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Search Results: 1 - 10 of 227115 matches for " Dennis R Petersen "
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The human protein disulfide isomerase gene family
James J Galligan, Dennis R Petersen
Human Genomics , 2012, DOI: 10.1186/1479-7364-6-6
The human fatty acid-binding protein family: Evolutionary divergences and functions
Rebecca L Smathers, Dennis R Petersen
Human Genomics , 2011, DOI: 10.1186/1479-7364-5-3-170
Abstract: Hydrophobic ligands, such as fatty acids (FAs) and their acyl-CoA derivatives (FA-CoA), serve many biological functions within the cell. They serve as metabolic energy sources, substrates for membranes and signalling molecules for metabolic regulation [1,2]. The insoluble properties of FAs make for the requirement for chaperones to bind and transfer them throughout various cellular compartments, including the peroxisomes, mitochondria, endoplasmic reticulum, lipid droplets and nucleus. A family of highly expressed intracellular lipid-binding proteins (iLBPs)--the fatty acid-binding proteins (FABPs)--serves to bind these free ligands with high affinity. FABPs are ubiquitously expressed throughout tissues that are highly active in FA metabolism and comprise several isoforms. To date, nine FABP protein-coding genes have been identified in the human genome. These include liver(L-FABP), intestine- (I-FABP), heart- (H-FABP), adipocyte- (A-FABP), epidermal- (E-FABP), ileal-(Il-FABP), brain- (B-FABP), myelin- (M-FABP) and testis-FABP (T-FABP). These different isoforms were first named for the organ in which they were first identified or mostly predominate, but their expression profiles are not exclusive to that specific organ. For example, L-FABP is not only expressed in the liver, but also in the intestine, pancreas, kidney, lung and stomach. In addition to the nine known FABPs that have been widely studied, a newer member of the family, FABP12, has recently been discovered. The gene has been identified, but published reports on the protein encoded by this gene are not yet available. Therefore, in this reviews only the identification of the gene will be addressed.Although members of the FABP family share moderate sequence homologies of 20-70 per cent, their tertiary structures are virtually superimposable [3-5]. Sequences of human FABPs are aligned in Figure 1. These ~15-kilodalton proteins comprise ten anti-parallel β-barrel (βA-βJ) structures containing a solvent-accessi
The human sirtuin family: Evolutionary divergences and functions
Athanassios Vassilopoulos, Kristofer S Fritz, Dennis R Petersen, David Gius
Human Genomics , 2011, DOI: 10.1186/1479-7364-5-5-485
Abstract: Epigenetic modifications of protein, histone and chromatin play an important role in regulating gene expression, cancer formation and life span. Acetylation is a major player in epigenetic modifications, resulting in open chromatin structures and, hence, permissive conditions for transcription-factor recruitment to the promoters, followed by initiation of transcription. By contrast, histone deacetylases (HDACs) oppose the activity of histone acetyltransferases by removing the acetyl groups from lysine residues within specific promoters, leading to gene silencing [1]. In addition, many non-histone proteins have been identified as substrates of HDACs, implicating acetylation as a post-translational modification that affects various aspects of cell physiology [2]. There are two protein families having HDAC activity: the classical HDAC family, which consists of two different phylogenetic classes (class I and class II); and the sirtuin family of proteins, which requires the co-factor nicotinamide adenine dinucleotide (NAD) for its deacetylase activity [3,4].The sirtuin family of proteins is highly conserved, both functionally and structurally. Its members are integrated into most forms of life, including eubacteria, archaea and eukaryotes, and therefore predate both histone and chromatin formation [5]. Sirtuins have been involved in metabolic and chromatin regulation throughout evolution, dating back to the first examples of chromatin-like organisation of DNA in archaea [6,7]. The silent information regulator 2 gene (Sir2) was first discovered in Saccharomyces cerevisiae and was named after its ability to relieve gene silencing [8]. Once discovered, sirtuins were rapidly characterised in yeast, bacteria, plants and mammals.Sirtuins belong to the deoxyhypusine synthase (DHS)-like NAD/flavin adenine dinucleotide (FAD)-binding domain clan and all members contain the Rossmann fold structural motif, which can be found in proteins that bind nucleotides. The other members of th
Ethanol Metabolism Modifies Hepatic Protein Acylation in Mice
Kristofer S. Fritz, Michelle F. Green, Dennis R. Petersen, Matthew D. Hirschey
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075868
Abstract: Mitochondrial protein acetylation increases in response to chronic ethanol ingestion in mice, and is thought to reduce mitochondrial function and contribute to the pathogenesis of alcoholic liver disease. The mitochondrial deacetylase SIRT3 regulates the acetylation status of several mitochondrial proteins, including those involved in ethanol metabolism. The newly discovered desuccinylase activity of the mitochondrial sirtuin SIRT5 suggests that protein succinylation could be an important post-translational modification regulating mitochondrial metabolism. To assess the possible role of protein succinylation in ethanol metabolism, we surveyed hepatic sub-cellular protein fractions from mice fed a control or ethanol-supplemented diet for succinyl-lysine, as well as acetyl-, propionyl-, and butyryl-lysine post-translational modifications. We found mitochondrial protein propionylation increases, similar to mitochondrial protein acetylation. In contrast, mitochondrial protein succinylation is reduced. These mitochondrial protein modifications appear to be primarily driven by ethanol metabolism, and not by changes in mitochondrial sirtuin levels. Similar trends in acyl modifications were observed in the nucleus. However, comparatively fewer acyl modifications were observed in the cytoplasmic or the microsomal compartments, and were generally unchanged by ethanol metabolism. Using a mass spectrometry proteomics approach, we identified several candidate acetylated, propionylated, and succinylated proteins, which were enriched using antibodies against each modification. Additionally, we identified several acetyl and propionyl lysine residues on the same sites for a number of proteins and supports the idea of the overlapping nature of lysine-specific acylation. Thus, we show that novel post-translational modifications are present in hepatic mitochondrial, nuclear, cytoplasmic, and microsomal compartments and ethanol ingestion, and its associated metabolism, induce specific changes in these acyl modifications. These data suggest that protein acylation, beyond protein acetylation, contributes to the overall metabolic regulatory network and could play an important role in the pathogenesis of alcoholic liver disease.
Characterization of 4-HNE Modified L-FABP Reveals Alterations in Structural and Functional Dynamics
Rebecca L. Smathers, Kristofer S. Fritz, James J. Galligan, Colin T. Shearn, Philip Reigan, Michael J. Marks, Dennis R. Petersen
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0038459
Abstract: 4-Hydroxynonenal (4-HNE) is a reactive α,β-unsaturated aldehyde produced during oxidative stress and subsequent lipid peroxidation of polyunsaturated fatty acids. The reactivity of 4-HNE towards DNA and nucleophilic amino acids has been well established. In this report, using proteomic approaches, liver fatty acid-binding protein (L-FABP) is identified as a target for modification by 4-HNE. This lipid binding protein mediates the uptake and trafficking of hydrophobic ligands throughout cellular compartments. Ethanol caused a significant decrease in L-FABP protein (P<0.001) and mRNA (P<0.05), as well as increased poly-ubiquitinated L-FABP (P<0.001). Sites of 4-HNE adduction on mouse recombinant L-FABP were mapped using MALDI-TOF/TOF mass spectrometry on apo (Lys57 and Cys69) and holo (Lys6, Lys31, His43, Lys46, Lys57 and Cys69) L-FABP. The impact of 4-HNE adduction was found to occur in a concentration-dependent manner; affinity for the fluorescent ligand, anilinonaphthalene-8-sulfonic acid, was reduced from 0.347 μM to Kd1 = 0.395 μM and Kd2 = 34.20 μM. Saturation analyses revealed that capacity for ligand is reduced by approximately 50% when adducted by 4-HNE. Thermal stability curves of apo L-FABP was also found to be significantly affected by 4-HNE adduction (ΔTm = 5.44°C, P<0.01). Computational-based molecular modeling simulations of adducted protein revealed minor conformational changes in global protein structure of apo and holo L-FABP while more apparent differences were observed within the internal binding pocket, revealing reduced area and structural integrity. New solvent accessible portals on the periphery of the protein were observed following 4-HNE modification in both the apo and holo state, suggesting an adaptive response to carbonylation. The results from this study detail the dynamic process associated with L-FABP modification by 4-HNE and provide insight as to how alterations in structural integrity and ligand binding may a contributing factor in the pathogenesis of ALD.
A General Framework For Determining the Temporal and Evolutionary Dynamics of Religion-Based Website Popularity on the Internet  [PDF]
Michael R. Golinski, Connie Petersen
Open Journal of Statistics (OJS) , 2012, DOI: 10.4236/ojs.2012.24052
Abstract: Religion-based websites are fast becoming a major pipeline for disseminating religious information to broad populations of individuals in the United States.Both mainstream religions and fringe religions are easily accessible to a large population of internet users. The purpose of this review is to develop and examine a general framework that uses simple mathematical and statistical models to interpret and measure temporal ‘snap shots’ in the popularity of religious websites. We extend this framework to include an evolutionary model that has the potential to predict long-term shifts or changes in the popularity of religious websites over time. Ultimately, the goal of this review is to introduce a new modeling framework for research into how the internet is changing the accessibility and views of populations of individuals who follow various religions on the internet and how this may in-turn affect the distribution of religion in the ‘real world’.
Short Term Feeding of a High Fat Diet Exerts an Additive Effect on Hepatocellular Damage and Steatosis in Liver-Specific PTEN Knockout Mice
Colin T. Shearn, Kelly E. Mercer, David J. Orlicky, Leah Hennings, Rebecca L. Smathers-McCullough, Bangyan L. Stiles, Martin J. J. Ronis, Dennis R. Petersen
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096553
Abstract: Background Hepatospecific deletion of PTEN results in constitutive activation of Akt and increased lipogenesis. In mice, the addition of a high fat diet (HFD) downregulates lipogenesis. The aim of this study was to determine the effects of a HFD on hepatocellular damage induced by deletion of PTEN. Methods 12 Week old male flox/flox hepatospecific PTEN mice (PTENf/f) or Alb-Cre controls were fed a HFD composed of 45% fat-derived calories (from corn oil) or a normal chow. Animals were then analyzed for hepatocellular damage, oxidative stress and expression of enzymes involved in fatty acid metabolism. Results In the Alb-Cre animals, the addition of a HFD resulted in a significant increase in liver triglycerides and altered REDOX capacity as evidenced by increased GPX activity, decreased GST activity and decreased hepatic concentrations of GSSG. In addition, SCD2, ACLY and FASN were all downregulated by the addition of HFD. Furthermore, expression of PPARα and PPARα-dependent proteins Cyp4a and ACSL1 were upregulated. In the PTENf/f mice, HFD resulted in significant increased in ALT, serum triglycerides and decreased REDOX capacity. Although expression of fatty acid synthetic enzymes was elevated in the chow fed PTENf/f group, the addition of HFD resulted in SCD2, ACLY and FASN downregulation. Compared to the Alb-Cre HFD group, expression of PGC1α, PPARα and its downstream targets ACSL and Cyp4a were upregulated in PTENf/f mice. Conclusions These data suggest that during conditions of constitutive Akt activation and increased steatosis, the addition of a HFD enhances hepatocellular damage due to increased CD36 expression and altered REDOX status. In addition, this work indicates HFD-induced hepatocellular damage occurs in part, independently of Akt signaling.
Issues in Distribution Center Relocation  [PDF]
Charles G. Petersen, Gerald R. Aase
Open Journal of Business and Management (OJBM) , 2016, DOI: 10.4236/ojbm.2016.41002
Abstract: This paper examines distribution center relocation where a firm needs to move from a current distribution center to a new distribution center in a different location. The authors present a decision framework as well as a case study of a pharmaceutical distribution company that recently underwent a distribution center relocation. One of the major factors in determining how to accomplish this relocation is the customers’ service expectations especially if customers will not tolerate a disruption in deliveries or if they expect all product to be a single delivery. The capabilities of the firm to handle operate both distribution centers simultaneously is another consideration. Lastly, firms need to determine the cost of the relocation including transportation, inventory, and additional picking costs.
Improving Order Picking Efficiency with the Use of Cross Aisles and Storage Policies  [PDF]
Charles G. Petersen, Gerald R. Aase
Open Journal of Business and Management (OJBM) , 2017, DOI: 10.4236/ojbm.2017.51009
Abstract: Order picking operations need to efficiently process orders in today’s competitive environment. Previous research generally assumed on even placement of the cross aisles. This research examines the placement of cross aisles in order picking operations and its effect on various storage policies. While previous research has primarily examined cross aisles and storage policies separately, this research looks at them simultaneously. The results showed no difference between even and uneven placement of cross aisles and that within-aisle storage is better than across-aisle and random storage. The results also showed that within-aisle storage provides greater travel distance savings than the use of cross aisles.
Climate change vulnerability index for South African aquifers
I Dennis, R Dennis
Water SA , 2012,
Abstract: South Africa is viewed as a water-stressed country with an average annual rainfall of 500 mm and any climatic change could have adverse impacts on water resources of the country. The potential impacts of climate change on water resources and surface hydrology for Africa and Southern Africa have received considerable attention from hydrologists during the past decade. Very little research has been conducted on the future impact of climate change on groundwater resources in South Africa. Climate change can affect groundwater levels, recharge and groundwater contribution to baseflow. To assess these impacts a climate change vulnerability index was developed. This vulnerability-index method is known as the DART index. The parameters considered in the DART method are as follows: depth to water-level change, aquifer type (storativity), recharge and transmissivity. The DART index is used as a regional screening tool to identify areas that could experience possible changes in their groundwater resources as a result of climate change. The current DART index does not account for adaptation and migration occurrences.
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