908 research outputs found

    Anthropogenic Litter Abundance and Composition in Urban Streams: Influence of Site and Habitat

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    Anthropogenic litter (AL; trash including plastic and other materials) is a global ecological concern. Rivers move AL from land to oceans, but the distribution of AL within rivers is less often studied. We examined the abundance and composition of AL in different habitats at multiple sites in an urban river. We expect sorting of AL based on density, and that sites with greater urban land use will have the most AL. These data will be helpful to improve AL mitigation and removal strategies

    Mental Health Status and Perceived Barriers to Seeking Treatment in Rural Reserve Component Veterans

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    National Guard and Reserve (RC) troops (N=617) primarily from the Appalachian Region in Southwestern Pennsylvania who recently returned from deployment in support of current military conflicts responded to a survey that assessed their demographics, mental health symptoms, help-seeking behaviors, barriers for not seeking treatment, deployment history, and stressors. Veterans were classified as rural (N = 334) or non-rural (N = 283). Rural participants reported a significantly greater number of issues with transportation/access in seeking mental health treatment, were more likely to perceive others as worse off as a reason not to seek treatment, had a more negative attitude toward seeking treatment for mental health problems, and reported fewer concerns about a mental health problem affecting their career. Recommendations for mental health care providers and policymakers are offered based on the results, including the importance of recognizing the distinctive barriers to care that RC Appalachian veterans face when they come back into civilian communities, many of them rural

    Rescue of Degradation-Prone Mutants of the FK506-Rapamycin Binding (FRB) Protein with Chemical Ligands

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    We recently reported that certain mutations in the FK506-rapamycin binding (FRB) domain disrupt its stability in vitro and in vivo (Stankunas et al. Mol. Cell , 2003 , 12 , 1615). To determine the precise residues that cause instability, we calculated the folding free energy (Δ G ) of a collection of FRB mutants by measuring their intrinsic tryptophan fluorescence during reversible chaotropic denaturation. Our results implicate the T2098L point mutation as a key determinant of instability. Further, we found that some of the mutants in this collection were destabilised by up to 6 kcal mol −1 relative to the wild type. To investigate how these mutants behave in cells, we expressed firefly luciferase fused to FRB mutants in African green monkey kidney (COS) cell lines and mouse embryonic fibroblasts (MEFs). When unstable FRB mutants were used, we found that the protein levels and the luminescence intensities were low. However, addition of a chemical ligand for FRB, rapamycin, restored luciferase activity. Interestingly, we found a roughly linear relationship between the Δ G of the FRB mutants calculated in vitro and the relative chemical rescue in cells. Because rapamycin is capable of simultaneously binding both FRB and the chaperone, FK506-binding protein (FKBP), we next examined whether FKBP might contribute to the protection of FRB mutants. Using both in vitro experiments and a cell-based model, we found that FKBP stabilizes the mutants. These findings are consistent with recent models that suggest damage to intrinsic Δ G can be corrected by pharmacological chaperones. Further, these results provide a collection of conditionally stable fusion partners for use in controlling protein stability.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56088/1/1162_ftp.pd

    Novel substrates as sources of ancient DNA: : prospects and hurdles

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    Following the discovery in the late 1980s that hard tissues such as bones and teeth preserve genetic information, the field of ancient DNA analysis has typically concentrated upon these substrates. The onset of high-throughput sequencing, combined with optimized DNA recovery methods, has enabled the analysis of a myriad of ancient species and specimens worldwide, dating back to the Middle Pleistocene. Despite the growing sophistication of analytical techniques, the genetic analysis of substrates other than bone and dentine remain comparatively “novel”. Here, we review analyses of other biological substrates which offer great potential for elucidating phylogenetic relationships, paleoenvironments, and microbial ecosystems including (1) archaeological artifacts and ecofacts; (2) calcified and/or mineralized biological deposits; and (3) biological and cultural archives. We conclude that there is a pressing need for more refined models of DNA preservation and bespoke tools for DNA extraction and analysis to authenticate and maximize the utility of the data obtained. With such tools in place the potential for neglected or underexploited substrates to provide a unique insight into phylogenetics, microbial evolution and evolutionary processes will be realized

    Isolation and culture of murine bone marrow-derived macrophages for nitric oxide and redox biology

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    Macrophages are mononuclear phagocytes derived from haematopoietic progenitors that are widely distributed throughout the body. These cells participate in both innate and adaptive immune responses and lie central to the processes of inflammation, development, and homeostasis. Macrophage physiology varies depending on the environment in which they reside and they exhibit rapid functional adaption in response to external stimuli. To study macrophages in vitro, cells are typically cultured ex vivo from the peritoneum or alveoli, or differentiated from myeloid bone marrow progenitor cells to form bone marrow-derived macrophages (BMDMs). BMDMs represent an efficient and cost-effective means of studying macrophage biology. However, the inherent sensitivity of macrophages to biochemical stimuli (such as cytokines, metabolic intermediates, and RNS/ROS) makes it imperative to control experimental conditions rigorously. Therefore, the aim of this study was to establish an optimised and standardised method for the isolation and culture of BMDMs. We used classically activated macrophages isolated from WT and nitric oxide (NO)-deficient mice to develop a standardised culture method, whereby the constituents of the culture media are defined. We then methodically compared our standardised protocol to the most commonly used method of BMDM culture to establish an optimal protocol for the study of nitric oxide (NO)-redox biology and immunometabolism in vitro. [Abstract copyright: Copyright © 2020. Published by Elsevier Inc.

    Continuity in the face of a slowly unfolding catastrophe : the persistence of Icelandic settlement despite large-scale soil erosion

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    The National Science Foundation of America provided financial support for this research through grants 1202692 ‘Comparative Island Ecodynamics in the North Atlantic’, and 1249313 ‘Tephra layers and early warning signals for critical transitions’.Soil erosion in Iceland since people first settled the island about 1,100 years ago has fundamentally changed some 15-30% of the island’s total surface area. This provides a unique case to evaluate the consequences of a slowly unfolding environmental catastrophe that has affected, and is continuing to affect a primary means of subsistence for a whole society. Buffered by the sufferings of regions of Iceland, individual farms and particular social groups, Icelandic society as a whole has endured through subsistence flexibility, social inequalities, and the ability to tap into larger provisioning and economic networks. This demonstrates how an adaptable people can confront challenges through social organisation and by diversifying their impacts ecosystems. In the medium term—multi-century timescales—this can be an effective, if costly, strategy, in terms of both the environment and society. Soil conservation is now a national priority, woodland is returning, and climate warming is opening up more potentials for Icelandic arable agriculture. However, the slow catastrophe of Icelandic soil erosion is still unfolding, with the perspective of the longue durĂ©e it is evident that decisions made in the Viking Age and medieval period still resonate, constraining future options for resilience and adaptive flexibility.Postprin

    Cardiomyocyte tetrahydrobiopterin synthesis regulates fatty acid metabolism and susceptibility to ischaemia-reperfusion injury

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    New Findings What is the central question of this study? What are the physiological roles of cardiomyocyte-derived tetrahydrobiopterin (BH4) in cardiac metabolism and stress response? What is the main finding and its importance? Cardiomyocyte BH4 has a physiological role in cardiac metabolism. There was a shift of substrate preference from fatty acid to glucose in hearts with targeted deletion of BH4 synthesis. The changes in fatty-acid metabolic profile were associated with a protective effect in response to ischaemia–reperfusion (IR) injury, and reduced infarct size. Manipulating fatty acid metabolism via BH4 availability could play a therapeutic role in limiting IR injury. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthases in which its production of NO is crucial for cardiac function. However, non-canonical roles of BH4 have been discovered recently and the cell-specific role of cardiomyocyte BH4 in cardiac function and metabolism remains to be elucidated. Therefore, we developed a novel mouse model of cardiomyocyte BH4 deficiency, by cardiomyocyte-specific deletion of Gch1, which encodes guanosine triphosphate cyclohydrolase I, a required enzyme for de novo BH4 synthesis. Cardiomyocyte (cm)Gch1 mRNA expression and BH4 levels from cmGch1 KO mice were significantly reduced compared to Gch1flox/flox (WT) littermates. Transcriptomic analyses and protein assays revealed downregulation of genes involved in fatty acid oxidation in cmGch1 KO hearts compared with WT, accompanied by increased triacylglycerol concentration within the myocardium. Deletion of cardiomyocyte BH4 did not alter basal cardiac function. However, the recovery of left ventricle function was improved in cmGch1 KO hearts when subjected to ex vivo ischaemia–reperfusion (IR) injury, with reduced infarct size compared to WT hearts. Metabolomic analyses of cardiac tissue after IR revealed that long-chain fatty acids were increased in cmGch1 KO hearts compared to WT, whereas at 5 min reperfusion (post-35 min ischaemia) fatty acid metabolite levels were higher in WT compared to cmGch1 KO hearts. These results indicate a new role for BH4 in cardiomyocyte fatty acid metabolism, such that reduction of cardiomyocyte BH4 confers a protective effect in response to cardiac IR injury. Manipulating cardiac metabolism via BH4 could play a therapeutic role in limiting IR injury

    Acute Effects of JUUL and IQOS in Cigarette Smokers

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    BACKGROUND: JUUL is an electronic cigarette that aerosolizes a nicotine-containing liquid, while IQOS heats tobacco to produce an aerosol. Both are marketed to smokers, but their effects have seldom been examined in this population. METHODS: Eighteen cigarette smokers (13 men) with no JUUL or IQOS experience completed a within-subject, laboratory study assessing nicotine delivery and subjective effects after controlled (10 puffs, ~30 sec interpuff interval) and ad libitum (90 min) use of JUUL, IQOS, or own-brand cigarettes (OB). RESULTS: JUUL increased mean plasma nicotine concentration significantly from 2.2 (SD=0.7) ng/ml to 9.8 (4.9) ng/mL after 10 puffs and to 11.5 (9.3) ng/mL after ad libitum use. IQOS increased mean plasma nicotine significantly from 2.1 (0.2) ng/mL to 12.7 (6.2) ng/mL after 10 puffs and to 11.3 (8.0) ng/mL after ad libitum use. OB increased mean plasma nicotine significantly from 2.1 (0.2) ng/mL to 20.4 (11.4) ng/mL after 10 puffs and to 21.0 (10.2) ng/mL after ad libitum use. Mean OB plasma nicotine concentration was significantly higher than JUUL and IQOS. OB increased expired CO concentration, but IQOS and JUUL did not. “Craving a cigarette/nicotine” and “Urges to smoke” were reduced significantly for all products following the directed bout. CONCLUSIONS: Among smokers, JUUL and IQOS delivered less nicotine than cigarettes. Also, in this sample, IQOS and OB reduced abstinence symptoms more effectively than JUUL. Additional work with experienced JUUL and IQOS users is needed, as their nicotine delivery profiles and subjective experiences may differ

    The interindividual variation in femoral neck width is associated with the acquisition of predictable sets of morphological and tissue‐quality traits and differential bone loss patterns

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    A better understanding of femoral neck structure and age‐related bone loss will benefit research aimed at reducing fracture risk. We used the natural variation in robustness (bone width relative to length) to analyze how adaptive processes covary traits in association with robustness, and whether the variation in robustness affects age‐related bone loss patterns. Femoral necks from 49 female cadavers (29–93 years of age) were evaluated for morphological and tissue‐level traits using radiography, peripheral quantitative computed tomography, micro–computed tomography, and ash‐content analysis. Femoral neck robustness was normally distributed and varied widely with a coefficient of variation of 14.9%. Age‐adjusted partial regression analysis revealed significant negative correlations ( p   0.2). The results indicated that slender femora were constructed with a different set of traits compared to robust femora, and that the natural variation in robustness was a determinant of age‐related bone loss patterns. Clinical diagnoses and treatments may benefit from a better understanding of these robustness‐specific structural and aging patterns. © 2012 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92024/1/1614_ftp.pd
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