Publications by authors named "Elizabeth M Martin"

33 Publications

Using a Faculty-Developed Documentary-Style Film to Communicate Authentic Chemistry Research to a High School Audience.

J Chem Educ 2020 Aug 28;97(8):2351-2355. Epub 2020 Jul 28.

Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR.

Described is the creation, deployment, and evaluation of a video produced about the synthesis and applications of metal-organic frameworks (MOFs). The goal of this project was to gauge the impact of viewing the video on high school students' conceptions of authentic chemistry practices and applications. Additionally, comparisons were made between the use of the video and more traditional face-to-face presentations given by professional scientists. Observations, student surveys, and an interview with the high school chemistry teacher demonstrated the utility of such a video. Specifically, the students who viewed the video reported learning more about the nature of laboratory work in chemistry than other students who did not view the video. Students, regardless of whether they viewed the video or just received a presentation, reported growth in understandings of the applications of chemistry research and porous nanomaterial. Other research chemists are encouraged to consider ways that they could document on video the research that they are performing in order to introduce an untapped audience (high school students) to authentic chemistry research in a practically simple manner. During times of crisis, such as a pandemic, online videos could be a useful tool for high school chemistry teachers to use in collaboration with research faculty, particularly when schools are closed.
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http://dx.doi.org/10.1021/acs.jchemed.0c00376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329771PMC
August 2020

Directed movement toward, translocation along, penetration into and exit from vascular networks by breast cancer cells in 3D.

Cell Adh Migr 2021 Dec;15(1):224-248

Developmental Studies Hybridoma Bank and W.M. Keck Dynamic Image Analysis Facility, Department of Biology, The University of Iowa, Iowa City, IA, USA.

We developed a computer-assisted platform using laser scanning confocal microscopy to 3D reconstruct in real-time interactions between metastatic breast cancer cells and human umbilical vein endothelial cells (HUVECs). We demonstrate that MB-231 cancer cells migrate toward HUVEC networks, facilitated by filopodia, migrate along the network surfaces, penetrate into and migrate within the HUVEC networks, exit and continue migrating along network surfaces. The system is highly amenable to 3D reconstruction and computational analyses, and assessments of the effects of potential anti-metastasis monoclonal antibodies and other drugs. We demonstrate that an anti-RHAMM antibody blocks filopodium formation and all of the behaviors that we found take place between MB-231 cells and HUVEC networks.
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http://dx.doi.org/10.1080/19336918.2021.1957527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331046PMC
December 2021

The estrogen receptor/GATA3/FOXA1 transcriptional network: lessons learned from breast cancer.

Curr Opin Struct Biol 2021 Jul 2;71:65-70. Epub 2021 Jul 2.

Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, 111 TW Alexander Drive, NC, 27707, USA. Electronic address:

Cellular identity and physiologic function in mammary epithelial cells and in many breast cancers flow from the action of a network of master transcriptional regulators including estrogen receptor alpha, GATA3, and FOXA1. The last decade has seen the completion of multiple large sequencing projects focusing on breast cancer. These massive compendia of sequence data have provided a wealth of new information linking mutation in these transcription factors to alterations in tumor biology and transcriptional program. The emerging details on mutation in cancer, and direct experimental exploration of hypotheses based on it, are now providing a wealth of new information on the roles played by estrogen receptor alpha, GATA3, and FOXA1 in regulating gene transcription and how their combined action contributes to a network shaping cell function in both physiologic and disease states.
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http://dx.doi.org/10.1016/j.sbi.2021.05.015DOI Listing
July 2021

Environmental Factors Involved in Maternal Morbidity and Mortality.

J Womens Health (Larchmt) 2021 02 18;30(2):245-252. Epub 2020 Nov 18.

Office of Policy, Planning, and Evaluation, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, Durham, North Carolina, USA.

Nongenetic, environmental factors contribute to maternal morbidity and mortality through chemical exposures via air, water, soil, food, and consumer products. Pregnancy represents a particularly sensitive window of susceptibility during which physiological changes to every major organ system increase sensitivity to chemicals that can impact a woman's long-term health. Nonchemical stressors, such as low socioeconomic status, may exacerbate the effects of chemical exposures on maternal health. Racial/ethnic minorities are exposed disproportionately to both chemicals and nonchemical stressors, which likely contribute to the observed health disparities for maternal morbidities and mortality. Epidemiological studies linking exposures to adverse maternal health outcomes underscore the importance of environmental health impacts, and mechanistic studies in model systems reveal how chemicals perturb biological pathways and processes. Environmental stressors are associated with a variety of immediate maternal health impacts, including hypertensive disorders of pregnancy, fibroids, and infertility, as well as long-term maternal health impacts, such as higher risk of breast cancer and metabolic disorders. Identifying and reducing a pregnant woman's environmental exposures is not only beneficial to her offspring but also important to preserve her short- and long-term health.
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http://dx.doi.org/10.1089/jwh.2020.8855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891208PMC
February 2021

Physicochemical properties of soy protein hydrolysate and its formulation and stability with encapsulated probiotic under in vitro gastrointestinal environment.

J Food Sci 2020 Oct 31;85(10):3543-3551. Epub 2020 Aug 31.

Institute for Nanoscience and Engineering, University of Arkansas, 731 W. Dickson St., Fayetteville, AR, 72704, U.S.A.

The objective of this study was to prepare protein isolate from defatted soybean and identify an optimal hydrolysis protocol to create improved hydrolysates and ascertain the optimum encapsulation technique for probiotics. Soy protein isolate (SPI) was prepared using an alkaline extraction procedure for solubility within a neutral, beverage-specific pH range. The soy protein hydrolysate (SPH) was prepared from aqueous extracted SPI using pepsin. The physicochemical properties of the SPH were investigated by solubility, degree of hydrolysis (DH), surface hydrophobicity, and electrophoresis. Hydrolysates from 2, 2.5, and 3 hr of hydrolysis time achieved the suitable DH between 2.5% to 5.0%. The 2.5 to 3 hr hydrolysates were also significantly more soluble than SPI at all pH levels from 85% to 95% solubility. Surface hydrophobicity of the hydrolysates ranged from 15 to 20 S values. Alginate (1%), resistant starch (2%), and probiotic culture (0.1%) were used as an encapsulation agent to protect probiotics. Alginate microcapsules were observed to be 1 mm in size using environmental scanning electron microscopy. The dried SPH and encapsulated probiotics with alginate in a dry powder formulation were tested for its gastrointestinal resistance and probiotic viability under in vitro simulated digestion. Approximately 1-log decrease was observed for all experimental groups after simulated digestion (final log colony forming units [CFU]/mL range: 6.55 to 6.19) with free probiotics having the lowest log CFU/mL (6.10 ± 0.10) value. No significant difference was observed among experimental groups for probiotic viability (P = 0.445). The findings of this research will provide an understanding of formulation for easily digestible protein and encapsulated probiotics. PRACTICAL APPLICATION: The findings of this research provide an understanding of improved formulation for more suitable soy protein hydrolysate and viability of encapsulated probiotics in gastrointestinal environment. Probiotics with the prebiotics in an encapsulated environment provide a technology for the enhancement of probiotics viability and for applications in suitable products for health and wellness.
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http://dx.doi.org/10.1111/1750-3841.15399DOI Listing
October 2020

Evaluation of Bone Marrow Adipose Tissue and Bone Mineralization on Broiler Chickens Affected by Wooden Breast Myopathy.

Front Physiol 2019 29;10:674. Epub 2019 May 29.

Department of Poultry Science, University of Arkansas, Fayetteville, AR, United States.

In humans, alterations in bone metabolism have been associated with myopathies. We postulate the hypothesis that perhaps similar pathologies can also be associated in modern chickens. Hence, this study aimed to assess the fat infiltration in bone marrow and its repercussion on broiler chicken affected by Wooden Breast (WB) myopathy. Ten Cobb 500 live birds with extreme rigidity of the (PM) muscle were selected as WB affected chickens by physical examination of the muscle at 49 days of age, whereas ten chickens healthy with no physical signs of hardness in the breast muscle were considered to be unaffected. Macroscopic lesions in affected chickens included areas of firm and inflamed muscle with pale appearance, hemorrhaging, and viscous exudate on the surface. Bone marrow and sections of the PM muscle were collected and analyzed for light microscopy. Additionally, transmission electron microscopy was conducted in affected or unaffected muscle. Chickens affected with WB showed significant reductions ( < 0.05) in femur diameter, calcium, and phosphorous percentage but increased breast weight, compression force and filet thickness when compared with non-affected chickens. Interestingly, bone marrow from WB chicken had subjectively, more abundant infiltration of adipose tissue, when compared with non-affected chickens. Histology of the Pectoralis major of birds with WB showed abundant infiltration of adipose tissue, muscle fibers degeneration with necrosis and infiltration of heterophils and mononuclear cells, connective tissue proliferation, and vasculitis. Ultrastructural changes of WB muscle revealed lack definition of bands in muscle tissue, or any normal ultrastructural anatomy such as myofibrils. The endomysium components were necrotic, and in some areas, the endomysium was notable only as a string of necrotic tissue between degraded myofibrils. The fascia appeared hypertrophied, with large areas of necrosis and myofiber without structural identity with degraded mitochondria adjacent to the disrupted muscle tissue. As far as we know, this is the first study that describes a subjective increase in adipose tissue in the bone marrow of chickens affected with WB when compared with non-affected chickens, and reduced bone mineralization.
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http://dx.doi.org/10.3389/fphys.2019.00674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549442PMC
May 2019

Epigenome-wide DNA methylation in placentas from preterm infants: association with maternal socioeconomic status.

Epigenetics 2019 08 21;14(8):751-765. Epub 2019 May 21.

b Institute for Environmental Health Solutions, Gillings School of Global Public Health , University of North Carolina , Chapel Hill , NC , USA.

This study evaluated the hypothesis that prenatal maternal socioeconomic status (SES) adversity is associated with DNA methylation in the placenta. SES adversity was defined by the presence of, as well as a summative count of, four factors: less than college education, single marital status, food and nutritional service assistance, and public health insurance. Epigenome-wide DNA methylation was assessed using the Illumina EPIC array in 426 placentas from a sample of infants born < 28 weeks of gestation from the Extremely Low Gestational Age Newborn cohort. Associations between SES adversity and DNA methylation were assessed with robust linear regressions adjusted for covariates and controlled the false discovery rate at < 10%. We also examined whether such associations were sex specific. Indicators of SES adversity were associated with differential methylation at 33 CpG sites. Of the 33 identified CpG sites, 19 (57.6%) displayed increased methylation, and 14 (42.4%) displayed decreased methylation in association with at least one of the SES adversity factors. Sex differences were observed in DNA methylation associated with summative SES score; in which placentas derived from female pregnancies showed more robust differential CpG methylation than placentas from male pregnancies. Maternal SES adversity was associated with differential methylation of genes with key role in gene transcription and placental function, potentially altering immunity and stress response. Further investigation is needed to evaluate the role of epigenetic differences in mediating the association between maternal socioeconomic status during pregnancy and later life health outcomes in children.
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http://dx.doi.org/10.1080/15592294.2019.1614743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615526PMC
August 2019

Inorganic Arsenic as an Endocrine Disruptor: Modulation of the Glucocorticoid Receptor Pathway in Placental Cells via CpG Methylation.

Chem Res Toxicol 2019 03 4;32(3):493-499. Epub 2019 Mar 4.

Department of Environmental Sciences and Engineering, Gillings School of Global Public Health , University of North Carolina , Chapel Hill , North Carolina 27516 , United States.

Prenatal exposure to inorganic arsenic (iAs) has been associated with adverse developmental and reproductive outcomes. These outcomes may be tied to altered functionality of nuclear transcription factors such as the glucocorticoid receptor (GR) in the placenta and associated gene expression. The GR pathway is integral for proper fetal and placental development, and perturbations in this pathway may underlie observed associations between prenatal iAs exposure and adverse birth outcomes. We therefore set out to investigate whether iAs modulates the GR signaling pathway in placental cells. JEG-3 trophoblasts were exposed to environmentally-relevant doses of iAs, and mRNA expression assessed. To examine the links between iAs exposure, the GR signaling pathway, and epigenetic modification, DNA methylation levels were also quantified. Treatment with iAs altered the expression of 12 GR-genes that play a role in fetal and placental development. Furthermore, at a gene-specific level, mRNA abundance was associated with changes in DNA methylation patterning in JEG-3 cells, suggesting that the effects of iAs are mediated by epigenetic mechanisms. The identified target genes have been associated with prenatal iAs exposure, placental physiology, and fetal development. This study provides further evidence for iAs as an endocrine disruptor and provides insight as to the mechanisms by which prenatal iAs exposure may induce adverse birth outcomes.
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http://dx.doi.org/10.1021/acs.chemrestox.8b00352DOI Listing
March 2019

Wood Smoke Exposure Alters Human Inflammatory Responses to Viral Infection in a Sex-Specific Manner. A Randomized, Placebo-controlled Study.

Am J Respir Crit Care Med 2019 04;199(8):996-1007

1 Curriculum in Toxicology & Environmental Medicine.

Rationale: Exposure to particulates from burning biomass is an increasing global health issue. Burning biomass, including wood smoke, is associated with increased lower respiratory infections.

Objectives: To determine whether acute exposure to wood smoke modifies nasal inflammatory responses to influenza.

Methods: Healthy young adults (n = 39) were randomized to a 2-hour controlled chamber exposure to wood smoke, where exposure levels were controlled to particulate number (wood smoke particles [WSP]; 500 μg/cm) or filtered air, followed by nasal inoculation with a vaccine dose of live attenuated influenza virus (LAIV). Nasal lavage was performed before exposure (Day 0) and on Days 1 and 2 after exposure. Nasal lavage fluid cells were analyzed for inflammatory gene expression profiles, and cell-free fluid was assayed for cytokines.

Measurements And Main Results: Only IP-10 protein levels were affected, suppressed, by WSP exposure in aggregate analysis. Subsequent analysis indicated an exposure × sex interaction, prompting additional analyses of WSP- and LAIV-induced changes in males and females. Inflammation-related gene expression profiles differed between the sexes, at baseline (males greater than females), after LAIV inoculation (females greater than males), and after WSP exposure (increase in males and decrease in females), demonstrating that WSP- and LAIV-induced changes in antiviral defense responses in the nasal mucosa occur in a sex-specific manner.

Conclusions: WSP exposure resulted in minimal modification of LAIV-induced responses in aggregate analysis. In contrast, analyzing WSP-induced modification of LAIV responses in the sexes separately unmasked sex-specific differences in response to exposure. These data highlight the need for additional studies to understand sex-specific pollutant-induced effects. Clinical trial registered with www.clinicaltrials.gov (NCT02183753).
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http://dx.doi.org/10.1164/rccm.201807-1287OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467301PMC
April 2019

Discrimination exposure and DNA methylation of stress-related genes in Latina mothers.

Psychoneuroendocrinology 2018 12 16;98:131-138. Epub 2018 Aug 16.

School of Healthcare Science, Manchester Metropolitan University, Manchester, United Kingdom.

Latina mothers, who have the highest fertility rate among all ethnic groups in the US, are often exposed to discrimination. The epigenetic changes related to this discrimination are largely unknown. This study is the first to explore the relationship between discrimination and DNA methylation of stress regulatory genes in Latinas. Our sample was Latina women (n = 147) with a mean age of 27.6 years who were assessed at 24-32 weeks' gestation (T1) and 4-6 weeks postpartum (T2) and reside in the U.S. Blood was collected at T1, and the Everyday Discrimination Scale (EDS) was administered at T1 and T2. DNA Methylation at candidate gene regions was determined by bisulphite pyrosequencing. Associations between EDS and DNA methylation were assessed via zero-inflated Poisson models, adjusting for covariates and multiple-test comparisons. Discrimination was negatively associated with methylation at CpG sites within the glucocorticoid receptor (NR3C1) and brain-derived neurotrophic factor (BDNF) genes that were consistent over time. In addition, discrimination was negatively associated with methylation of a CpG in the glucocorticoid binding protein (FKBP5) at T1 but not at T2. This study underscores associations between discrimination and epigenetic markers of DNA methylation in Latinas that warrant further investigation to better understand the biological pathways and psychopathological effects of discrimination on Latina mothers and their families.
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http://dx.doi.org/10.1016/j.psyneuen.2018.08.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204298PMC
December 2018

Placental CpG methylation of infants born extremely preterm predicts cognitive impairment later in life.

PLoS One 2018 7;13(3):e0193271. Epub 2018 Mar 7.

Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.

Background: The placenta is the central regulator of maternal and fetal interactions. Perturbations of placental structure and function have been associated with adverse neurodevelopmental outcomes later in life. Placental CpG methylation represents an epigenetic modification with the potential to impact placental function, fetal development and child health later in life.

Study Design: Genome-wide placental CpG methylation levels were compared between spontaneous versus indicated deliveries from extremely preterm births (EPTBs) (n = 84). The association between the identified differentially methylated CpG sites and neurocognitive outcome at ten years of age was then evaluated.

Results: Spontaneous EPTB was associated with differential CpG methylation levels in 250 CpG sites (217 unique genes) with the majority displaying hypermethylation. The identified genes are known to play a role in neurodevelopment and are enriched for basic helix-loop-helix transcription factor binding sites. The placental CpG methylation levels for 17 of these sites predicted cognitive function at ten years of age.

Conclusion: A hypermethylation signature is present in DNA from placentas in infants with spontaneous EPTB. CpG methylation levels of critical neurodevelopment genes in the placenta predicted later life cognitive function, supporting the developmental origins of health and disease hypothesis (DOHaD).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193271PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841757PMC
June 2018

Distinguishing Human Peripheral Blood NK Cells from CD56CD16CD69CD103 Resident Nasal Mucosal Lavage Fluid Cells.

Sci Rep 2018 02 21;8(1):3394. Epub 2018 Feb 21.

Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Natural killer (NK) cells are members of the innate lymphoid cells group 1 (ILC1s), which play a critical role in innate host defense against viruses and malignancies. While many studies have examined the role of circulating peripheral blood (PB) CD56 NK cells, little is known about the resident CD56 cell population. Therefore, matched CD56 cells from nasal lavage fluid (NLF) and PB of smokers and non-smokers were compared phenotypically, via flow cytometry, and functionally, via NK-cell specific gene expression. NLF and PB CD56 cells had similar expression of CD56, but differentially expressed tissue residency (CD69 and CD103) and cytotoxicity (CD16) markers. In addition, NLF CD56 cells expressed lower levels of cytotoxicity-associated genes, perforin (PRF1) and granzyme B (GZMB), and increased levels of cytokines and cell signaling molecules, TRAIL, IFNGR2, and IL8, as compared to PB CD56 cells. In smokers, ITGA2 was downregulated in NLF CD56 cells, while markers of cytotoxic function were primarily downregulated in PB CD56 NK cells. Overall, NLF CD56 cells are a unique cell population that likely play a role in orchestrating innate immune responses in the nasal cavity, which is distinct from their role as a non-antigen-restricted cytotoxic CD56 lymphocytes in the PB.
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http://dx.doi.org/10.1038/s41598-018-21443-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821812PMC
February 2018

Environmental Influences on the Epigenome: Exposure- Associated DNA Methylation in Human Populations.

Annu Rev Public Health 2018 04 12;39:309-333. Epub 2018 Jan 12.

Department of Environmental Sciences and Engineering, and Curriculum in Toxicology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA; email: ,

DNA methylation is the most well studied of the epigenetic regulators in relation to environmental exposures. To date, numerous studies have detailed the manner by which DNA methylation is influenced by the environment, resulting in altered global and gene-specific DNA methylation. These studies have focused on prenatal, early-life, and adult exposure scenarios. The present review summarizes currently available literature that demonstrates a relationship between DNA methylation and environmental exposures. It includes studies on aflatoxin B, air pollution, arsenic, bisphenol A, cadmium, chromium, lead, mercury, polycyclic aromatic hydrocarbons, persistent organic pollutants, tobacco smoke, and nutritional factors. It also addresses gaps in the literature and future directions for research. These gaps include studies of mixtures, sexual dimorphisms with respect to environmentally associated methylation changes, tissue specificity, and temporal stability of the methylation marks.
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http://dx.doi.org/10.1146/annurev-publhealth-040617-014629DOI Listing
April 2018

Epigenetic Regulation of the Nitric Oxide Pathway, 17-α Hydroxyprogesterone Caproate, and Recurrent Preterm Birth.

Am J Perinatol 2018 07 14;35(8):721-728. Epub 2017 Dec 14.

Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Objective: We sought to evaluate nitric oxide pathway placental gene expression and the epigenome (CpG methylation) among women receiving 17-α hydroxyprogesterone caproate (17-OHPC) with and without recurrent preterm birth (PTB).

Study Design: This was a case-control study. We prospectively recruited women with ≥ 1 prior singleton spontaneous PTB <34 weeks receiving 17-OHPC. DNA and RNA were isolated from placentas. RNA abundance (gene expression) and the methylome were analyzed for 84 genes in nitric oxide pathways. Women with recurrent PTB <34 weeks (cases) were compared with those delivering at term (controls). Statistical analysis included multivariable models with Bonferroni's corrected -values.

Results: In this study, 17 women met inclusion criteria; 7 preterm cases (delivered at 22.6 ± 2.9 weeks) and 10 term controls (delivered at 38.5 ± 0.8 weeks). Groups had similar PTB history, race/ethnicity, and socioeconomic risk factors for PTB. Twenty-seven nitric oxide genes displayed differential expression ( < 0.05 and  < 0.10) when comparing placentas from preterm cases and term controls; all were downregulated in preterm cases. Eight hundred sixty corresponding CpG sites were differentially methylated between the preterm cases and term controls (Bonferroni's -value <0.05).

Conclusion: CpG methylation and gene expression patterns in nitric oxide pathway genes differ among placentas from recurrent PTB compared with term birth following 17-OHPC exposure.
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http://dx.doi.org/10.1055/s-0037-1613682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002888PMC
July 2018

Microorganisms in the human placenta are associated with altered CpG methylation of immune and inflammation-related genes.

PLoS One 2017 14;12(12):e0188664. Epub 2017 Dec 14.

Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.

Microorganisms in the placenta have been linked to adverse pregnancy outcomes as well as neonatal illness. Inflammation in the placenta has been identified as a contributing factor in this association, but the underlying biological mechanisms are not yet fully understood. The placental epigenome may serve as an intermediate between placental microbes and inflammation, contributing to adverse outcomes in the offspring. In the present study, genome-wide DNA methylation (n = 486,428 CpG sites) of 84 placentas was analyzed in relation to 16 species of placental microorganisms using samples collected from the Extremely Low Gestation Age Newborns (ELGAN) cohort. A total of n = 1,789 CpG sites, corresponding to n = 1,079 genes, displayed differential methylation (q<0.1) in relation to microorganisms. The altered genes encode for proteins that are involved in immune/inflammatory responses, specifically the NF-κB signaling pathway. These data support bacteria-dependent epigenetic patterning in the placenta and provide potential insight into mechanisms that associate the presence of microorganisms in the placenta to pregnancy and neonatal outcomes. This study lays the foundation for investigations of the placental microbiome and its role in placental function.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188664PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730116PMC
January 2018

Toxic metals in amniotic fluid and altered gene expression in cell-free fetal RNA.

Prenat Diagn 2017 12;37(13):1364-1366

Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27599, USA.

Both exposures to toxic metals, as well as deficiencies in essential metals, during pregnancy has been linked to a variety of negative reproductive outcomes. The exact etiologies of such outcomes and the effects of fetal exposure to these metals are largely unknown. Therefore, the ability to assess levels of these elements is critical to determining the underlying causes of such conditions and the effects that both essential and nonessential metals have on fetal development. Thus, using cell-free fetal RNA from amniotic fluid, we set out to measure the association between amniotic fluid levels of toxic and essential metals and fetal gene expression. We find that arsenic was associated with increased expression of 3 genes known to play roles in both birth-related and reproductive effects. The results highlight the potential for detrimental health effects of prenatal metals exposure and the potential to identify biomarkers of environmental exposure during this critical developmental period.
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http://dx.doi.org/10.1002/pd.5183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766286PMC
December 2017

Further Evidence of How Unbuffered Starvation at 4°C Influences Listeria monocytogenes EGD-e, HCC23, F2365, and Scott A.

J Food Prot 2017 10;80(10):1749-1759

1 Department of Food Science and Center for Food Safety and.

The soilborne pathogen Listeria monocytogenes frequently contaminates food products and food processing environments and is able to survive desiccation, high osmotic pressures, and starvation. However, little is known about how this pathogen survives starvation at 4°C. This study provides evidence that L. monocytogenes is able to survive total nutrient starvation for 4 weeks. L. monocytogenes strains EGD-e, Scott A, F2365, and HCC23 were starved individually in sterile water. Colony counts declined over 4 weeks, with Scott A declining the most rapidly. Transmission electron microscopy images revealed degradation of starving cell membranes and altered cytosols. Starving cells were subjected to the metabolic inhibitors fluoride, arsenite, 2,4-dinitrophenol, iodoacetate, and cyanide individually. Iodoacetate, which inhibits glyceraldehyde-3-phosphate dehydrogenase, completely reduced cultivable counts below the level of detection compared with the control starving cells; 2,4-dinitrophenol, which dissipates proton motive force, almost completely reduced cultivable counts. These results suggest that L. monocytogenes strains EGD-e, Scott A, F2365, and HCC23 are actively using part of the glycolysis pathway while starving. These results suggest that starving L. monocytogenes cells retain aspects of active metabolism.
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http://dx.doi.org/10.4315/0362-028X.JFP-17-041DOI Listing
October 2017

Genetic and epigenetic mechanisms underlying arsenic-associated diabetes mellitus: a perspective of the current evidence.

Epigenomics 2017 05 4;9(5):701-710. Epub 2017 May 4.

Department of Environmental Sciences & Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.

Chronic exposure to arsenic has been associated with the development of diabetes mellitus (DM), a disease characterized by hyperglycemia resulting from dysregulation of glucose homeostasis. This review summarizes four major mechanisms by which arsenic induces diabetes, namely inhibition of insulin-dependent glucose uptake, pancreatic β-cell damage, pancreatic β-cell dysfunction and stimulation of liver gluconeogenesis that are supported by both in vivo and in vitro studies. Additionally, the role of polymorphic variants associated with arsenic toxicity and disease susceptibility, as well as epigenetic modifications associated with arsenic exposure, are considered in the context of arsenic-associated DM. Taken together, in vitro, in vivo and human genetic/epigenetic studies support that arsenic has the potential to induce DM phenotypes and impair key pathways involved in the regulation of glucose homeostasis.
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http://dx.doi.org/10.2217/epi-2016-0097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480787PMC
May 2017

Chronic early childhood exposure to arsenic is associated with a TNF-mediated proteomic signaling response.

Environ Toxicol Pharmacol 2017 Jun 8;52:183-187. Epub 2017 Apr 8.

Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, United States. Electronic address:

Exposure to inorganic arsenic (iAs) in drinking water is a global public health concern and is associated with a range of health outcomes, including immune dysfunction. Children are a particularly sensitive population to the effects of inorganic arsenic, yet the biological mechanisms underlying adverse health outcomes are understudied. Here we used a proteomic approach to examine the effects of iAs exposure on circulating serum protein levels in a cross-sectional children's cohort in Mexico. To identify iAs-associated proteins, levels of total urinary arsenic (U-tAs) and its metabolites were determined and serum proteins assessed for differences in expression. The results indicate an enrichment of Tumor Necrosis Factor-(TNF)-regulated immune and inflammatory response proteins that displayed decreased expression levels in relation to increasing U-tAs. Notably, when analyzed in the context of the proportions of urinary arsenic metabolites in children, the most robust response was observed in relation to the monomethylated arsenicals. This study is among the first serum proteomics assessment in children exposed to iAs.
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http://dx.doi.org/10.1016/j.etap.2017.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796657PMC
June 2017

Effects of smoking and marination on the sensory characteristics of cold-cut chicken breast filets: A pilot study.

Food Sci Biotechnol 2016 31;25(6):1619-1625. Epub 2016 Dec 31.

1Department of Food Science, University of Arkansas, Fayetteville, AR 72704 USA.

This study aimed to determine individual and combined effects of smoking and marination on the sensory characteristics of boneless, skinless chicken breast meat. Four types of cooked, cold-cut chicken breast meat, i.e., marinated cooked, marinated smoked, and controls of non-marinated cooked and non-marinated smoked chicken, were evaluated for 28 sensory characteristics. Marination significantly increased saltiness, sweetness, roasted flavor, smoked flavor, and moistness of the cold-cut chicken breast meat. In addition, smoking significantly enhanced the saltiness, bitterness, roasted flavor, smoked flavor, and moistness of mass. Interestingly, a combination of smoking and marination processes resulted in a synergistic increase in the perceived moistness of mass compared to their individual treatments. In conclusion, this study demonstrates individual and combined influences of smoking and marination on the sensory characteristics of cold-cut chicken breast meat.
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http://dx.doi.org/10.1007/s10068-016-0249-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6049239PMC
December 2016

E-cigarette use results in suppression of immune and inflammatory-response genes in nasal epithelial cells similar to cigarette smoke.

Am J Physiol Lung Cell Mol Physiol 2016 07 10;311(1):L135-44. Epub 2016 Jun 10.

Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina; Center for Environmental Medicine, Asthma, and Lung Biology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina; and Division of Clinical Pharmacology, Departments of Medicine and Bioengineering & Therapeutic Sciences, University of California San Francisco, San Francisco, California

Exposure to cigarette smoke is known to result in impaired host defense responses and immune suppressive effects. However, the effects of new and emerging tobacco products, such as e-cigarettes, on the immune status of the respiratory epithelium are largely unknown. We conducted a clinical study collecting superficial nasal scrape biopsies, nasal lavage, urine, and serum from nonsmokers, cigarette smokers, and e-cigarette users and assessed them for changes in immune gene expression profiles. Smoking status was determined based on a smoking history and a 3- to 4-wk smoking diary and confirmed using serum cotinine and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels. Total RNA from nasal scrape biopsies was analyzed using the nCounter Human Immunology v2 Expression panel. Smoking cigarettes or vaping e-cigarettes resulted in decreased expression of immune-related genes. All genes with decreased expression in cigarette smokers (n = 53) were also decreased in e-cigarette smokers. Additionally, vaping e-cigarettes was associated with suppression of a large number of unique genes (n = 305). Furthermore, the e-cigarette users showed a greater suppression of genes common with those changed in cigarette smokers. This was particularly apparent for suppressed expression of transcription factors, such as EGR1, which was functionally associated with decreased expression of 5 target genes in cigarette smokers and 18 target genes in e-cigarette users. Taken together, these data indicate that vaping e-cigarettes is associated with decreased expression of a large number of immune-related genes, which are consistent with immune suppression at the level of the nasal mucosa.
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http://dx.doi.org/10.1152/ajplung.00170.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967187PMC
July 2016

A cross-study analysis of prenatal exposures to environmental contaminants and the epigenome: support for stress-responsive transcription factor occupancy as a mediator of gene-specific CpG methylation patterning.

Environ Epigenet 2016 Jan 30;2(1). Epub 2016 Jan 30.

Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.

A biological mechanism by which exposure to environmental contaminants results in gene-specific CpG methylation patterning is currently unknown. We hypothesize that gene-specific CpG methylation is related to environmentally perturbed transcription factor occupancy. To test this hypothesis, a database of 396 genes with altered CpG methylation either in cord blood leukocytes or placental tissue was compiled from 14 studies representing assessments of six environmental contaminants. Subsequently, an approach was used to identify transcription factor binding sites enriched among the genes with altered CpG methylation in relationship to the suite of environmental contaminants. For each study, the sequences of the promoter regions (representing -1000 to +500 bp from the transcription start site) of all genes with altered CpG methylation were analyzed for enrichment of transcription factor binding sites. Binding sites for a total of 56 unique transcription factors were identified to be enriched within the promoter regions of the genes. Binding sites for the Kidney-Enriched Krupple-like Factor 15, a known responder to endogenous stress, were enriched ( < 0.001-0.041) among the genes with altered CpG methylation associated for five of the six environmental contaminants. These data support the transcription factor occupancy theory as a potential mechanism underlying environmentally-induced gene-specific CpG methylation.
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http://dx.doi.org/10.1093/eep/dvv011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824001PMC
January 2016

Apgar Score at 5 Minutes Is Associated with Mortality in Extremely Preterm Infants Even after Transfer to an All Referral NICU.

Am J Perinatol 2015 Nov 9;32(13):1268-72. Epub 2015 Jun 9.

Division of Neonatology, Department of Pediatrics, The Ohio State University, Columbus, Ohio.

Objective: The Apgar score has been shown to have utility in predicting mortality in the extremely preterm infant in delivery hospital populations, where most mortality occurs within 12 hours of birth. We tested the hypothesis that the 5 minute Apgar score would remain associated with mortality in extremely preterm infants after transfer from the delivery hospital to an all referral neonatal intensive care unit at an average age of 10 days.

Study Design: A retrospective analysis of 454 infants born at < 27 weeks gestation.

Results: The median Apgar score was 3 at 1 minute (interquartile range [IQR] 2-6) and 6 at 5 minutes (IQR 4-7). The Apgar score increased from 1 to 5 minutes by 2.0 ± 1.7 (p < 0.001). In logistic regression modeling, an Apgar score of < 5 at 5 minutes was associated with an increased mortality (odds ratio 1.76 [95% confidence interval 1.06-2.94], p < 0.05), but not morbidities.

Conclusion: Infants born at < 27 weeks gestation admitted to an all referral children's hospital at a mean age of 10 days with a 5 minute Apgar < 5 are at an increased risk of mortality. Our findings continue to support the importance of the Apgar score given at delivery even in the extremely preterm infant referred to a nondelivery children's hospital.
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http://dx.doi.org/10.1055/s-0035-1554803DOI Listing
November 2015

Sensory impact of chemical and natural antimicrobials on poultry products: a review.

Poult Sci 2015 Jul 25;94(7):1699-710. Epub 2015 May 25.

Department of Food Science, University of Arkansas, 2650 North Young Avenue, Fayetteville, AR 72704, U.S.A

Antimicrobial agents are added to poultry products after slaughter to prevent the growth of pathogenic and spoilage microorganisms and to extend the shelf-life of these products. Antimicrobials can be either natural or chemical, which may affect the sensory attributes at elevated concentrations, such as surface color, odor, flavor, taste, and texture of the poultry products. Thus, when selecting antimicrobials for use in poultry processing, it is vital to consider the antimicrobial-induced changes in sensory aspects from the consumers' perspectives. In spite of its importance, there has been no systematic review on the influences of antimicrobials on sensory aspects of poultry products. This paper reviews the major antimicrobial agents used in the poultry processing industry and their effects on sensory aspects of the poultry products.
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http://dx.doi.org/10.3382/ps/pev134DOI Listing
July 2015

Sweetgum: An ancient source of beneficial compounds with modern benefits.

Pharmacogn Rev 2015 Jan-Jun;9(17):1-11

Sea Star International LLC, Fayetteville, Arkansas, USA ; Department of Food Science and Center for Food Safety, University of Arkansas, Fayetteville, Arkansas, USA.

Sweetgum trees are large, deciduous trees found in Asia and North America. Sweetgum trees are important resources for medicinal and other beneficial compounds. Many of the medicinal properties of sweetgum are derived from the resinous sap that exudes when the outer bark of the tree has been damaged. The sap, known as storax, has been used for centuries to treat common ailments such as skin problems, coughs, and ulcers. More recently, storax has proven to be a strong antimicrobial agent even against multidrug resistant bacteria such as methicillin-resistant Staphylococcus aureus. In addition to the sap, the leaves, bark, and seeds of sweetgum also possess beneficial compounds such as shikimic acid, a precursor to the production of oseltamivir phosphate, the active ingredient in Tamiflu®-an antiviral drug effective against several influenza viruses. Other extracts derived from sweetgum trees have shown potential as antioxidants, anti-inflammatory agents, and chemopreventive agents. The compounds found in the extracts derived from sweetgum sap suppress hypertension in mice. Extracts from sweetgum seeds have anticonvulsant effects, which may make them suitable in the treatment of epilepsy. In addition to the potential medicinal uses of sweetgum extracts, the extracts of the sap possess antifungal activity against various phytopathogenic fungi and have been effective treatments for reducing nematodes and the yellow mosquito, Aedes aegypti, populations thus highlighting the potential of these extracts as environment-friendly pesticides and antifungal agents. The list of value-added products derived from sweetgum trees can be increased by continued research of this abundantly occurring tree.
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http://dx.doi.org/10.4103/0973-7847.156307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441155PMC
May 2015

CCK1-receptor stimulation protects against gut mediator-induced lung damage during endotoxemia.

Cell Physiol Biochem 2013 20;32(6):1878-90. Epub 2013 Dec 20.

Department of General, Visceral and Transplant Surgery, University Hospital of Tuebingen, Tuebingen, Germany.

Background/aims: Cholecystokinin 1-receptor (CCK1-R) activation by long chain fatty acid (LCFA) absorption stimulates vago-vagal reflex pathways in the brain stem. The present study determines whether this reflex also activates the cholinergic anti-inflammatory pathway, a pathway known to modulate cytokine release during endotoxemia.

Methods: Mesenteric lymph was obtained from wild type (WT) and CCK1-R knockout (CCK1-R(-/-)) mice intraperitoneally challenged with Lipopolysaccharid (LPS) (endotoxemic lymph, EL) and intestinally infused with vehicle or LCFA-enriched solution. The lymph was analyzed for TNFα, IL-6 and IL-10 concentration and administered to healthy recipient mice via jugular infusion. Alveolar wall thickness, myeloperoxidase (MPO) and TUNEL positive cells were determined in lung tissue of recipient mice.

Results: LCFA infusion in WT mice reduced TNFα concentration in EL by 49% compared to vehicle infusion, but had no effect in CCK1-R(-/-) mice. EL significantly increased the alveolar wall thickness, the number of MPO-positive and TUNEL-positive cells compared to control lymph administration. LCFA infusion in WT, but not in CCK1R(-/-) mice, significantly reduced these pathological effects of EL.

Conclusion: During endotoxemia enteral LCFA absorption reduces TNFα release into mesenteric lymph and attenuates histomorphologic parameters of lung dysfunction. Failure to elicit this effect in CCK1R(-/-) mice demonstrates that anti-inflammatory properties of LCFAs are mediated through CCK1-Rs.
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http://dx.doi.org/10.1159/000356644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959982PMC
August 2014

Quantitative risk analysis for potentially resistant E. coli in surface waters caused by antibiotic use in agricultural systems.

J Environ Sci Health B 2014 ;49(2):124-33

a Department of Cell Biology, Microbiology and Molecular Biology , University of South Florida , Tampa , Florida , USA.

Antibiotics are frequently used in agricultural systems to promote livestock health and to control bacterial contaminants. Given the upsurge of the resistant fecal indicator bacteria (FIB) in the surface waters, a novel statistical method namely, microbial risk assessment (MRA) was performed, to evaluate the probability of infection by resistant FIB on populations exposed to recreational waters. Diarrheagenic Escherichia coli, except E. coli O157:H7, were selected for their prevalence in aquatic ecosystem. A comparative study between a typical E. coli pathway and a case scenario aggravated by antibiotic use has been performed via Crystal Ball® software in an effort to analyze a set of available inputs provided by the US institutions including E. coli concentrations in US Great Lakes through using random sampling and probability distributions. Results from forecasting a possible worst-case scenario dose-response, accounted for an approximate 50% chance for 20% of the exposed human populations to be infected by recreational water in the U.S. However, in a typical scenario, there is a 50% chance of infection for only 1% of the exposed human populations. The uncertain variable, E. coli concentration accounted for approximately 92.1% in a typical scenario as the major contributing factor of the dose-response model. Resistant FIB in recreational waters that are exacerbated by a low dose of antibiotic pollutants would increase the adverse health effects in exposed human populations by 10 fold.
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http://dx.doi.org/10.1080/03601234.2014.847220DOI Listing
July 2014

Electrostatic spraying of food-grade organic and inorganic acids and plant extracts to decontaminate Escherichia coli O157:H7 on spinach and iceberg lettuce.

J Food Sci 2012 Jul;77(7):M391-6

Dept of Food Science, Univ of Arkansas, Fayetteville, AR 72704, USA.

Unlabelled: The prevalence of foodborne illnesses is continually on rise. In the U.S.A., Escherichia coli O157:H7 (E. coli) has been associated with several outbreaks in minimally processed foods. Spinach and lettuce pose higher food safety risks and recurring food recalls suggest the insufficiency of current disinfection strategies. We aimed at offering a natural antimicrobial alternative using organic acids (malic, tartaric, and lactic acids [MA, TA, and LA, respectively]) and grape seed extract (GSE) and a novel application method using electrostatic spraying to evenly distribute the antimicrobials onto produce. Spinach and lettuce samples were washed, sanitized with sodium hypochlorite solution (6.25 mL/L), dip inoculated in water containing E. coli (7.0 log CFU/mL) for 24 h, and rewashed with sterile water to remove nonadhered pathogens. The samples were sprayed electrostatically with MA, LA, and GSE alone and in combinations and for comparison, with phosphoric acid (PA) and pH controls with deionized water adjusted to 1.5/2.3/3.6 and stored at 4 °C. When combined with LA (3%), MA (3%) showed 2.1 to 4.0 log CFU/g reduction of E. coli between the days 1 and 14 on spinach and 1.1 to 2.5 log CFU/g reduction on lettuce. Treatment with PA (1.5%) and PA (1.5%)-GSE (2%) exhibited 1.1 to 2.1 log CFU/g inhibition of E. coli on spinach during the 14-d storage. Our findings demonstrated the efficacy of electrostatic spraying of MA, LA, and GSE on fresh produce to improve the safety and lower the public health burden linked to produce contamination.

Practical Application: Electrostatic spraying is an emerging technique that can be adopted to improve the distribution and application of antimicrobials during fresh produce sanitation. Relatively simple and quick, the process can access most/all parts of produce surface and offer protection from food pathogens. The use of malic and lactic acids with or without grape seed extract can serve as effective antimicrobials when sprayed electrostatically, lowering the risk from postcontamination issues with spinach and iceberg lettuce. This application technology can be extended to improve the commercial food safety of other produce, fruits, poultry, and meat.
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http://dx.doi.org/10.1111/j.1750-3841.2012.02719.xDOI Listing
July 2012

A TAT-frataxin fusion protein increases lifespan and cardiac function in a conditional Friedreich's ataxia mouse model.

Hum Mol Genet 2012 Mar 23;21(6):1230-47. Epub 2011 Nov 23.

Riley Heart Research Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Friedreich's ataxia (FRDA) is the most common inherited human ataxia and results from a deficiency of the mitochondrial protein, frataxin (FXN), which is encoded in the nucleus. This deficiency is associated with an iron-sulfur (Fe-S) cluster enzyme deficit leading to progressive ataxia and a frequently fatal cardiomyopathy. There is no cure. To determine whether exogenous replacement of the missing FXN protein in mitochondria would repair the defect, we used the transactivator of transcription (TAT) protein transduction domain to deliver human FXN protein to mitochondria in both cultured patient cells and a severe mouse model of FRDA. A TAT-FXN fusion protein bound iron in vitro, transduced into mitochondria of FRDA deficient fibroblasts and reduced caspase-3 activation in response to an exogenous iron-oxidant stress. Injection of TAT-FXN protein into mice with a conditional loss of FXN increased their growth velocity and mean lifespan by 53% increased their mean heart rate and cardiac output, increased activity of aconitase and reversed abnormal mitochondrial proliferation and ultrastructure in heart. These results show that a cell-penetrant peptide is capable of delivering a functional mitochondrial protein in vivo to rescue a very severe disease phenotype, and present the possibility of TAT-FXN as a protein replacement therapy.
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http://dx.doi.org/10.1093/hmg/ddr554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3284115PMC
March 2012

Electrostatic sprays of food-grade acids and plant extracts are more effective than conventional sprays in decontaminating Salmonella Typhimurium on spinach.

J Food Sci 2010 Nov-Dec;75(9):M574-9

Dept. of Food Science, Univ. of Arkansas, Fayetteville, AR 72704, USA.

About 40000 people fall victim to Salmonella infections every year in the United States. Recent occurrences of Salmonella contaminated spinach and its recalls have accelerated the need for efficient antimicrobials targeting these pathogens. Our study was aimed at evaluating the inhibitory properties of malic, tartaric, and lactic acids, and grape seed extract (GSE) alone and in combinations and their application methods against Salmonella Typhimurium-inoculated spinach using a response surface method. Fresh spinach leaves were washed, disinfected with sodium hypochlorite solution (0.04% v/v), rewashed with sterile deionized (DI) water, and inoculated with a 2nd-day culture of S. Typhimurium (7.0 log CFU/mL). Adhered S. Typhimurium population on day 0 were 7.5 log CFU/g. These were treated with individual and combinations of organic acids with GSE or DI water (control) adjusted to the same pH as that of the test solutions with both the modes of application and leaves were refrigerated at 4 °C. Malic acid (2%) in combination with GSE (3%) or lactic acid (3%) sprayed electrostatically showed reductions of 2.6 to 3.3 log CFU/g compared to lower log reductions (0.0 to 0.3 log CFU/g) by day 14 if sprayed conventionally. These findings indicate that malic acid in combination with GSE/lactic acid solutions applied by electrostatic spraying exhibited higher inhibition of pathogens than conventional spraying and can be used for commercial applications to enhance food safety.
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http://dx.doi.org/10.1111/j.1750-3841.2010.01859.xDOI Listing
September 2011
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