EOH Events

EOH Departmental Calendar

Event
Thu 11/14/2019 11:00AM - 12:00PM
EOH Journal Club
Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver EOH Journal Club
Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver
Thu 11/14/2019 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Jenna Kuhn

Paper: Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a Highthroughput Targeted Metabolomics Approach

Authors: Nanyang Yu, Si Wei, Meiying Li, Jingping Yang, Kan Li, Ling Jin, Yuwei Xie, John P. Giesy, Xiaowei Zhang & Hongxia Yu

Abstract:
Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine, and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects.


4140 Public Health, Young Seminar Room
Fri 11/15/2019 1:00PM - 2:00PM
EOH Seminar Series
Public access to environ health data in Pennsylvania: What are the gaps? What is readily available? EOH Seminar Series
Public access to environ health data in Pennsylvania: What are the gaps? What is readily available?
Fri 11/15/2019 1:00PM - 2:00PM
A719 Public Health


A719 Public Health
Thu 11/21/2019 11:00AM - 12:00PM
EOH Journal Club
Association of Environmental Toxins With Amyotrophic Lateral Sclerosis EOH Journal Club
Association of Environmental Toxins With Amyotrophic Lateral Sclerosis
Thu 11/21/2019 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Fan Wu

Paper: Association of Environmental Toxins With Amyotrophic Lateral Sclerosis

Authors: Feng-Chiao Su,PhD; Stephen A. Goutman,MD; Sergey Chernyak,PhD; Bhramar Mukherjee,PhD; Brian C. Callaghan,MD; Stuart Batterman,PhD; Eva L. Feldman,MD,PhD

Abstract:
IMPORTANCE
Persistent environmental pollutants may represent a modifiable risk factor involved in the gene-time-environment hypothesis in amyotrophic lateral sclerosis (ALS).

OBJECTIVE
To evaluate the association of occupational exposures and environmental toxins on the odds of developing ALS in Michigan.

DESIGN, SETTING, AND PARTICIPANTS
Case-control study conducted between 2011 and 2014
at a tertiary referral center for ALS. Cases were patients diagnosed as having definitive,
probable, probable with laboratory support, or possible ALS by revised El Escorial criteria;
controls were excluded if they were diagnosed as having ALS or another neurodegenerative
condition or if they had a family history of ALS in a first- or second-degree blood relative.
Participants completed a survey assessing occupational and residential exposures. Blood
concentrations of 122 persistent environmental pollutants, including organochlorine
pesticides (OCPs), polychlorinated biphenyls (PCBs), and brominated flame retardants
(BFRs), were measured using gas chromatography–mass spectrometry. Multivariable models
with self-reported occupational exposures in various exposure time windows and
environmental toxin blood concentrations were separately fit by logistic regression models.
Concordance between the survey data and pollutant measurements was assessed using the
nonparametric Kendall τ correlation coefficient.

MAIN OUTCOMES AND MEASURES
Occupational and residential exposures to environmental toxins, and blood concentrations of 122 persistent environmental pollutants, including OCPs,
PCBs, and BFRs.

RESULTS
Participants included 156 cases (mean [SD] age, 60.5 [11.1] years; 61.5%male) and 128 controls (mean [SD] age, 60.4 [9.4] years; 57.8%male); among them, 101 cases and 110 controls had complete demographic and pollutant data. Survey data revealed that reported
pesticide exposure in the cumulative exposure windows was significantly associated with ALS
(odds ratio [OR] = 5.09; 95%CI, 1.85-13.99; P = .002). Military service was also associated
with ALS in 2 time windows (exposure ever happened in entire occupational history:
OR = 2.31; 95%CI, 1.02-5.25; P = .046; exposure ever happened 10-30 years ago: OR = 2.18;
95%CI, 1.01-4.73; P = .049). A multivariable model of measured persistent environmental
pollutants in the blood, representing cumulative occupational and residential exposure,
showed increased odds of ALS for 2 OCPs (pentachlorobenzene: OR = 2.57; 95%CI, 1.31-5.02;
P = .006; and cis-chlordane: OR = 6.51; 95%CI, 2.05-20.73; P = .002) and 1 PCB (PCB 151:
OR = 1.66; 95%CI, 1.03-2.67; P = .04. There was modest concordance between survey data
and the measurements of persistent environmental pollutants in blood; significant Kendall τ
correlation coefficients ranged from −0.18 (Dacthal and “use pesticides to treat home or
yard”) to 0.24 (trans-nonachlor and “store lawn care products in garage”).

CONCLUSIONS AND RELEVANCE
In this study, persistent environmental pollutants measured in blood were significantly associated with ALS and may represent modifiable ALS disease risk
factors.


4140 Public Health, Young Seminar Room
Thu 12/5/2019 11:00AM - 12:00PM
EOH Journal Club
Protein Arginine Methyltransferase 4 (PRMT4) mediates lymphopenia in experimental sepsis EOH Journal Club
Protein Arginine Methyltransferase 4 (PRMT4) mediates lymphopenia in experimental sepsis
Thu 12/5/2019 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Rushikesh Deshpande

Paper: Protein Arginine Methyltransferase 4 (PRMT4) mediates lymphopenia in experimental sepsis

Authors: Yandong Lai, Xiuying Li, Tiao Li, Yan Chen, Chen Long, Toru Nyunoya, Kong Chen,Georgios D. Kitsios,Seyed Mehdi Nouraie,Yingze Zhang, Bryan J. McVerry, Janet S. Lee,Rama K. Mallampalli, and Chunbin Zou

Abstract:
Onehallmark of sepsis is a reduced number of lymphocytes, termed lymphopenia,that occurs from decreased lymphocyte proliferation or increased cell death contributing to immune suppression. Histone modification enzymes regulate immunity by epigenetically modulating chromatin architecture, however, the role of these enzymes in lymphopenia remains elusive. In this study, we identified that a chromatin modulator Protein Arginine N-methyltransferase 4/Coactivator-Associated Arginine Methyltransferase 1 (PRMT4/ CARM1) that is elevated systemically inseptic patients and experimental sepsis, and is crucialfor inducing T-lymphocyte apoptosis.An E3 ubiquitin ligase SCFFBXO9 docks on PRMT4 via a phosphodegron to ubiquitinate the protein at K228 for ubiquitin proteasomal degradation.  High PRMT4 expression resulted from reduced levels of SCFFBXO9 that led to increased lymphocyte cell death after Escherichia coliorlipopolysaccharide(LPS) exposure. Ectopic expression of PRMT4 protein caused substantially mphocytedeathvia caspase 3 mediated cell death signaling, and knockout of PRMT4 abolished LPS mediated lymphocyte cell death. PRMT4 inhibition with a small molecule compound attenuated lymphocyte death in complementary models of sepsis. These findings demonstrate a previously uncharacterized role of a key chromatin modulator in lymphocytesurvival that may shed light on devising unique therapeutic modalities to lessen severity of septic immunosuppression.


4140 Public Health, Young Seminar Room

Recent Events

EOH Journal Club

EOH Journal Club - Spring 2017 - Heng Bai

Thursday 3/23 11:00AM - 12:00PM
EOH Journal Club Seminar - Spring 2017

Date: Thursday March 23, 2017
Time: 11am - 12pm
Presenter: Heng Bai

Paper: 
In vivo activation of a T helper 2-driven innate immune response in
lung fibrosis induced by multi-walled carbon nanotubes

Authors: Dong J, Ma Q

Abstract:
Pulmonary exposure to certain forms of carbon nanotubes (CNT) induces
fibrosing lesions in the lungs that manifest an acute inflammation
followed by chronic interstitial fibrosis. The mechanism of CNT-induced
fibrogenesis is largely unknown. The biphasic development with
drastically distinct pathologic manifestations suggests a junction of
acute-to-chronic transition. Here we analyzed the molecular pathways and
regulators underlying the pathologic development of CNT-induced lung
fibrosis. Mice were exposed to multi-walled CNT (MWCNT; XNRI MWNT-7,
Mitsui; 40 μg) by pharyngeal aspiration for 7 days along with vehicle
and carbonaceous controls. Genome-wide microarray analyses of the lungs
identified a range of differentially expressed genes that potentially
function in the acute-to-chronic transition through pathways involving
immune and inflammatory regulation, responses to stress and
extracellular stimuli, and cell migration and adhesion. In particular, a
T helper 2 (Th2)-driven innate immune response was significantly
enriched. We then demonstrated that MWCNT induced the expression of Th2
cytokines interleukin (IL)-4 and IL-13, and a panel of signature
downstream genes, such as Il4i1, Chia, and Ccl11/Eotaxin, time
dependently. Induction of Th2 cytokines took place in CD4+ T lymphocytes
indicating activation of Th2 cells. Furthermore, induction involved
activation of a Th2 cell-specific signaling pathway through
phosphorylation of STAT6 and up-regulation of GATA-3 to mediate the
transcription of Th2 target genes. Our study uncovers activation of a
Th2-driven immune/inflammatory response during pulmonary fibrosis
development induced by MWCNT. The findings provide novel insights into
the molecular events that control the transition from an acute
inflammatory response to chronic fibrosis through Th2 functions in
CNT-exposed lungs



Click Here For Article

Last Updated On Friday, February 24, 2017 by Orbell, Adam W
Created On Friday, February 24, 2017

OctNovember 2019Dec
SunMonTueWedThuFriSat
272829303112
3456789
10111213141516
17181920212223
24252627282930
1234567

Submit events and news

Enter upcoming calendar events or share your school news and announcements at publichealth.pitt.edu/submit.