74, 2.42, and 0.09 mg/mL, respectively. Multiple antioxid...
Proceedings of the National Academy of Sciences, 2018
Significance Double-strand breaks (DSBs) in the DNA are the most dangerous type of damage and mus... more Significance Double-strand breaks (DSBs) in the DNA are the most dangerous type of damage and must be repaired to maintain genome integrity, avoiding disease-linked mutations and cancer initiation/progression. The NuA4 histone acetyltransferase complex is recruited to DNA DSBs to facilitate repair through modification of the chromatin surrounding the damage, but its recruitment mechanism is poorly understood. Here, we report that the DNA damage sensor complex Mre11-Rad50-Xrs2 physically recruits NuA4 to the break sites followed by bidirectional spreading linked to the DNA end resection required for error-free repair by homologous recombination. During that process, NuA4 can acetylate ssDNA-binding replication protein A (RPA), leading to its displacement.
Histone deacetylases (HDACs) catalyze the removal of acetylation marks from lysine residues on hi... more Histone deacetylases (HDACs) catalyze the removal of acetylation marks from lysine residues on histone and nonhistone substrates. Their activity is generally associated with essential cellular processes such as transcriptional repression and heterochromatin formation. Interestingly, abnormal activity of HDACs has been reported in various types of cancers, which makes them a promising therapeutic target for cancer treatment. In the current study, we aim to understand the mechanisms underlying the function of HDACs using an in-depth quantitative analysis of changes in histone acetylation levels in Schizosaccharomyces pombe (S. pombe) lacking major HDAC activities. We employed a targeted quantitative mass spectrometry approach to profile changes of acetylation and methylation at multiple lysine residues on the N-terminal tail of histones H3 and H4. Our analyses identified a number of histone acetylation sites that are significantly affected by S. pombe HDAC mutations. We discovered that mutation of the Class I HDAC known as Clr6 causes a major increase in the abundance of triacetylated H4 molecules at K5, K8, and K12. A clr6-1 hypomorphic mutation also increased the abundance of multiple acetyl-lysines in histone H3. In addition, our study uncovered a few crosstalks between histone acetylation and methylation upon deletion of HDACs Hos2 and Clr3. We anticipate that the results from this study will greatly improve our current understanding of the mechanisms involved in HDAC-mediated gene regulation and heterochromatin assembly.
In Saccharomyces cerevisiae, histone H3 lysine 56 acetylation (H3K56Ac) is present in newly synth... more In Saccharomyces cerevisiae, histone H3 lysine 56 acetylation (H3K56Ac) is present in newly synthesized histones deposited throughout the genome during DNA replication. The sirtuins Hst3 and Hst4 deacetylate H3K56 after S-phase, and virtually all histone H3 molecules are K56-acetylated throughout the cell cycle in hst3∆ hst4∆ mutants. Failure to deacetylate H3K56 causes thermosensitivity, spontaneous DNA damage, and sensitivity to replicative stress via molecular mechanisms that remain unclear. Here we demonstrate that, unlike wild-type cells, hst3∆ hst4∆ cells are unable to complete genome duplication and accumulate persistent foci containing the homologous recombination protein Rad52 after exposure to genotoxic drugs during S-phase. In response to replicative stress, cells lacking Hst3 and Hst4 also displayed intense foci containing the Rfa1 subunit of the single-stranded DNA binding protein complex RPA, as well as persistent activation of DNA damage-induced kinases. To investigat...
Leafy green vegetables contain essential nutrients and are frequently consumed for their perceive... more Leafy green vegetables contain essential nutrients and are frequently consumed for their perceived health benefits. The purpose of this study was to profile the nutritional and natural bioactive phytochemical compounds extracted from freeze-dried spinach and kale and compare them with our previously published freeze-dried purslane results. Novel research suggests that these leafy greens contain an abundance of fatty acids, amino acids, organic acids, vitamins, and minerals, which can reduce the risk of many chronic diseases. LC-MS/MS screening identified 69 and 103 compounds in spinach and kale, respectively, including flavonoids, glucosinolates, and phenolic and organic acids. Out of a total of 26 flavonoids identified in the current study, only three were found in spinach. All three leafy greens showed nutritional and health benefits and the unique phytochemical compounds found only in purslane provide a strong basis to incorporate its distinct dietary benefits.
Provided by the author(s) and NUI Galway in accordance with publisher policies. Please cite the p... more Provided by the author(s) and NUI Galway in accordance with publisher policies. Please cite the published version when available. Downloaded 2016-05-17T05:32:42Z Some rights reserved. For more information, please see the item record link above.
Coffee cherry is a rich source of chlorogenic acids (CGAs) and caffeine. In this study we examine... more Coffee cherry is a rich source of chlorogenic acids (CGAs) and caffeine. In this study we examined the potential antioxidant activity and enzyme inhibitory effects of whole coffee cherries (WCC) and their two extracts on α-amylase, α-glucosidase and acetylcholinesterase (AChE) activities, which are targets for the control of diabetes and Alzheimer’s diseases. Whole coffee cherry extract 40% (WCCE1) is rich in chlorogenic acid compounds, consisting of a minimum of 40% major isomers, namely 3-caffeoylquinic acids, 4-caffeoylquinic acids, 5-caffeoylquinic acids, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, 4-feruloylquinc acid, and 5-feruloylquinc acid. Whole coffee cherry extract 70% (WCCE2) is rich in caffeine, with a minimum of 70%. WCCE1 inhibited the activities of digestive enzymes α-amylase and α-glucosidase, and WCCE2 inhibited acetylcholinesterase activities with their IC50 values of 1.74, 2.42, and 0.09 mg/mL, respectively. Multiple antioxid...
Proceedings of the National Academy of Sciences, 2018
Significance Double-strand breaks (DSBs) in the DNA are the most dangerous type of damage and mus... more Significance Double-strand breaks (DSBs) in the DNA are the most dangerous type of damage and must be repaired to maintain genome integrity, avoiding disease-linked mutations and cancer initiation/progression. The NuA4 histone acetyltransferase complex is recruited to DNA DSBs to facilitate repair through modification of the chromatin surrounding the damage, but its recruitment mechanism is poorly understood. Here, we report that the DNA damage sensor complex Mre11-Rad50-Xrs2 physically recruits NuA4 to the break sites followed by bidirectional spreading linked to the DNA end resection required for error-free repair by homologous recombination. During that process, NuA4 can acetylate ssDNA-binding replication protein A (RPA), leading to its displacement.
Histone deacetylases (HDACs) catalyze the removal of acetylation marks from lysine residues on hi... more Histone deacetylases (HDACs) catalyze the removal of acetylation marks from lysine residues on histone and nonhistone substrates. Their activity is generally associated with essential cellular processes such as transcriptional repression and heterochromatin formation. Interestingly, abnormal activity of HDACs has been reported in various types of cancers, which makes them a promising therapeutic target for cancer treatment. In the current study, we aim to understand the mechanisms underlying the function of HDACs using an in-depth quantitative analysis of changes in histone acetylation levels in Schizosaccharomyces pombe (S. pombe) lacking major HDAC activities. We employed a targeted quantitative mass spectrometry approach to profile changes of acetylation and methylation at multiple lysine residues on the N-terminal tail of histones H3 and H4. Our analyses identified a number of histone acetylation sites that are significantly affected by S. pombe HDAC mutations. We discovered that mutation of the Class I HDAC known as Clr6 causes a major increase in the abundance of triacetylated H4 molecules at K5, K8, and K12. A clr6-1 hypomorphic mutation also increased the abundance of multiple acetyl-lysines in histone H3. In addition, our study uncovered a few crosstalks between histone acetylation and methylation upon deletion of HDACs Hos2 and Clr3. We anticipate that the results from this study will greatly improve our current understanding of the mechanisms involved in HDAC-mediated gene regulation and heterochromatin assembly.
In Saccharomyces cerevisiae, histone H3 lysine 56 acetylation (H3K56Ac) is present in newly synth... more In Saccharomyces cerevisiae, histone H3 lysine 56 acetylation (H3K56Ac) is present in newly synthesized histones deposited throughout the genome during DNA replication. The sirtuins Hst3 and Hst4 deacetylate H3K56 after S-phase, and virtually all histone H3 molecules are K56-acetylated throughout the cell cycle in hst3∆ hst4∆ mutants. Failure to deacetylate H3K56 causes thermosensitivity, spontaneous DNA damage, and sensitivity to replicative stress via molecular mechanisms that remain unclear. Here we demonstrate that, unlike wild-type cells, hst3∆ hst4∆ cells are unable to complete genome duplication and accumulate persistent foci containing the homologous recombination protein Rad52 after exposure to genotoxic drugs during S-phase. In response to replicative stress, cells lacking Hst3 and Hst4 also displayed intense foci containing the Rfa1 subunit of the single-stranded DNA binding protein complex RPA, as well as persistent activation of DNA damage-induced kinases. To investigat...
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