Publications by authors named "A R Hippen"

65 Publications

Expanding and Remixing the Metadata Landscape.

Trends Cancer 2021 Apr 20;7(4):276-278. Epub 2020 Nov 20.

Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Childhood Cancer Data Lab, Alex's Lemonade Stand Foundation, Philadelphia, PA, USA. Electronic address:

Genomic data sharing accelerates research. Data are most valuable when they are accompanied by detailed metadata. To date, metadata are often human-annotated descriptions of samples and their handling. We discuss how machine learning-derived elements complement such descriptions to enhance the research ecosystem around genomic data.
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http://dx.doi.org/10.1016/j.trecan.2020.10.011DOI Listing
April 2021

Infusion of butyrate affects plasma glucose, butyrate, and β-hydroxybutyrate but not plasma insulin in lactating dairy cows.

J Dairy Sci 2018 Apr 1;101(4):3524-3536. Epub 2018 Mar 1.

GANS Inc., 24 Av. De la Guillemotte, 78112 Fourqueux, France.

The objective of this study was to investigate the effects on plasma metabolites and rumen traits when butyrate was infused into the rumen or abomasum of lactating cows. Jugular catheters were inserted into 5 ruminally fistulated Holstein cows [94.2 ± 26.3 DIM; 717 ± 45 kg of body weight (BW); mean ± SD] in a 5 × 5 Latin square with 3-d periods. Cows were infused for 24 h with 1 of 5 treatments: water (CON), 1 g/kg of BW of butyrate infused into either the abomasum (A1) or rumen (R1), or 2 g/kg of BW of butyrate infused into either the abomasum or rumen. Sodium butyrate was the source of butyrate and NaCl was added to the CON, A1, and R1 treatments to provide the same amount of sodium as supplied by the sodium butyrate treatment in the 2-g treatments. Plastisol flanges were inserted into the abomasum to allow infusion to the abomasum and peristaltic pumps provided continuous infusion at 9.3 mL/min for all treatments. The concentration of NaCl and sodium butyrate was varied in the infusate to provide the correct infusion amount. Rumen fluid samples were collected at -2, -1, 0, 1, 2, 3, 4, 6, 8, 12, 18, 24, 28, and 32 h relative to start of infusion. Serial blood samples were collected at -2, -1, 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 26, 28, and 32 h relative to start of infusion. Compared with CON, infusing butyrate increased both plasma butyrate and plasma β-hydroxybutyrate (BHB), whereas plasma glucose decreased. Increasing butyrate infusion from 1 to 2 g increased plasma butyrate, tended to decrease plasma glucose, and tended to increase plasma BHB. Compared with abomasal infusion, rumen infusion of butyrate increased rumen butyrate, did not affect plasma glucose, and tended to increase plasma BHB. Treatment had no effect on plasma insulin. Results demonstrated that site of infusion and amount of butyrate affected several plasma metabolites when butyrate was infused in lactating dairy cows over a period of 24 h.
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http://dx.doi.org/10.3168/jds.2017-13842DOI Listing
April 2018

Single-dose infusion of sodium butyrate, but not lactose, increases plasma β-hydroxybutyrate and insulin in lactating dairy cows.

J Dairy Sci 2017 Jan 9;100(1):757-768. Epub 2016 Nov 9.

GANS Inc., 24 Av. De la Guillemotte, 78112 Fourqueux, France.

Several studies have identified beneficial effects of butyrate on rumen development and intestinal health in preruminants. These encouraging findings led to further investigations related to butyrate supplementation in the mature ruminant. However, the effects of elevated butyrate concentrations on rumen metabolism have not been investigated, and consequently the maximum tolerable dosage rate of butyrate has not been established. Therefore, the first objective of this work was to evaluate the effect of a short-term increase in rumen butyrate concentration on key metabolic indicators. The second objective was to evaluate the source of butyrate, either directly dosed in the rumen or indirectly supplied via lactose fermentation in the rumen. Jugular catheters were inserted into 4 ruminally fistulated Holstein cows in a 4×4 Latin square with 3-d periods. On d 1 of each period, 1h after feeding, cows were ruminally dosed with 1 of 4 treatments: (1) 2L of water (CON), (2) 3.5g/kg of body weight (BW) of lactose (LAC), (3) 1g/kg of BW of butyrate (1GB), or (4) 2g/kg of BW of butyrate (2GB). Sodium butyrate was the source of butyrate, and NaCl was added to CON (1.34g/kg of BW), LAC (1.34g/kg of BW), and 1GB (0.67g/kg of BW) to provide equal amounts of sodium as the 2GB treatment. Serial plasma and rumen fluid samples were collected during d 1 of each period. Rumen fluid pH was greater in cows given the 1GB and 2GB treatments compared with the cows given the LAC treatment. Cows administered the 1GB and 2GB treatments had greater rumen butyrate concentrations compared with LAC. Those cows also had greater plasma butyrate concentrations compared with cows given the LAC treatment. Plasma β-hydroxybutyrate was greater and insulin tended to be greater for butyrate treatments compared with LAC. No difference in insulin was found between the 1GB and 2GB treatments. Based on plasma and rumen metabolites, singly infusing 3.5g/kg of BW of lactose into the rumen is not as effective at providing a source of butyrate as compared with singly infusing 1 or 2g/kg of BW of butyrate into the rumen. Additionally, rumen pH, rumen butyrate, plasma β-hydroxybutyrate, glucose, and plasma butyrate were less affected in cows administered the 1GB treatment than in cows given the 2GB treatment. This finding suggests that singly dosing 1g/kg of BW of butyrate could serve as the maximum tolerable concentration for future research.
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http://dx.doi.org/10.3168/jds.2016-11634DOI Listing
January 2017

Presenilin E318G variant and Alzheimer's disease risk: the Cache County study.

BMC Genomics 2016 06 29;17 Suppl 3:438. Epub 2016 Jun 29.

Department of Biology, Brigham Young University, Provo, UT, USA.

Background: Alzheimer's disease is the leading cause of dementia in the elderly and the third most common cause of death in the United States. A vast number of genes regulate Alzheimer's disease, including Presenilin 1 (PSEN1). Multiple studies have attempted to locate novel variants in the PSEN1 gene that affect Alzheimer's disease status. A recent study suggested that one of these variants, PSEN1 E318G (rs17125721), significantly affects Alzheimer's disease status in a large case-control dataset, particularly in connection with the APOEε4 allele.

Methods: Our study looks at the same variant in the Cache County Study on Memory and Aging, a large population-based dataset. We tested for association between E318G genotype and Alzheimer's disease status by running a series of Fisher's exact tests. We also performed logistic regression to test for an additive effect of E318G genotype on Alzheimer's disease status and for the existence of an interaction between E318G and APOEε4.

Results: In our Fisher's exact test, it appeared that APOEε4 carriers with an E318G allele have slightly higher risk for AD than those without the allele (3.3 vs. 3.8); however, the 95 % confidence intervals of those estimates overlapped completely, indicating non-significance. Our logistic regression model found a positive but non-significant main effect for E318G (p = 0.895). The interaction term between E318G and APOEε4 was also non-significant (p = 0.689).

Conclusions: Our findings do not provide significant support for E318G as a risk factor for AD in APOEε4 carriers. Our calculations indicated that the overall sample used in the logistic regression models was adequately powered to detect the sort of effect sizes observed previously. However, the power analyses of our Fisher's exact tests indicate that our partitioned data was underpowered, particularly in regards to the low number of E318G carriers, both AD cases and controls, in the Cache county dataset. Thus, the differences in types of datasets used may help to explain the difference in effect magnitudes seen. Analyses in additional case-control datasets will be required to understand fully the effect of E318G on Alzheimer's disease status.
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http://dx.doi.org/10.1186/s12864-016-2786-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4943516PMC
June 2016