Publications by authors named "Sarah Becker"

33 Publications

The geographic disparity of historical greenhouse emissions and projected climate change.

Sci Adv 2021 Jul 14;7(29). Epub 2021 Jul 14.

Monterey Bay Aquarium, 886 Cannery Row, Monterey, CA 93940, USA.

One challenge in climate change communication is that the causes and impacts of global warming are unrelated at local spatial scales. Using high-resolution datasets of historical anthropogenic greenhouse emissions and an ensemble of 21st century surface temperature projections, we developed a spatially explicit index of local climate disparity. This index identifies positive (low emissions, large temperature shifts) and negative disparity regions (high emissions, small temperature shifts), with global coverage. Across all climate change projections we analyzed, 99% of the earth's surface area has a positive index value. This result underscores that while emissions are geographically concentrated, warming is globally widespread. From our index, the regions of the greatest positive disparity appear concentrated in the polar arctic, Central Asia, and Africa with negative disparity regions in western Europe, Southeast Asia, and eastern North America. Straightforward illustrations of this complex relationship may inform on equity, enhance public understanding, and increase collective global action.
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http://dx.doi.org/10.1126/sciadv.abe4342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279500PMC
July 2021

Personalized Radiation Attenuating Materials for Gastrointestinal Mucosal Protection.

Adv Sci (Weinh) 2021 06 27;8(12):2100510. Epub 2021 Apr 27.

Division of Gastroenterology Brigham and Women's Hospital Harvard Medical School 75 Francis St. Boston MA 02115 USA.

Cancer patients undergoing therapeutic radiation routinely develop injury of the adjacent gastrointestinal (GI) tract mucosa due to treatment. To reduce radiation dose to critical GI structures including the rectum and oral mucosa, 3D-printed GI radioprotective devices composed of high-Z materials are generated from patient CT scans. In a radiation proctitis rat model, a significant reduction in crypt injury is demonstrated with the device compared to without ( < 0.0087). Optimal device placement for radiation attenuation is further confirmed in a swine model. Dosimetric modeling in oral cavity cancer patients demonstrates a 30% radiation dose reduction to the normal buccal mucosa and a 15.2% dose reduction in the rectum for prostate cancer patients with the radioprotectant material in place compared to without. Finally, it is found that the rectal radioprotectant device is more cost-effective compared to a hydrogel rectal spacer. Taken together, these data suggest that personalized radioprotectant devices may be used to reduce GI tissue injury in cancer patients undergoing therapeutic radiation.
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http://dx.doi.org/10.1002/advs.202100510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224439PMC
June 2021

Variations in strain affect friction and microstructure evolution in copper under a reciprocating tribological load.

J Mater Res 2021 Mar 25;36(4):970-981. Epub 2021 Jan 25.

Institute for Applied Materials (IAM), Karlsruhe Institute of Technology (KIT), Kaiserstrasse 12, 76131 Karlsruhe, Germany.

The microstructure of the materials constituting a metallic frictional contact strongly influence tribological performance. Being able to tailor friction and wear is challenging due to the complex microstructure evolution associated with tribological loading. Here, we investigate the effect of the strain distribution on these processes. High-purity copper plates were morphologically surface textured with two parallel rectangles - referred to as membranes - over the entire sample length by micro-milling. By keeping the width of these membranes constant and only varying their height, reciprocating tribological loading against sapphire discs resulted in different elastic and plastic strains. Finite element simulations were carried out to evaluate the strain distribution in the membranes. It was found that the maximum elastic strain increases with decreasing membrane stiffness. The coefficient of friction decreases with increasing membrane aspect ratio. By analyzing the microstructure and local crystallographic orientation, we found that both show less change with decreasing membrane stiffness.
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http://dx.doi.org/10.1557/s43578-020-00050-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610874PMC
March 2021

Awaking to Mutual, Reciprocal Need in Plague and Epidemic Disease: The Origins of Early Christian Health Care.

Authors:
Sarah E Becker

Linacre Q 2021 May 13;88(2):163-174. Epub 2020 Oct 13.

Oakland University William Beaumont School of Medicine in Rochester, MI, USA.

While the early Christian Church demonstrates a deep desire to relieve physical suffering, the Greco-Roman world in which it developed lacked the same impetus to respond to human need, especially in the context of epidemic or communicable disease. Christianity's dedication to health care, and its belief that assisting the sick constituted an absolute obligation, distinguished early Christianity from its contemporary cultural milieu which regularly ignored and excluded the sick. The novelty of the Christian approach to healing can be traced to the early church's unique recognition of human need. This vision of human need, which ultimately replaced the secular Greco-Roman emphasis on reciprocal philanthropy and providing assistance only to the worthy, is clearly exemplified in the life of Christ, in responses to plague and in the writings of John Chrysostom and the Cappadocian Fathers Basil the Great, Gregory of Nyssa, and Gregory of Nazianzus. An analysis of these sources demonstrates that the early Christian Church viewed the sick not only as persons to be assisted insofar as they shared a common human nature but also individuals necessary for the salvation of the broader community as a whole. The early church's emphasis on reciprocal interdependence between healthy and sick eliminated the boundaries traditionally established between these two groups and transformed long-standing notions of contagious disease. Ultimately, the development of these attitudes toward the sick originates in a deeper truth which underlies the Christian healthcare tradition both in the ancient world and in the modern era: humanity's profound and mutual need of God, before whom all are spiritually ill.
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http://dx.doi.org/10.1177/0024363920962958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033497PMC
May 2021

Prevalence and characteristics of campus-based employee wellness programs among United States accredited colleges and universities.

Work 2021 ;68(4):1049-1057

Department of Occupational Therapy, University of Alabama at Birmingham, Birmingham, AL, USA.

Background: Employee wellness programs (EWPs) aim to support positive changes in employees' modifiable behavioral health risk factors for disease prevention and management.

Objective: This study described the prevalence and characteristics of EWPs in US accredited college and university campuses.

Methods: Identification of the prevalence of EWPs and programming activities offered in 3039 accredited higher education institutions/campuses, and characteristics of these institutions/campuses were conducted, mainly through searching the institution's web page.

Results: Overall, 36%of the institutions/campuses offered EWPs, with a significantly larger percentage of 4-year public colleges/universities providing EWPs and wellness programming activities than the 4-year private colleges/universities and community colleges. When limiting the institutions/campuses to 4-year colleges and universities with at least 500 employees, the percentage of these institutions/campuses offering EWPs increased to 57.7%, which was comparable to the findings in the literature. The percentage of the institutions/campuses offering wellness programming activities ranged from 18.1%for injury prevention and ergonomics to 30.2%for stress management. The percentage of institutions/campuses offering injury prevention and ergonomics was significantly lower than the percentage of institutions/campuses offering other typical wellness activities.

Conclusions: The prevalence of EWPs offered in accredited college and university campuses do not meet the national goal of 75%, which was set by Healthy People 2010.
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http://dx.doi.org/10.3233/WOR-213435DOI Listing
June 2021

Prospective Evaluation of the Transparent, Elastomeric, Adaptable, Long-Lasting (TEAL) Respirator.

ACS Pharmacol Transl Sci 2020 Dec 10;3(6):1076-1082. Epub 2020 Nov 10.

Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.

N95 filtering facepiece respirators (FFR) and surgical masks are essential in reducing airborne disease transmission, particularly during the COVID-19 pandemic. However, currently available FFR's and masks have major limitations, including masking facial features, waste, and integrity after decontamination. In a multi-institutional trial, we evaluated a transparent, elastomeric, adaptable, long-lasting (TEAL) respirator to evaluate success of qualitative fit test with user experience and biometric evaluation of temperature, respiratory rate, and fit of respirator using a novel sensor. There was a 100% successful fit test among participants, with feedback demonstrating excellent or good fit (90% of participants), breathability (77.5%), and filter exchange (95%). Biometric testing demonstrated significant differences between exhalation and inhalation pressures among a poorly fitting respirator, well-fitting respirator, and the occlusion of one filter of the respirator. We have designed and evaluated a transparent elastomeric respirator and a novel biometric feedback system that could be implemented in the hospital setting.
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http://dx.doi.org/10.1021/acsptsci.0c00157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671102PMC
December 2020

Menopause, the gut microbiome, and weight gain: correlation or causation?

Menopause 2020 11 23;28(3):327-331. Epub 2020 Nov 23.

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.

Abstract: The gut microbiome is a key regulator of metabolism and influences the metabolism of estrogens, however, the microbiome's role in the changes in body composition and metabolic risk factors experienced by menopausal women remains largely unexplored. Menopause has been shown to alter the gut microbiome, and rodent studies suggest that microbiome changes postovariectomy are associated with increased adiposity, decreased metabolic rate, and insulin resistance, changes attenuated by estrogen administration. Given these data, a deeper understanding of the gut microbiome's relationship to menopause-induced changes in body composition and metabolism is warranted and may offer opportunity for novel therapeutic interventions.The microbiome is central to both systemic and estrogen metabolism, and is altered by the menopausal transition, suggesting an important role of the microbiome in the increased metabolic risk faced by menopausal women. Although additional research is needed to establish a causal link, the interrelationship between menopause and the gut microbiome may represent a new frontier to address menopause-related metabolic risk.
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http://dx.doi.org/10.1097/GME.0000000000001702DOI Listing
November 2020

RNA-Seq Time Series of Bud Development Reveals Correlation of Expression Patterns with the Local Temperature Profile.

Plants (Basel) 2020 Nov 12;9(11). Epub 2020 Nov 12.

Genetics and Genomics of Plants, Faculty of Biology and Center for Biotechnology (CeBiTec), Bielefeld University, 33615 Bielefeld, Germany.

Plants display sophisticated mechanisms to tolerate challenging environmental conditions and need to manage their ontogenesis in parallel. Here, we set out to generate an RNA-Seq time series dataset throughout grapevine () early bud development. The expression of the developmental regulator served as an indicator of the progression of development. We investigated the impact of changing temperatures on gene expression levels during the time series and detected a correlation between increased temperatures and a high expression level of genes encoding heat-shock proteins. The dataset also allowed the exemplary investigation of expression patterns of genes from three transcription factor (TF) gene families, namely MADS-box, WRKY, and R2R3-MYB genes. Inspection of the expression profiles from all three TF gene families indicated that a switch in the developmental program takes place in July which coincides with increased expression of the bud dormancy marker gene .
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http://dx.doi.org/10.3390/plants9111548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698159PMC
November 2020

Plasmid Acquisition Alters Vancomycin Susceptibility in Clostridioides difficile.

Gastroenterology 2021 02 14;160(3):941-945.e8. Epub 2020 Nov 14.

Division of Gastroenterology and Hepatology, Department of Medicine, Rochester, Minnesota; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota. Electronic address:

The increasing incidence of primary and recurring Clostridioides difficile infections (CDI), which evade current treatment strategies, reflects the changing biology of C difficile. Here, we describe a putative plasmid-mediated mechanism potentially driving decreased sensitivity of C difficile to vancomycin treatment. We identified a broad host range transferable plasmid in a C difficile strain associated with lack of adequate response to vancomycin treatment. The transfer of this plasmid to a vancomycin-susceptible C difficile isolate decreased its susceptibility to vancomycin in vitro and resulted in more severe disease in a humanized mouse model. Our findings suggest plasmid acquisition in the gastrointestinal tract to be a possible mechanism underlying vancomycin treatment failure in patients with CDI, but further work is needed to characterize the mechanism by which plasmid genes determine vancomycin susceptibility in C difficile.
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http://dx.doi.org/10.1053/j.gastro.2020.10.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878333PMC
February 2021

SSAT State-of-the-Art Conference: Advancements in the Microbiome.

J Gastrointest Surg 2021 Jul;25(7):1885-1895

Department of General Surgery, Cleveland Clinic, Cleveland, OH, 44195, USA.

The microbiome plays a major role in human physiology by influencing obesity, inducing inflammation, and impacting cancer therapies. During the 60th Annual Meeting of the Society of the Alimentary Tract (SSAT) at the State-of-the-Art Conference, experts in the field discussed the influence of the microbiome. This paper is a summary of the influence of the microbiome on obesity, inflammatory bowel disease, pancreatic cancer, cancer therapies, and gastrointestinal optimization. This review shows how the microbiome plays an important role in the development of diseases and surgical complications. Future studies are needed in targeting the gut microbiome to develop individualized therapies.
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http://dx.doi.org/10.1007/s11605-020-04551-4DOI Listing
July 2021

Injection Molded Autoclavable, Scalable, Conformable (iMASC) system for aerosol-based protection: a prospective single-arm feasibility study.

BMJ Open 2020 07 7;10(7):e039120. Epub 2020 Jul 7.

Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts, USA

Objective: To develop and test a new reusable, sterilisable N95 filtering facepiece respirator (FFR)-comparable face mask, known as the Injection Molded Autoclavable, Scalable, Conformable (iMASC) system, given the dire need for personal protective equipment within healthcare settings during the COVID-19 pandemic.

Design: Single-arm feasibility study.

Setting: Emergency department and outpatient oncology clinic.

Participants: Healthcare workers who have previously undergone N95 fit testing.

Interventions: Fit testing of new iMASC system.

Primary And Secondary Outcome Measures: Primary outcome is success of fit testing using an Occupational Safety and Health Administration (OSHA)-approved testing method, and secondary outcomes are user experience with fit, breathability and filter replacement.

Results: Twenty-four subjects were recruited to undergo fit testing, and the average age of subjects was 41 years (range of 21-65 years) with an average body mass index of 26.5 kg/m. The breakdown of participants by profession was 46% nurses (n=11), 21% attending physicians (n=5), 21% resident physicians (n=5) and 12% technicians (n=3). Of these participants, four did not perform the fit testing due to the inability to detect saccharin solution on premask placement sensitivity test, lack of time and inability to place mask over hair. All participants (n=20) who performed the fit test were successfully fitted for the iMASC system using an OSHA-approved testing method. User experience with the iMASC system, as evaluated using a Likert scale with a score of 1 indicating excellent and a score of 5 indicating very poor, demonstrated an average fit score of 1.75, breathability of 1.6, and ease of replacing the filter on the mask was scored on average as 2.05.

Conclusions: The iMASC system was shown to successfully fit multiple different face sizes and shapes using an OSHA-approved testing method. These data support further certification testing needed for use in the healthcare setting.
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http://dx.doi.org/10.1136/bmjopen-2020-039120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342850PMC
July 2020

The Rho guanine nucleotide exchange factor Trio is required for neural crest cell migration and interacts with Dishevelled.

Development 2020 05 22;147(10). Epub 2020 May 22.

Philipps-Universität Marburg, Faculty of Biology, Molecular Embryology, 35043 Marburg, Germany

Directional migration during embryogenesis and tumor progression faces the challenge that numerous external signals need to converge to precisely control cell movement. The Rho guanine exchange factor (GEF) Trio is especially well suited to relay signals, as it features distinct catalytic domains to activate Rho GTPases. Here, we show that Trio is required for cranial neural crest (NC) cell migration and cartilage formation. Trio cell-autonomously controls protrusion formation of NC cells and Trio morphant NC cells show a blebbing phenotype. Interestingly, the Trio GEF2 domain is sufficient to rescue protrusion formation and migration of Trio morphant NC cells. We show that this domain interacts with the DEP/C-terminus of Dishevelled (DVL). DVL - but not a deletion construct lacking the DEP domain - is able to rescue protrusion formation and migration of Trio morphant NC cells. This is likely mediated by activation of Rac1, as we find that DVL rescues Rac1 activity in Trio morphant embryos. Thus, our data provide evidence for a novel signaling pathway, whereby Trio controls protrusion formation of cranial NC cells by interacting with DVL to activate Rac1.
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http://dx.doi.org/10.1242/dev.186338DOI Listing
May 2020

Effect of stevia on the gut microbiota and glucose tolerance in a murine model of diet-induced obesity.

FEMS Microbiol Ecol 2020 06;96(6)

Department of Biology, Williams College, Science Center South Building Room 222, Williamstown, MA, USA 01267.

Artificial sweeteners have been shown to induce glucose intolerance by altering the gut microbiota; however, little is known about the effect of stevia. Here, we investigate whether stevia supplementation induces glucose intolerance by altering the gut microbiota in mice, hypothesizing that stevia would correct high fat diet-induced glucose intolerance and alter the gut microbiota. Mice were split into four treatment groups: low fat, high fat, high fat + saccharin and high fat + stevia. After 10 weeks of treatment, mice consuming a high fat diet (60% kcal from fat) developed glucose intolerance and gained more weight than mice consuming a low fat diet. Stevia supplementation did not impact body weight or glucose intolerance. Differences in species richness and relative abundances of several phyla were observed in low fat groups compared to high fat, stevia and saccharin. We identified two operational taxonomic groups that contributed to differences in beta-diversity between the stevia and saccharin groups: Lactococcus and Akkermansia in females and Lactococcus in males. Our results demonstrate that stevia does not rescue high fat diet-induced changes in glucose tolerance or the microbiota, and that stevia results in similar alterations to the gut microbiota as saccharin when administered in concordance with a high fat diet.
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http://dx.doi.org/10.1093/femsec/fiaa079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233940PMC
June 2020

Implied Consent in Treating Psychiatric Emergencies.

Front Psychiatry 2020 13;11:127. Epub 2020 Mar 13.

Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, New York, NY, United States.

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http://dx.doi.org/10.3389/fpsyt.2020.00127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082920PMC
March 2020

Poly(adenosine diphosphate ribose) polymerase inhibitors induce autophagy-mediated drug resistance in ovarian cancer cells, xenografts, and patient-derived xenograft models.

Cancer 2020 02 12;126(4):894-907. Epub 2019 Nov 12.

Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors exhibit promising activity against ovarian cancers, but their efficacy can be limited by acquired drug resistance. This study explores the role of autophagy in regulating the sensitivity of ovarian cancer cells to PARP inhibitors.

Methods: Induction of autophagy was detected by punctate LC3 fluorescence staining, LC3I to LC3II conversion on Western blot analysis, and electron microscopy. Enhanced growth inhibition and apoptosis were observed when PARP inhibitors were used with hydroxychloroquine, chloroquine (CQ), or LYS05 to block the hydrolysis of proteins and lipids in autophagosomes or with small interfering RNA against ATG5 or ATG7 to prevent the formation of autophagosomes. The preclinical efficacy of the combination of CQ and olaparib was evaluated with a patient-derived xenograft (PDX) and the OVCAR8 human ovarian cancer cell line.

Results: Four PARP inhibitors (olaparib, niraparib, rucaparib, and talazoparib) induced autophagy in a panel of ovarian cancer cells. Inhibition of autophagy with CQ enhanced the sensitivity of ovarian cancer cells to PARP inhibitors. In vivo, olaparib and CQ produced additive growth inhibition in OVCAR8 xenografts and a PDX. Olaparib inhibited PARP activity, and this led to increased reactive oxygen species (ROS) and an accumulation of γ-H2AX. Inhibition of autophagy also increased ROS and γ-H2AX and enhanced the effect of olaparib on both entities. Treatment with olaparib increased phosphorylation of ATM and PTEN while decreasing the phosphorylation of AKT and mTOR and inducing autophagy.

Conclusions: PARP inhibitor-induced autophagy provides an adaptive mechanism of resistance to PARP inhibitors in cancer cells with wild-type BRCA, and a combination of PARP inhibitors with CQ or other autophagy inhibitors could improve outcomes for patients with ovarian cancer.
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http://dx.doi.org/10.1002/cncr.32600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992526PMC
February 2020

Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.

Nat Commun 2019 08 19;10(1):3731. Epub 2019 Aug 19.

Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade gliomas, a strikingly higher proportion of the PA cancer cells exhibit a differentiated, astrocyte-like phenotype. A smaller proportion of cells exhibit a progenitor-like phenotype with evidence of proliferation. These express a mitogen-activated protein kinase (MAPK) programme that was absent from higher-grade gliomas. Immune cells, especially microglia, comprise 40% of all cells in the PAs and account for differences in bulk expression profiles between tumor locations and subtypes. These data indicate that MAPK signaling is restricted to relatively undifferentiated cancer cells in PA, with implications for investigational therapies directed at this pathway.
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http://dx.doi.org/10.1038/s41467-019-11493-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700116PMC
August 2019

An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma.

Cell 2019 08 18;178(4):835-849.e21. Epub 2019 Jul 18.

Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, 1090, Austria.

Diverse genetic, epigenetic, and developmental programs drive glioblastoma, an incurable and poorly understood tumor, but their precise characterization remains challenging. Here, we use an integrative approach spanning single-cell RNA-sequencing of 28 tumors, bulk genetic and expression analysis of 401 specimens from the The Cancer Genome Atlas (TCGA), functional approaches, and single-cell lineage tracing to derive a unified model of cellular states and genetic diversity in glioblastoma. We find that malignant cells in glioblastoma exist in four main cellular states that recapitulate distinct neural cell types, are influenced by the tumor microenvironment, and exhibit plasticity. The relative frequency of cells in each state varies between glioblastoma samples and is influenced by copy number amplifications of the CDK4, EGFR, and PDGFRA loci and by mutations in the NF1 locus, which each favor a defined state. Our work provides a blueprint for glioblastoma, integrating the malignant cell programs, their plasticity, and their modulation by genetic drivers.
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http://dx.doi.org/10.1016/j.cell.2019.06.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703186PMC
August 2019

Densities and drivers of sea turtle populations across Pacific coral reef ecosystems.

PLoS One 2019 24;14(4):e0214972. Epub 2019 Apr 24.

Monterey Bay Aquarium, Monterey, California, United States of America.

Sea turtle populations are often assessed at the regional to sub-basin scale from discrete indices of nesting abundance. While this may be practical and sometimes effective, widespread in-water surveys may enhance assessments by including additional demographics, locations, and revealing emerging population trends. Here, we describe sea turtle observations from 13 years of towed-diver surveys across 53 coral islands, atolls, and reefs in the Central, West, and South Pacific. These surveys covered more than 7,300 linear km, and observed more than 3,400 green (Chelonia mydas) and hawksbill (Eretmochelys imbricata) sea turtles. From these data, we estimated sea turtle densities, described trends across space and time, and modelled the influence of environmental and anthropogenic drivers. Both species were patchily distributed across spatial scales, and green turtles were 11 times more abundant than hawksbills. The Pacific Remote Island Areas had the highest densities of greens (3.62 turtles km-1, Jarvis Island), while American Samoa had the most hawksbills (0.12 turtles km-1, Ta'u Island). The Hawaiian Islands had the lowest turtle densities (island ave = 0.07 turtles km-1) yet the highest annual population growth (μ = 0.08, σ = 0.22), suggesting extensive management protections can yield positive conservation results. Densities peaked at 27.5°C SST, in areas of high productivity and low human impact, and were consistent with patterns of historic overexploitation. Though such intensive surveys have great value, they are logistically demanding and therefore have an uncertain budget and programmatic future. We hope the methods we described here may be applied to future comparatively low-cost surveys either with autonomous vehicles or with environmental DNA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214972PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481790PMC
December 2019

Prospective study of serum and ionized magnesium pharmacokinetics in the treatment of children with severe acute asthma.

Eur J Clin Pharmacol 2019 Jan 26;75(1):59-66. Epub 2018 Sep 26.

Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.

Purpose: Intravenous (IV) magnesium sulfate (MgSO) is clinically useful as adjunct therapy in treating acute asthma exacerbations. Despite its clinical utility, the disposition of magnesium in children is poorly described. The purpose of this study is to describe the pharmacokinetics (PK) of ionized and total serum magnesium following IV MgSO administration in children with severe acute asthma.

Methods: Thirty-two children receiving 50 mg/kg IV MgSO for acute asthma exacerbations at Primary Children's Hospital in Salt Lake City, UT, were prospectively enrolled in the study. Blood samples were collected before, as well as 30 min and 2 h after each child's IV MgSO dose, and used to determine total serum and ionized magnesium concentrations. The collected data were analyzed using population PK techniques using NONMEM® software.

Results: Total serum magnesium concentrations were used to externally validate our previously published model constructed with retrospective data (median prediction error 10.3%, median absolute prediction error 18.1%). The mean (%CV) observed endogenous ionized magnesium concentration was calculated to be 6.0 mg/L (12%), approximately one third of the same value for endogenous total serum magnesium (17.6 mg/L (22%)) in this dataset. Weight was a significant predictor of both clearance and volume in a population PK model describing ionized magnesium concentrations. No adverse events were observed in this pediatric cohort.

Conclusions: This prospective study supports and extends our previous PK analysis of total serum magnesium concentrations. Ionized and total serum magnesium followed similar PK profiles following IV MgSO administration in children. A single bolus infusion of IV MgSO was safe in this small sample of children receiving it for acute asthma.
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http://dx.doi.org/10.1007/s00228-018-2557-7DOI Listing
January 2019

Exploring the Influence of Hookup Culture on Female and Male Rape Myths.

J Interpers Violence 2021 05 22;36(9-10):NP5496-NP5520. Epub 2018 Sep 22.

Louisiana State University, Baton Rouge, USA.

The present study systematically assesses the influence of hookup culture endorsement on the acceptance of female rape myths (i.e., false, stereotypical, or prejudicial beliefs regarding sexual assault involving survivors) and male rape myths (i.e., false, stereotypical, or prejudicial beliefs about sexual assault involving survivors). Multivariate regression analyses were conducted to assess the primary hypotheses that a particular form of hookup culture endorsement (i.e., the belief that hookups elevate an individual's social status) would act as the primary predictor of male and female rape myth acceptance among a sample of 376 U.S. college students. As with prior research, a complex relationship emerged for both male and female rape mythology in which acceptance increases or decreases based upon the form of hookup culture endorsement examined, as the endorsement of beliefs reflecting heterosexual power dynamics (e.g., harmlessness and status attainment) functioned as positive predictors of rape myth acceptance, while beliefs challenging such assumptions (e.g., sexual freedom) served to decrease rape myth acceptance. Results supported the primary hypotheses that beliefs concerning hookups and status attainment would be the largest predictor of male rape myth acceptance and female rape myth acceptance. Consistent with prior research, the predictive power of gender and religiosity was initially significant across both male and female rape myth acceptance yet diminished when controlling for levels of hookup culture endorsement. Furthermore, analyses indicated gender differences among the influences of hookup culture endorsement for , as even though beliefs concerning status served as an aggravating factor for female rape myth acceptance, beliefs concerning sexual freedom served as a mitigating factor for women only.
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http://dx.doi.org/10.1177/0886260518801021DOI Listing
May 2021

New Challenge, New Motivation? Goal Orientation Development in Graduates of Higher Track Schools and Their Peers in Vocational Training.

Front Psychol 2018 3;9:1371. Epub 2018 Aug 3.

Department of Educational Research, University of Bamberg, Bamberg, Germany.

Many studies have demonstrated a decrease in mastery-approach goals and an increase in performance-approach goals after students' transition from primary to secondary education. A theoretical explanation for this phenomenon is a deteriorating fit between a learner's needs and environmental conditions. The purpose of this study was to further examine the development of students' goal orientation after they graduated from a higher track secondary school and transitioned to university or vocational training as compared with peers who chose vocational training earlier. We also examined the fit between the students' needs and the conditions in the new educational context to elaborate on the differential fit hypothesis. Data from 487 students and trainees who participated in a German longitudinal school study were available for our analyses. Latent change score models indicated a significant increase in mastery-approach and a decrease in performance-approach goals for higher track graduates after they transitioned to a new educational context, paralleled by an adequate fit between the learners' needs and the new educational context. For their peers who started vocational training early, mastery-approach goals seem to remain stable, whereas performance-approach goals decreased over time. The results are discussed in the context of the stage-environment fit theory.
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http://dx.doi.org/10.3389/fpsyg.2018.01371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085573PMC
August 2018

Specific Interactions Measured by AFM on Living Cells between Peroxiredoxin-5 and TLR4: Relevance for Mechanisms of Innate Immunity.

Cell Chem Biol 2018 05 15;25(5):550-559.e3. Epub 2018 Mar 15.

Université catholique de Louvain, Institut des Sciences de la Vie (ISV), 1348 Louvain-la-Neuve, Belgium. Electronic address:

Inflammation is a pathophysiological response of innate immunity to infection or tissue damage. This response is among others triggered by factors released by damaged or dying cells, termed damage-associated molecular pattern (DAMP) molecules that act as danger signals. DAMPs interact with pattern recognition receptors (PRRs) to contribute to the induction of inflammation. However, how released peroxiredoxins (PRDXs) are able to activate PRRs, such as Toll-like receptors (TLRs), remains elusive. Here, we used force-distance curve-based atomic force microscopy to investigate the molecular mechanisms by which extracellular human PRDX5 can activate a proinflammatory response. Single-molecule experiments demonstrated that PRDX5 binds to purified TLR4 receptors, on macrophage-differentiated THP-1 cells, and on human TLR4-transfected CHO cells. These findings suggest that extracellular PRDX5 can specifically trigger a proinflammatory response. Moreover, our work also revealed that PRDX5 binding induces a cellular mechanoresponse. Collectively, this study provides insights into the role of extracellular PRDX5 in innate immunity.
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http://dx.doi.org/10.1016/j.chembiol.2018.02.006DOI Listing
May 2018

Natural and induced direct reprogramming: mechanisms, concepts and general principles-from the worm to vertebrates.

Curr Opin Genet Dev 2016 10 28;40:154-163. Epub 2016 Sep 28.

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR7104, INSERM U964, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch Cu Strasbourg, France. Electronic address:

Elucidating the mechanisms underlying cell fate determination, cell identity maintenance and cell reprogramming in vivo is one of the main challenges in today's science. Such knowledge of fundamental importance will further provide new leads for early diagnostics and targeted therapy approaches both in regenerative medicine and cancer research. This review focuses on recent mechanistic findings and factors that influence the differentiated state of cells in direct reprogramming events, aka transdifferentiation. In particular, we will look at the mechanistic and conceptual advances brought by the use of the nematode Caenorhabditis elegans and highlight common themes across phyla.
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http://dx.doi.org/10.1016/j.gde.2016.06.014DOI Listing
October 2016

Cadherin-11 localizes to focal adhesions and promotes cell-substrate adhesion.

Nat Commun 2016 Mar 8;7:10909. Epub 2016 Mar 8.

Zoological Institute, Cell and Developmental Biology, Karlsruhe Institute of Technology (KIT), Kaiserstrasse 12, 76131 Karlsruhe, Germany.

Cadherin receptors have a well-established role in cell-cell adhesion, cell polarization and differentiation. However, some cadherins also promote cell and tissue movement during embryonic development and tumour progression. In particular, cadherin-11 is upregulated during tumour and inflammatory cell invasion, but the mechanisms underlying cadherin-11 stimulated cell migration are still incompletely understood. Here, we show that cadherin-11 localizes to focal adhesions and promotes adhesion to fibronectin in Xenopus neural crest, a highly migratory embryonic cell population. Transfected cadherin-11 also localizes to focal adhesions in different mammalian cell lines, while endogenous cadherin-11 shows focal adhesion localization in primary human fibroblasts. In focal adhesions, cadherin-11 co-localizes with β1-integrin and paxillin and physically interacts with the fibronectin-binding proteoglycan syndecan-4. Adhesion to fibronectin mediated by cadherin-11/syndecan-4 complexes requires both the extracellular domain of syndecan-4, and the transmembrane and cytoplasmic domains of cadherin-11. These results reveal an unexpected role of a classical cadherin in cell-matrix adhesion during cell migration.
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http://dx.doi.org/10.1038/ncomms10909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786774PMC
March 2016

Multiple Roles of Peroxiredoxins in Inflammation.

Mol Cells 2016 Jan 25;39(1):60-4. Epub 2016 Jan 25.

Group of Animal Molecular and Cellular Biology, Institut des Sciences de la Vie (ISV), Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium.

Inflammation is a pathophysiological response to infection or tissue damage during which high levels of reactive oxygen and nitrogen species are produced by phagocytes to kill microorganisms. Reactive oxygen and nitrogen species serve also in the complex regulation of inflammatory processes. Recently, it has been proposed that peroxiredoxins may play key roles in innate immunity and inflammation. Indeed, peroxiredoxins are evolutionarily conserved peroxidases able to reduce, with high rate constants, hydrogen peroxide, alkyl hydroperoxides and peroxynitrite which are generated during inflammation. In this minireview, we point out different possible roles of peroxiredoxins during inflammatory processes such as cytoprotective enzymes against oxidative stress, modulators of redox signaling, and extracellular pathogen- or damage-associated molecular patterns. A better understanding of peroxiredoxin functions in inflammation could lead to the discovery of new therapeutic targets.
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http://dx.doi.org/10.14348/molcells.2016.2341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749876PMC
January 2016

ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site.

Dev Biol 2016 07 21;415(2):383-390. Epub 2015 Jul 21.

Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.

The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell-cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo.
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http://dx.doi.org/10.1016/j.ydbio.2015.07.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721947PMC
July 2016

Antioxidant cytoprotection by peroxisomal peroxiredoxin-5.

Free Radic Biol Med 2015 Jul 13;84:215-226. Epub 2015 Mar 13.

Group of Animal Molecular and Cellular Biology, Institut des Sciences de la Vie, Université Catholique de Louvain, 1348 Louvain-la-Neuve, Belgium. Electronic address:

Peroxiredoxin-5 (PRDX5) is a thioredoxin peroxidase that reduces hydrogen peroxide, alkyl hydroperoxides, and peroxynitrite. This enzyme is present in the cytosol, mitochondria, peroxisomes, and nucleus in human cells. Antioxidant cytoprotective functions have been previously documented for cytosolic, mitochondrial, and nuclear mammalian PRDX5. However, the exact function of PRDX5 in peroxisomes is still not clear. The aim of this work was to determine the function of peroxisomal PRDX5 in mammalian cells and, more specifically, in glial cells. To study the role of PRDX5 in peroxisomes, the endogenous expression of PRDX5 in murine oligodendrocyte 158N cells was silenced by RNA interference. In addition, human PRDX5 was also overexpressed in peroxisomes using a vector coding for human PRDX5, whose unconventional peroxisomal targeting sequence 1 (PTS1; SQL) was replaced by the prototypical PTS1 SKL. Stable 158N clones were obtained. The antioxidant cytoprotective function of peroxisomal PRDX5 against peroxisomal and mitochondrial KillerRed-mediated reactive oxygen species production as well as H2O2 was examined using MTT viability assays, roGFP2, and C11-BOBIPY probes. Altogether our results show that peroxisomal PRDX5 protects 158N oligodendrocytes against peroxisomal and mitochondrial KillerRed- and H2O2-induced oxidative stress.
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http://dx.doi.org/10.1016/j.freeradbiomed.2015.02.032DOI Listing
July 2015

Quantitating membrane bleb stiffness using AFM force spectroscopy and an optical sideview setup.

Integr Biol (Camb) 2015 Mar 24;7(3):356-63. Epub 2015 Feb 24.

Karlsruhe Institute of Technology (KIT), Center for Functional Nanostructures, Wolfgang-Gaede-Strasse 1a, 76131 Karlsruhe, Germany.

AFM-based force spectroscopy in combination with optical microscopy is a powerful tool for investigating cell mechanics and adhesion on the single cell level. However, standard setups featuring an AFM mounted on an inverted light microscope only provide a bottom view of cell and AFM cantilever but cannot visualize vertical cell shape changes, for instance occurring during motile membrane blebbing. Here, we have integrated a mirror-based sideview system to monitor cell shape changes resulting from motile bleb behavior of Xenopus cranial neural crest (CNC) cells during AFM elasticity and adhesion measurements. Using the sideview setup, we quantitatively investigate mechanical changes associated with bleb formation and compared cell elasticity values recorded during membrane bleb and non-bleb events. Bleb protrusions displayed significantly lower stiffness compared to the non-blebbing membrane in the same cell. Bleb stiffness values were comparable to values obtained from blebbistatin-treated cells, consistent with the absence of a functional actomyosin network in bleb protrusions. Furthermore, we show that membrane blebs forming within the cell-cell contact zone have a detrimental effect on cell-cell adhesion forces, suggesting that mechanical changes associated with bleb protrusions promote cell-cell detachment or prevent adhesion reinforcement. Incorporating a sideview setup into an AFM platform therefore provides a new tool to correlate changes in cell morphology with results from force spectroscopy experiments.
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http://dx.doi.org/10.1039/c4ib00282bDOI Listing
March 2015

Cadherin-11 mediates contact inhibition of locomotion during Xenopus neural crest cell migration.

PLoS One 2013 31;8(12):e85717. Epub 2013 Dec 31.

Zoological Institute, Cell- and Developmental Biology, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.

Collective cell migration is an essential feature both in embryonic development and cancer progression. The molecular mechanisms of these coordinated directional cell movements still need to be elucidated. The migration of cranial neural crest (CNC) cells during embryogenesis is an excellent model for collective cell migration in vivo. These highly motile and multipotent cells migrate directionally on defined routes throughout the embryo. Interestingly, local cell-cell interactions seem to be the key force for directionality. CNC cells can change their migration direction by a repulsive cell response called contact inhibition of locomotion (CIL). Cell protrusions collapse upon homotypic cell-cell contact and internal repolarization leads to formation of new protrusions toward cell-free regions. Wnt/PCP signaling was shown to mediate activation of small RhoGTPase RhoA and inhibition of cell protrusions at the contact side. However, the mechanism how a cell recognizes the contact is poorly understood. Here, we demonstrate that Xenopus cadherin-11 (Xcad-11) mediated cell-cell adhesion is necessary in CIL for directional and collective migration of CNC cells. Reduction of Xcad-11 adhesive function resulted in higher invasiveness of CNC due to loss of CIL. Additionally, transplantation analyses revealed that CNC migratory behaviour in vivo is non-directional and incomplete when Xcad-11 adhesive function is impaired. Blocking Wnt/PCP signaling led to similar results underlining the importance of Xcad-11 in the mechanism of CIL and directional migration of CNC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085717PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877381PMC
August 2014
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