Publications by authors named "Rachel L Adams"

9 Publications

  • Page 1 of 1

Patterns of stress generation differ depending on internalizing symptoms, alcohol use, and personality traits in early adulthood: a five year longitudinal study.

Anxiety Stress Coping 2021 Apr 5:1-14. Epub 2021 Apr 5.

Public Health Sciences, University of Connecticut School of Medicine, Farmington, USA.

Background: Depression is thought to generate stressful life events. However, other internalizing symptoms such as anxiety or post-traumatic stress and individual difference variables such as personality traits and alcohol use may contribute to stressful life events. Whether stress generation is specific to depression or generalized to these other variables is unclear. Therefore, we tested whether stress generation was depression specific or generalizable to anxiety, PTSD, alcohol use, neuroticism, and extraversion.

Design: Two-wave longitudinal study with a five-year follow-up.

Methods: 917 young adults completed measures of internalizing symptoms, alcohol use, neuroticism, and extraversion during college and five years later along with an interview-based measure of life events.

Results: Symptoms of depression, anxiety, PTSD, and neuroticism exhibited bivariate predictive effects on interpersonal-dependent events. When considering internalizing symptoms in the aggregate, stress generation was specific to symptoms rather than neuroticism. Furthermore, interpersonal-dependent life events mediated Time 1 internalizing symptoms predicting Time 2 symptoms.

Conclusion: Our results indicate that stress generation applies to internalizing symptoms broadly rather than specifically to depression. Moreover, neuroticism was no longer a significant predictor of life events when examined with internalizing symptoms simultaneously. These results support the value of integrative models that test numerous factors predicting stressful life events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10615806.2021.1910677DOI Listing
April 2021

The vitamin A ester retinyl propionate has a unique metabolic profile and higher retinoid-related bioactivity over retinol and retinyl palmitate in human skin models.

Exp Dermatol 2021 Feb 5;30(2):226-236. Epub 2020 Nov 5.

The Procter and Gamble Company, Cincinnati, OH, USA.

Human skin is exposed daily to environmental stressors, which cause acute damage and inflammation. Over time, this leads to morphological and visual appearance changes associated with premature ageing. Topical vitamin A derivatives such as retinol (ROL), retinyl palmitate (RPalm) and retinyl propionate (RP) have been used to reverse these changes and improve the appearance of skin. This study investigated a stoichiometric comparison of these retinoids using in vitro and ex vivo skin models. Skin biopsies were treated topically to compare skin penetration and metabolism. Treated keratinocytes were evaluated for transcriptomics profiling and hyaluronic acid (HA) synthesis and treated 3D epidermal skin equivalents were stained for epidermal thickness, Ki67 and filaggrin. A retinoic acid receptor-alpha (RARα) reporter cell line was used to compare retinoid activation levels. Results from ex vivo skin found that RP and ROL have higher penetration levels compared with RPalm. RP is metabolized primarily into ROL in the viable epidermis and dermis whereas ROL is esterified into RPalm and metabolized into the inactive retinoid 14-hydroxy-4,14-retro-retinol (14-HRR). RP treatment yielded higher RARα activation and HA synthesis levels than ROL whereas RPalm had a null effect. In keratinocytes, RP and ROL stimulated similar gene expression patterns and pathway theme profiles. In conclusion, RP and ROL show a similar response directionality whereas RPalm response was inconsistent. Additionally, RP has a consistently higher magnitude of response compared with ROL or RPalm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/exd.14219DOI Listing
February 2021

Deficiency of Natriuretic Peptide Receptor 2 Promotes Bicuspid Aortic Valves, Aortic Valve Disease, Left Ventricular Dysfunction, and Ascending Aortic Dilatations in Mice.

Circ Res 2018 02 22;122(3):405-416. Epub 2017 Dec 22.

From the Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada (M.C.B., R.L.E.A., Y.-Q.Z., L.-l.C., Z.M., A.Y.-L.L., R.K.K.T., H.Z., S.P.H., C.A.S.); Institute of Biomaterials and Biomedical Engineering (M.C.B., K.W., R.L.E.A., A.Y.-L.L., R.K.K.T., C.A.S.), Department of Physiology (H.Z., S.P.H.), and Department of Mechanical and Industrial Engineering (L.-l.C., Z.M., C.A.S.), University of Toronto, Ontario, Canada; and Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada (Y.-Q.Z., R.M.H.).

Rationale: Aortic valve disease is a cell-mediated process without effective pharmacotherapy. CNP (C-type natriuretic peptide) inhibits myofibrogenesis and osteogenesis of cultured valve interstitial cells and is downregulated in stenotic aortic valves. However, it is unknown whether CNP signaling regulates aortic valve health in vivo.

Objective: The aim of this study is to determine whether a deficient CNP signaling axis in mice causes accelerated progression of aortic valve disease.

Methods And Results: In cultured porcine valve interstitial cells, CNP inhibited pathological differentiation via the guanylate cyclase NPR2 (natriuretic peptide receptor 2) and not the G-protein-coupled clearance receptor NPR3 (natriuretic peptide receptor 3). We used and ; mice and wild-type littermate controls to examine the valvular effects of deficient CNP/NPR2 signaling in vivo, in the context of both moderate and advanced aortic valve disease. Myofibrogenesis in cultured fibroblasts was insensitive to CNP treatment, whereas aged and ;-/- mice developed cardiac dysfunction and ventricular fibrosis. Aortic valve function was significantly impaired in and ; mice versus wild-type littermates, with increased valve thickening, myofibrogenesis, osteogenesis, proteoglycan synthesis, collagen accumulation, and calcification. 9.4% of mice heterozygous for had congenital bicuspid aortic valves, with worse aortic valve function, fibrosis, and calcification than those with typical tricuspid aortic valves or all wild-type littermate controls. Moreover, cGK (cGMP-dependent protein kinase) activity was downregulated in valves, and CNP triggered synthesis of cGMP and activation of cGK1 (cGMP-dependent protein kinase 1) in cultured porcine valve interstitial cells. Finally, aged ; mice developed dilatation of the ascending aortic, with greater aneurysmal progression in mice with bicuspid aortic valves than those with tricuspid valves.

Conclusions: Our data establish CNP/NPR2 signaling as a novel regulator of aortic valve development and disease and elucidate the therapeutic potential of targeting this pathway to arrest disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCRESAHA.117.311194DOI Listing
February 2018

Insulinotropic Effects of Whey: Mechanisms of Action, Recent Clinical Trials, and Clinical Applications.

Ann Nutr Metab 2016 17;69(1):56-63. Epub 2016 Aug 17.

Department of Nutrition and Food Science, Texas Woman's University, Denton, Tex., USA.

Background: The insulinotropic effect of whey protein is not fully understood and has clinical implications in the regulation of chronic and acute hyperglycemia.

Summary: This review describes the composition of whey protein and potential mechanisms through which whey exerts an insulinotropic effect, including increasing the gastric emptying rate, effect on incretin hormones particularly gastric inhibitory peptide and glucagon-like polypeptide-1, and whey's role as a dipeptidyl peptidase IV inhibitor. Recent clinical evidence on the use of whey protein concentrate, isolate and hydrolysate in the management of type 2 diabetes and in the acute care adult population is reviewed.

Key Messages: The mechanism through which whey protein exerts its insulinotropic effect is multifactorial. Increasing evidence supports the potential use of whey protein in medical/nutritional therapy to manage glycemia; however, additional research is needed to determine the most appropriate dose, form and delivery method for whey supplementation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000448665DOI Listing
January 2018

Grouping 34 Chemicals Based on Mode of Action Using Connectivity Mapping.

Toxicol Sci 2016 06 29;151(2):447-61. Epub 2016 Mar 29.

*Mason Business Center, The Procter & Gamble Company, Cincinnati, Ohio 45040 and.

Connectivity mapping is a method used in the pharmaceutical industry to find connections between small molecules, disease states, and genes. The concept can be applied to a predictive toxicology paradigm to find connections between chemicals, adverse events, and genes. In order to assess the applicability of the technique for predictive toxicology purposes, we performed gene array experiments on 34 different chemicals: bisphenol A, genistein, ethinyl-estradiol, tamoxifen, clofibrate, dehydorepiandrosterone, troglitazone, diethylhexyl phthalate, flutamide, trenbolone, phenobarbital, retinoic acid, thyroxine, 1α,25-dihydroxyvitamin D3, clobetasol, farnesol, chenodeoxycholic acid, progesterone, RU486, ketoconazole, valproic acid, desferrioxamine, amoxicillin, 6-aminonicotinamide, metformin, phenformin, methotrexate, vinblastine, ANIT (1-naphthyl isothiocyanate), griseofulvin, nicotine, imidacloprid, vorinostat, 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) at the 6-, 24-, and 48-hour time points for 3 different concentrations in the 4 cell lines: MCF7, Ishikawa, HepaRG, and HepG2 GEO (super series accession no.: GSE69851). The 34 chemicals were grouped in to predefined mode of action (MOA)-based chemical classes based on current literature. Connectivity mapping was used to find linkages between each chemical and between chemical classes. Cell line-specific linkages were compared with each other and to test whether the method was platform and user independent, a similar analysis was performed against publicly available data. The study showed that the method can group chemicals based on MOAs and the inter-chemical class comparison alluded to connections between MOAs that were not predefined. Comparison to the publicly available data showed that the method is user and platform independent. The results provide an example of an alternate data analysis process for high-content data, beneficial for predictive toxicology, especially when grouping chemicals for read across purposes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/toxsci/kfw058DOI Listing
June 2016

A novel transcriptomics based in vitro method to compare and predict hepatotoxicity based on mode of action.

Toxicology 2015 Feb 2;328:29-39. Epub 2014 Dec 2.

Mason Business Center, The Procter & Gamble Company, Cincinnati, OH 45040, USA.

High-content data have the potential to inform mechanism of action for toxicants. However, most data to support this notion have been generated in vivo. Because many cell lines and primary cells maintain a differentiated cell phenotype, it is possible that cells grown in culture may also be useful in predictive toxicology via high-content approaches such as whole-genome microarray. We evaluated global changes in gene expression in primary rat hepatocytes exposed to two concentrations of ten hepatotoxicants: acetaminophen (APAP), β-naphthoflavone (BNF), chlorpromazine (CPZ), clofibrate (CLO), bis(2-ethylhexyl)phthalate (DEHP), diisononyl phthalate (DINP), methapyrilene (MP), valproic acid (VPA), phenobarbital (PB) and WY14643 at two separate time points. These compounds were selected to cover a range of mechanisms of toxicity, with some overlap in expected mechanism to address the question of how predictive gene expression analysis is, for a given mode of action. Gene expression microarray analysis was performed on cells after 24h and 48h of exposure to each chemical using Affymetrix microarrays. Cluster analysis suggests that the primary hepatocyte model was capable of responding to these hepatotoxicants, with changes in gene expression that appear to be mode of action-specific. Among the different methods used for analysis of the data, a combination method that used pathways (MOAs) to filter total probesets provided the most robust analysis. The analysis resulted in the phthalates clustering closely together, with the two other peroxisome proliferators, CLO and WY14643, eliciting similar responses at the whole-genome and pathway levels. The Cyp inducers PB, MP, CPZ and BNF also clustered together. VPA and APAP had profiles that were unique. A similar analysis was performed on externally available (TG-GATES) in vivo data for 6 of the chemicals (APAP, CLO, CPZ, MP, MP and WY14643) and compared to the in vitro result. These results indicate that transcription profiling using an in vitro assay may offer pertinent biological data to support predictions of in vivo hepatotoxicity potential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tox.2014.11.008DOI Listing
February 2015

Drosophila melanogaster p24 trafficking proteins have vital roles in development and reproduction.

Mech Dev 2012 Jul 24;129(5-8):177-91. Epub 2012 Apr 24.

Department of Biology, Texas A&M University, College Station, TX 77843-3258, USA.

p24 proteins comprise a family of type-I transmembrane proteins of ~24kD that are present in yeast and plants as well as metazoans ranging from Drosophila to humans. These proteins are most commonly localized to the endoplasmic reticulum (ER)-Golgi interface and are incorporated in anterograde and retrograde transport vesicles. Little is known about how disruption of p24 signaling affects individual tissue function or whole animals. Drosophila melanogaster express nine p24 genes, grouped into four subfamilies. Based upon our mRNA and protein expression data, Drosophila p24 family members are expressed in a variety of tissues. To identify functions for particular Drosophila p24 proteins, we used RNA interference (RNAi) to reduce p24 expression. Ubiquitous reduction of most p24 genes resulted in complete or partial lethality during development. We found that reducing p24 levels in adults caused defects in female fecundity (egg laying) and also reduced male fertility. We attributed reduced female fecundity to decreased neural p24 expression. These results provide the first genetic analysis of all p24 family members in a multicellular animal and indicate vital roles for Drosophila p24s in development and reproduction, implicating neural expression of p24s in the regulation of female behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mod.2012.04.002DOI Listing
July 2012

Ex situ bioremediation of phenol contaminated soil using polymer beads.

Biotechnol Lett 2006 Dec 29;28(24):2027-31. Epub 2006 Sep 29.

Department of Chemical Engineering, Queen's University, Kingston, Ontario, K7L 3N6, Canada.

Polymer beads have been used to absorb high concentrations of phenol from soil decreasing the initial concentration of 2.3 g kg(-1) soil to 100 mg kg(-1) soil and achieving a phenol loading within the polymer beads of 27.5 mg phenol g(-1) beads. The phenol-loaded polymer beads were removed from the soil and placed in a bioreactor, which was then inoculated with a phenol-degrading microbial consortium. All of the phenol contained within the polymer beads was shown to desorb from the polymer matrix and was degraded by the microbial consortium. The beads were used again (twice) in a similar manner with no loss in performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10529-006-9189-1DOI Listing
December 2006

The interaction of disulfide flavor compounds with proteins in model systems.

Adv Exp Med Biol 2004 ;542:147-53

The University of Reading, School of Food Biosciences, Whiteknights, Reading RG6 6AP, United Kingdom.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-4419-9090-7_9DOI Listing
June 2004