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Article ; Online: An ultrasensitive microfluidic approach reveals correlations between the physico-chemical and biological activity of experimental peptide antibiotics

Jehangir Cama / Kareem Al Nahas / Marcus Fletcher / Katharine Hammond / Maxim G. Ryadnov / Ulrich F. Keyser / Stefano Pagliara

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 12

Abstract: Abstract Antimicrobial resistance challenges the ability of modern medicine to contain infections. Given the dire need for new antimicrobials, polypeptide antibiotics hold particular promise. These agents hit multiple targets in bacteria starting with ... ...

Abstract	Abstract Antimicrobial resistance challenges the ability of modern medicine to contain infections. Given the dire need for new antimicrobials, polypeptide antibiotics hold particular promise. These agents hit multiple targets in bacteria starting with their most exposed regions—their membranes. However, suitable approaches to quantify the efficacy of polypeptide antibiotics at the membrane and cellular level have been lacking. Here, we employ two complementary microfluidic platforms to probe the structure–activity relationships of two experimental series of polypeptide antibiotics. We reveal strong correlations between each peptide’s physicochemical activity at the membrane level and biological activity at the cellular level. We achieve this knowledge by assaying the membranolytic activities of the compounds on hundreds of individual giant lipid vesicles, and by quantifying phenotypic responses within clonal bacterial populations with single-cell resolution. Our strategy proved capable of detecting differential responses for peptides with single amino acid substitutions between them, and can accelerate the rational design and development of peptide antimicrobials.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Respirator use and its impact on particulate matter exposure in aluminum manufacturing facilities

Sa Liu / Elizabeth Noth / Ellen Eisen / Mark R Cullen / Katharine Hammond

Scandinavian Journal of Work, Environment & Health, Vol 44, Iss 5, Pp 547-

2018 Volume 554

Abstract: OBJECTIVES: As part of a large epidemiologic study of particulate health effect, this study aimed to report respirator use among total particulate matter (TPM) samples collected in a major aluminum manufacturing company from 1966‒2013 and evaluate the ... ...

Abstract	OBJECTIVES: As part of a large epidemiologic study of particulate health effect, this study aimed to report respirator use among total particulate matter (TPM) samples collected in a major aluminum manufacturing company from 1966‒2013 and evaluate the impact of respirator-use adjustment on exposure estimation. METHODS: Descriptive analyses were performed to evaluate respirator use across facilities and by facility type and job. Protection factors were applied to TPM measurements for recorded respirator use. Estimated TPM exposure for each job ‒ before and after respirator-use adjustment ‒ were compared to assess the impact of adjustment on exposure estimation. RESULTS: Respirator use was noted for 37% of 12 402 full-shift personal TPM samples. Measured TPM concentration ranged from less than detectable to 8220 mg/m3, with arithmetic mean, median and standard deviation being 10.6, 0.87 and 130 mg/m^3, respectively. Respirators were used more often in smelting facilities (52% of TPM measurements) than in fabricating (17%) or refinery facilities (28%) (P<0.01). Sixty-two percent of jobs in smelting facilities were subject to respirator-use adjustment, whereas it was 20% and 70% in fabricating and refinery facilities, respectively. Applying protection factors to TPM measurements significantly reduced estimated job mean TPM exposures and changed exposure categories in these facilities, with larger impact in smelting than fabricating facilities. CONCLUSIONS: Respirator use varied by time, facility and job. Adjusting respirator use resulted in differential impact in smelting and fabricating facilities, which will need to be incorporated into ongoing epidemiologic studies accordingly.
Keywords	respirator use ; particulate matter exposure ; aluminum manufacturing facility ; workplace protection factor ; fabrication ; assigned protection factor ; exposure ; particulate matter ; job exposure matrix ; aluminum ; smelter ; refinery ; Public aspects of medicine ; RA1-1270
Subject code	306
Language	English
Publishing date	2018-09-01T00:00:00Z
Publisher	Nordic Association of Occupational Safety and Health (NOROSH)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Air pollution exposure is linked with methylation of immunoregulatory genes, altered immune cell profiles, and increased blood pressure in children

Mary Prunicki / Nicholas Cauwenberghs / Justin Lee / Xiaoying Zhou / Hesam Movassagh / Elizabeth Noth / Fred Lurmann / S. Katharine Hammond / John R. Balmes / Manisha Desai / Joseph C. Wu / Kari C. Nadeau

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 12

Abstract: Abstract Ambient air pollution exposure is associated with cardiovascular dysregulation and immune system alterations, yet no study has investigated both simultaneously in children. Understanding the multifaceted impacts may provide early clues for ... ...

Abstract	Abstract Ambient air pollution exposure is associated with cardiovascular dysregulation and immune system alterations, yet no study has investigated both simultaneously in children. Understanding the multifaceted impacts may provide early clues for clinical intervention prior to actual disease presentation. We therefore determined the associations between exposure to multiple air pollutants and both immunological outcomes (methylation and protein expression of immune cell types associated with immune regulation) and cardiovascular outcomes (blood pressure) in a cohort of school-aged children (6–8 years; n = 221) living in a city with known elevated pollution levels. Exposure to fine particular matter (PM2.5), carbon monoxide (CO), and ozone (O3) was linked to altered methylation of most CpG sites for genes Foxp3, IL-4, IL-10 and IFN-g, all involved in immune regulation (e.g. higher PM2.5 exposure 1 month prior to the study visit was independently associated with methylation of the IL-4 CpG24 site (est = 0.16; P = 0.0095). Also, immune T helper cell types (Th1, Th2 and Th17) were associated with short-term exposure to PM2.5, O3 and CO (e.g. Th1 cells associated with PM2.5 at 30 days: est = − 0.34, P < 0.0001). Both B cells (est = − 0.19) and CD4+ cells (est = 0.16) were associated with 1 day NO2 exposure (P ≤ 0.031), whereas CD4+ and CD8+ cells were associated with chronic exposure to PAH456, NOx and/or NO2 (P ≤ 0.038 for all). Finally, diastolic BP (DBP) was inversely associated with long-term exposures to both CO and PAH456, and both systolic and pulse pressure were associated with short-term NO2 and chronic NOx exposure. Our findings demonstrate links between air pollution exposure and methylation of immunoregulatory genes, immune cell profiles and blood pressure, suggesting that even at a young age, the immune and cardiovascular systems are negatively impacted by exposure to air pollution.
Keywords	Medicine ; R ; Science ; Q
Subject code	333
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: An assessment of health risks and mortality from exposure to secondhand smoke in Chinese restaurants and bars.

Ruiling Liu / Yuan Jiang / Qiang Li / S Katharine Hammond

PLoS ONE, Vol 9, Iss 1, p e

2014 Volume 84811

Abstract: Introduction Smoking is generally not regulated in restaurants or bars in China, or the restrictions are not fully implemented if there are any, while the related hazard health effects are not recognized by the majority of the Chinese population. ... ...

Abstract	Introduction Smoking is generally not regulated in restaurants or bars in China, or the restrictions are not fully implemented if there are any, while the related hazard health effects are not recognized by the majority of the Chinese population. Objectives This study aims to assess the excess health risks and mortality attributed to secondhand smoke (SHS) exposure in restaurants and bars for both servers and patrons to provide necessary evidence for advancing tobacco control in this microenvironment. Methods Two approaches were used for the assessment. One is a continuous approach based on existing field measurements and Repace and Lowrey's dose-response model, and the other is a categorical approach based on exposure or not and epidemiological studies. Results Based on the continuous approach, servers were estimated to have a lifetime excess risk (LER) of lung cancer death (LCD) of 730 to 1,831×10(-6) for working five days a week for 45 years in smoking restaurants and 1,862 to 8,136×10(-6) in smoking bars, and patrons could have a LER of LCD of 47 to 117×10(-6) due to visiting smoking restaurants for an average of 13 minutes a day for 60 years, and 119 to 522×10(-6) due to visiting smoking bars. The categorical approach estimated that SHS exposure in restaurants and bars alone caused 84 LCD and 57 ischemic heart disease (IHD) deaths among nonsmoking servers and 1,2419 LCDs and 1,689 IHD deaths among the nonsmoking patron population. Conclusions SHS exposure in restaurants and bars alone can impose high lifetime excess risks of lung cancer death and ischemic heart disease deaths to both servers and patrons, and can cause a significant number of deaths each year in China. These health risks and deaths can be prevented by banning smoking in restaurants and bars and effectively implementing these smoking bans.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Organophosphate flame retardants in dust collected from United States fire stations

Beverly Shen / Todd P. Whitehead / Ranjit Gill / Joginder Dhaliwal / F. Reber Brown / Myrto Petreas / Sharyle Patton / S. Katharine Hammond

Environment International, Vol 112, Iss , Pp 41-

2018 Volume 48

Abstract: Firefighters are exposed to chemicals during fire events and we previously demonstrated that fire station dust has high levels of polybrominated diphenyl ethers (PBDEs). In conducting the Fire Station Dust Study, we sought to further characterize the ... ...

Abstract	Firefighters are exposed to chemicals during fire events and we previously demonstrated that fire station dust has high levels of polybrominated diphenyl ethers (PBDEs). In conducting the Fire Station Dust Study, we sought to further characterize the chemicals to which firefighters could be exposed – measuring the emerging class of phosphorous-containing flame retardants (PFRs) in fire stations, for the first time, as well as PBDEs. Dust samples from 26 fire stations in five states were collected from vacuum-cleaner bags and analyzed for PFRs and PBDEs. PFR concentrations were found to be on the same order of magnitude as PBDE concentrations (maximum PFR: 218,000ng/g; maximum PBDE: 351,000ng/g). Median concentrations of tri-n-butyl phosphate (TNBP), tris (2-chloroisopropyl) phosphate (TCIPP), and tris(1,3-dichloroisopropyl)phosphate (TDCIPP) in dust from fire stations were higher than those previously reported in homes and other occupational settings around the world. Total PFR levels did not vary significantly among states. Levels of TDCIPP were higher in stations where vacuum cleaners were used to clean surfaces other than the floor. PBDE levels were comparable to those found in our previous study of 20 California fire stations and much higher than levels in California residences. PFR and PBDE levels in fire station dust are higher than in other occupational and residential settings, underscoring the need to identify and control sources of this contamination.
Keywords	Environmental sciences ; GE1-350
Subject code	551
Language	English
Publishing date	2018-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Flowering Poration—A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold

Katharine Hammond / Helen Lewis / Samantha Halliwell / Florie Desriac / Brunello Nardone / Jascindra Ravi / Bart W. Hoogenboom / Mathew Upton / Jeremy P. Derrick / Maxim G. Ryadnov

iScience, Vol 23, Iss 8, Pp 101423- (2020)

2020

Abstract: Summary: Bacteriocins are a distinct family of antimicrobial proteins postulated to porate bacterial membranes. However, direct experimental evidence of pore formation by these proteins is lacking. Here we report a multi-mode poration mechanism induced ... ...

Abstract	Summary: Bacteriocins are a distinct family of antimicrobial proteins postulated to porate bacterial membranes. However, direct experimental evidence of pore formation by these proteins is lacking. Here we report a multi-mode poration mechanism induced by four-helix bacteriocins, epidermicin NI01 and aureocin A53. Using a combination of crystallography, spectroscopy, bioassays, and nanoscale imaging, we established that individual two-helix segments of epidermicin retain antibacterial activity but each of these segments adopts a particular poration mode. In the intact protein these segments act synergistically to balance out antibacterial and hemolytic activities. The study sets a precedent of multi-mode membrane disruption advancing the current understanding of structure-activity relationships in pore-forming proteins.
Keywords	Biological Sciences ; Microbiology ; Structural Biology ; Science ; Q
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The impact on T-regulatory cell related immune responses in rural women exposed to polycyclic aromatic hydrocarbons (PAHs) in household air pollution in Gansu, China: A pilot investigation

Yao, Yueli / Dong Wang / Haitao Ma / Chengyun Li / Xiaoru Chang / Patrick Low / S. Katharine Hammond / Mary Ellen Turyk / Junling Wang / Sa Liu

Environmental research. 2019 June, v. 173

2019

Abstract: Previous studies found associations between impairments of immune functions and exposure to polycyclic aromatic hydrocarbons (PAHs) in ambient air pollution in the U. S. and China. However, the results remain inconclusive due to the limitations of these ... ...

Abstract	Previous studies found associations between impairments of immune functions and exposure to polycyclic aromatic hydrocarbons (PAHs) in ambient air pollution in the U. S. and China. However, the results remain inconclusive due to the limitations of these studies. In this study, we aimed to examine the direction and magnitude of immune changes related to PAH exposure from household air pollution among rural women living in Gansu, China. Healthy village women (n = 34) were recruited and enrolled in the study. Questionnaires were administered. Blood and urine samples were collected and analyzed during non-heating (September 2017, “summer”) and heating (January 2018, “winter”) seasons. Urinary 1-hydroxypyrene (1-OHP) was quantified as the biomarker of PAH exposure. To evaluate Treg cell related immune functions, we examined immunoglobulin E (IgE), percent of T-regulatory (Treg) cells, and gene expression of following: forkhead box transcription factor 3 (Foxp3), transforming growth factor-β (TGF-β), interleukin 10 (IL-10), and interleukin 35 (IL-35), composed of interleukin-12 alpha (IL-12α) and Epstein-Barr-virus-induced gene 3 (EBi3). Urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) was measured to evaluate oxidative DNA damage. The results showed that the concentration of 1-OHP increased from 0.90 to 17.4 μmol mol-Cr −1 from summer to winter (p < 0.001). Meanwhile, average percent of Treg cells decreased from 5.01% to 1.15% (p < 0.001); IgE and mRNA expressions of Foxp3, TGF-β, IL-10, IL-12α and EBi3 all significantly decreased (p < 0.001); Urinary 8-OHdG increased from 12.7 to 30.3 ng mg-Cr −1 (p < 0.001). The changes in 8-OHdG, Foxp3 and TGF-β were significantly associated with the increase of 1-OHP. The results suggested that we observed a substantial increase of PAH exposure in winter, which was significantly associated with the repression on Treg cell function and oxidative DNA damage. Exposure to PAHs in household air pollution possibly induced immune impairments among rural women in northwest China.
Keywords	DNA damage ; air pollution ; biomarkers ; blood ; genes ; immune response ; immunoglobulin E ; interleukin-10 ; interleukin-12 ; messenger RNA ; polycyclic aromatic hydrocarbons ; questionnaires ; rural population ; rural women ; summer ; transcription factors ; transforming growth factor beta ; urine ; villages ; winter ; China
Language	English
Dates of publication	2019-06
Size	p. 306-317.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2019.03.053
Database	NAL-Catalogue (AGRICOLA)

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Article: A pilot study comparing T-regulatory cell function among healthy children in different areas of Gansu, China

Gou, Panhong / Xiaoru Chang / Zhonghui Ye / Yueli Yao / Patton Khuu Nguyen / Sally Katharine Hammond / Junling Wang / Sa Liu

Environmental science and pollution research international. 2017 Oct., v. 24, no. 28

2017

Abstract: Immune system is critical to protecting human health from toxic substances. Our previously published research had found an important link between polycyclic aromatic hydrocarbons (PAHs) in ambient air and changes at the DNA level in immune cells that led ...

Abstract	Immune system is critical to protecting human health from toxic substances. Our previously published research had found an important link between polycyclic aromatic hydrocarbons (PAHs) in ambient air and changes at the DNA level in immune cells that led to impaired function of regulatory T (Treg) cells in children living in California, USA. But molecular and cellular pathways of these changes remain unclear. The present study aims to explore whether exposure to PAHs leads to changes in Treg cells functions of children living in Gansu, China, where ambient air pollution levels are much higher than those in California, and to explore potential mechanisms of PAH-induced immunological dysfunctions. Air pollutions in Lanzhou and Lintao, Gansu Province, were measured from December 2015 to June 2016. Healthy children were recruited from both cities and enrolled in this pilot study. Demographic information was collected by questionnaires. Blood samples were collected. Peripheral blood Treg cells were analyzed for Treg cells percentage by flow cytometry. Gene expression of forkhead box transcription factor 3 (Foxp3), transforming growth factor-β (TGF-β), and interleukin 35 (IL35) were examined by reverse transcription-polymerase chain reaction (RT-PCR). The results indicated PAH concentration (as sum of 16 PAHs) in Lintao was over two times higher than that was in Lanzhou (707 vs. 326 ng/m³), whereas PM₂.₅ concentration was comparable in two cities (55.3 in Lintao vs. 65.7 μg/m³ in Lanzhou). Notably, we observed lower gene expressions for Foxp3 (P < 0.05), IL35 (P < 0.05), and TGF-β, in children living in Lintao, suggesting an impairment of Treg cells function potentially associated with higher PAH exposure in Lintao. However, no significant difference was observed in Treg cells % among CD4⁺ T cells between Lanzhou and Lintao groups.
Keywords	CD4-positive T-lymphocytes ; DNA ; air ; air pollution ; blood sampling ; children ; cities ; flow cytometry ; human health ; interleukins ; polycyclic aromatic hydrocarbons ; questionnaires ; reverse transcriptase polymerase chain reaction ; toxic substances ; transcription factors ; transforming growth factor beta ; California ; China
Language	English
Dates of publication	2017-10
Size	p. 22579-22586.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ZDB-ID	1178791-0
ISSN	1614-7499 ; 0944-1344
ISSN (online)	1614-7499
ISSN	0944-1344
DOI	10.1007/s11356-017-9907-3
Database	NAL-Catalogue (AGRICOLA)

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Article: Organophosphate flame retardants in dust collected from United States fire stations

Shen, Beverly / Todd P. Whitehead / Ranjit Gill / Joginder Dhaliwal / F. Reber Brown / Myrto Petreas / Sharyle Patton / S. Katharine Hammond

Elsevier Ltd Environment international. 2018 Mar., v. 112

2018

Abstract	Firefighters are exposed to chemicals during fire events and we previously demonstrated that fire station dust has high levels of polybrominated diphenyl ethers (PBDEs). In conducting the Fire Station Dust Study, we sought to further characterize the chemicals to which firefighters could be exposed – measuring the emerging class of phosphorous-containing flame retardants (PFRs) in fire stations, for the first time, as well as PBDEs. Dust samples from 26 fire stations in five states were collected from vacuum-cleaner bags and analyzed for PFRs and PBDEs. PFR concentrations were found to be on the same order of magnitude as PBDE concentrations (maximum PFR: 218,000ng/g; maximum PBDE: 351,000ng/g). Median concentrations of tri-n-butyl phosphate (TNBP), tris (2-chloroisopropyl) phosphate (TCIPP), and tris(1,3-dichloroisopropyl)phosphate (TDCIPP) in dust from fire stations were higher than those previously reported in homes and other occupational settings around the world. Total PFR levels did not vary significantly among states. Levels of TDCIPP were higher in stations where vacuum cleaners were used to clean surfaces other than the floor. PBDE levels were comparable to those found in our previous study of 20 California fire stations and much higher than levels in California residences. PFR and PBDE levels in fire station dust are higher than in other occupational and residential settings, underscoring the need to identify and control sources of this contamination.
Keywords	air pollution ; bags ; dust ; fire fighters ; flame retardants ; organophosphorus compounds ; phosphates ; polybrominated diphenyl ethers ; residential areas ; vacuum cleaners ; California
Language	English
Dates of publication	2018-03
Size	p. 41-48.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2017.12.009
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Ischemic Heart Disease Incidence in Relation to Fine versus Total Particulate Matter Exposure in a U.S. Aluminum Industry Cohort.

Andreas M Neophytou / Elizabeth M Noth / Sa Liu / Sadie Costello / S Katharine Hammond / Mark R Cullen / Ellen A Eisen

PLoS ONE, Vol 11, Iss 6, p e

2016 Volume 0156613

Abstract: Ischemic heart disease (IHD) has been linked to exposures to airborne particles with an aerodynamic diameter <2.5 μm (PM2.5) in the ambient environment and in occupational settings. Routine industrial exposure monitoring, however, has traditionally ... ...

Abstract	Ischemic heart disease (IHD) has been linked to exposures to airborne particles with an aerodynamic diameter <2.5 μm (PM2.5) in the ambient environment and in occupational settings. Routine industrial exposure monitoring, however, has traditionally focused on total particulate matter (TPM). To assess potential benefits of PM2.5 monitoring, we compared the exposure-response relationships between both PM2.5 and TPM and incidence of IHD in a cohort of active aluminum industry workers. To account for the presence of time varying confounding by health status we applied marginal structural Cox models in a cohort followed with medical claims data for IHD incidence from 1998 to 2012. Analyses were stratified by work process into smelters (n = 6,579) and fabrication (n = 7,432). Binary exposure was defined by the 10th-percentile cut-off from the respective TPM and PM2.5 exposure distributions for each work process. Hazard Ratios (HR) comparing always exposed above the exposure cut-off to always exposed below the cut-off were higher for PM2.5, with HRs of 1.70 (95% confidence interval (CI): 1.11-2.60) and 1.48 (95% CI: 1.02-2.13) in smelters and fabrication, respectively. For TPM, the HRs were 1.25 (95% CI: 0.89-1.77) and 1.25 (95% CI: 0.88-1.77) for smelters and fabrication respectively. Although TPM and PM2.5 were highly correlated in this work environment, results indicate that, consistent with biologic plausibility, PM2.5 is a stronger predictor of IHD risk than TPM. Cardiovascular risk management in the aluminum industry, and other similar work environments, could be better guided by exposure surveillance programs monitoring PM2.5.
Keywords	Medicine ; R ; Science ; Q
Subject code	600
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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