1,214 research outputs found
Groundwater residence time estimates obscured by anthropogenic carbonate
© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Seltzer, A. M., Bekaert, D. V., Barry, P. H., Durkin, K. E., Mace, E. K., Aalseth, C. E., Zappala, J. C., Mueller, P., Jurgens, B., & Kulongoski, J. T. Groundwater residence time estimates obscured by anthropogenic carbonate. Science Advances, 7(17), (2021): eabf3503, https://doi.org/10.1126/sciadv.abf3503.Groundwater is an important source of drinking and irrigation water. Dating groundwater informs its vulnerability to contamination and aids in calibrating flow models. Here, we report measurements of multiple age tracers (14C, 3H, 39Ar, and 85Kr) and parameters relevant to dissolved inorganic carbon (DIC) from 17 wells in California’s San Joaquin Valley (SJV), an agricultural region that is heavily reliant on groundwater. We find evidence for a major mid-20th century shift in groundwater DIC input from mostly closed- to mostly open-system carbonate dissolution, which we suggest is driven by input of anthropogenic carbonate soil amendments. Crucially, enhanced open-system dissolution, in which DIC equilibrates with soil CO2, fundamentally affects the initial 14C activity of recently recharged groundwater. Conventional 14C dating of deeper SJV groundwater, assuming an open system, substantially overestimates residence time and thereby underestimates susceptibility to modern contamination. Because carbonate soil amendments are ubiquitous, other groundwater-reliant agricultural regions may be similarly affected.his work was conducted as a part of the USGS National Water Quality Assessment Program (NAWQA) Enhanced Trends Project (https://water.usgs.gov/nawqa/studies/gwtrends/). Measurements at Argonne National Laboratory were supported by Department of Energy, Office of Science under contract DE-AC02-06CH11357. Measurements at Pacific Northwest National Laboratory were part of the Ultra-Sensitive Nuclear Measurements Initiative conducted under the Laboratory Directed Research and Development Program. PNNL is operated by Battelle for the U.S. Department of Energy under Contract DE-AC05-76RL01830. This work was also partially supported by NSF award OCE-1923915 (to A.M.S. and P.H.B. at WHOI)
High-Throughput Analysis of Lung Immune Cells in a Combined Murine Model of Agriculture Dust-Triggered Airway Inflammation With Rheumatoid Arthritis
Rheumatoid arthritis (RA)-associated lung disease is a leading cause of mortality in RA, yet the mechanisms linking lung disease and RA remain unknown. Using an established murine model of RA-associated lung disease combining collagen-induced arthritis (CIA) with organic dust extract (ODE)-induced airway inflammation, differences among lung immune cell populations were analyzed by single cell RNA-sequencing. Additionally, four lung myeloid-derived immune cell populations including macrophages, monocytes/macrophages, monocytes, and neutrophils were isolated by fluorescence cell sorting and gene expression was determined by NanoString analysis. Unsupervised clustering revealed 14 discrete clusters among Sham, CIA, ODE, and CIA+ODE treatment groups: 3 neutrophils (inflammatory, resident/transitional, autoreactive/suppressor), 5 macrophages (airspace, differentiating/recruited, recruited, resident/interstitial, and proliferative airspace), 2 T-cells (differentiating and effector), and a single cluster each of inflammatory monocytes, dendritic cells, B-cells and natural killer cells. Inflammatory monocytes, autoreactive/suppressor neutrophils, and recruited/differentiating macrophages were predominant with arthritis induction (CIA and CIA+ODE). By specific lung cell isolation, several interferon-related and autoimmune genes were disproportionately expressed among CIA and CIA+ODE (e.g. Oasl1, Oas2, Ifit3, Gbp2, Ifi44, and Zbp1), corresponding to RA and RA-associated lung disease. Monocytic myeloid-derived suppressor cells were reduced, while complement genes (e.g. C1s1 and Cfb) were uniquely increased in CIA+ODE mice across cell populations. Recruited and inflammatory macrophages/monocytes and neutrophils expressing interferon-, autoimmune-, and complement-related genes might contribute towards pro-fibrotic inflammatory lung responses following airborne biohazard exposures in setting of autoimmune arthritis and could be predictive and/or targeted to reduce disease burden
The genome sequence of <i>Trypanosoma brucei gambiense</i>, causative agent of chronic Human African Trypanosomiasis
<p><b>Background:</b> <i>Trypanosoma brucei gambiense</i> is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness, a disease endemic across often poor and rural areas of Western and Central Africa. We have previously published the genome sequence of a <i>T. b. brucei</i> isolate, and have now employed a comparative genomics approach to understand the scale of genomic variation between <i>T. b. gambiense</i> and the reference genome. We sought to identify features that were uniquely associated with <i>T. b. gambiense</i> and its ability to infect humans.</p>
<p><b>Methods and findings:</b> An improved high-quality draft genome sequence for the group 1 <i>T. b. gambiense</i> DAL 972 isolate was produced using a whole-genome shotgun strategy. Comparison with <i>T. b. brucei</i> showed that sequence identity averages 99.2% in coding regions, and gene order is largely collinear. However, variation associated with segmental duplications and tandem gene arrays suggests some reduction of functional repertoire in <i>T. b. gambiense</i> DAL 972. A comparison of the variant surface glycoproteins (VSG) in <i>T. b. brucei</i> with all <i>T. b. gambiense</i> sequence reads showed that the essential structural repertoire of VSG domains is conserved across <i>T. brucei</i>.</p>
<p><b>Conclusions:</b> This study provides the first estimate of intraspecific genomic variation within <i>T. brucei</i>, and so has important consequences for future population genomics studies. We have shown that the <i>T. b. gambiense</i> genome corresponds closely with the reference, which should therefore be an effective scaffold for any <i>T. brucei</i> genome sequence data. As VSG repertoire is also well conserved, it may be feasible to describe the total diversity of variant antigens. While we describe several as yet uncharacterized gene families with predicted cell surface roles that were expanded in number in <i>T. b. brucei</i>, no <i>T. b. gambiense</i>-specific gene was identified outside of the subtelomeres that could explain the ability to infect humans.</p>
Epidemiology, prehospital care and outcomes of patients arriving by ambulance with dyspnoea: An observational study
Background: This study aimed to determine epidemiology and outcome for patients presenting to emergency departments (ED) with shortness of breath who were transported by ambulance. Methods: This was a planned sub-study of a prospective, interrupted time series cohort study conducted at three time points in 2014 and which included consecutive adult patients presenting to the ED with dyspnoea as a main symptom. For this sub-study, additional inclusion criteria were presentation to an ED in Australia or New Zealand and transport by ambulance. The primary outcomes of interest are the epidemiology and outcome of these patients. Analysis was by descriptive statistics and comparisons of proportions. Results: One thousand seven patients met inclusion criteria. Median age was 74 years (IQR 61-68) and 46.1 % were male. There was a high rate of co-morbidity and chronic medication use. The most common ED diagnoses were lower respiratory tract infection (including pneumonia, 22.7 %), cardiac failure (20.5%) and exacerbation of chronic obstructive pulmonary disease (19.7 %). ED disposition was hospital admission (including ICU) for 76.4 %, ICU admission for 5.6 % and death in ED in 0.9 %. Overall in-hospital mortality among admitted patients was 6.5 %. Discussion: Patients transported by ambulance with shortness of breath make up a significant proportion of ambulance caseload and have high comorbidity and high hospital admission rate. In this study, >60 % were accounted for by patients with heart failure, lower respiratory tract infection or COPD, but there were a wide range of diagnoses. This has implications for service planning, models of care and paramedic training. Conclusion: This study shows that patients transported to hospital by ambulance with shortness of breath are a complex and seriously ill group with a broad range of diagnoses. Understanding the characteristics of these patients, the range of diagnoses and their outcome can help inform training and planning of services
Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site.
Coenzyme A (CoA) is a fundamental co-factor for all life, involved in numerous metabolic pathways and cellular processes, and its biosynthetic pathway has raised substantial interest as a drug target against multiple pathogens including Mycobacterium tuberculosis. The biosynthesis of CoA is performed in five steps, with the second and third steps being catalysed in the vast majority of prokaryotes, including M. tuberculosis, by a single bifunctional protein, CoaBC. Depletion of CoaBC was found to be bactericidal in M. tuberculosis. Here we report the first structure of a full-length CoaBC, from the model organism Mycobacterium smegmatis, describe how it is organised as a dodecamer and regulated by CoA thioesters. A high-throughput biochemical screen focusing on CoaB identified two inhibitors with different chemical scaffolds. Hit expansion led to the discovery of potent and selective inhibitors of M. tuberculosis CoaB, which we show to bind to a cryptic allosteric site within CoaB
Physicochemical Characterization, and Relaxometry Studies of Micro-Graphite Oxide, Graphene Nanoplatelets, and Nanoribbons
The chemistry of high-performance magnetic resonance imaging contrast agents remains an active area of research. In this work, we demonstrate that the potassium permanganate-based oxidative chemical procedures used to synthesize graphite oxide or graphene nanoparticles leads to the confinement (intercalation) of trace amounts of Mn2+ ions between the graphene sheets, and that these manganese intercalated graphitic and graphene structures show disparate structural, chemical and magnetic properties, and high relaxivity (up to 2 order) and distinctly different nuclear magnetic resonance dispersion profiles compared to paramagnetic chelate compounds. The results taken together with other published reports on confinement of paramagnetic metal ions within single-walled carbon nanotubes (a rolled up graphene sheet) show that confinement (encapsulation or intercalation) of paramagnetic metal ions within graphene sheets, and not the size, shape or architecture of the graphitic carbon particles is the key determinant for increasing relaxivity, and thus, identifies nano confinement of paramagnetic ions as novel general strategy to develop paramagnetic metal-ion graphitic-carbon complexes as high relaxivity MRI contrast agents
Performance of Al-Mn Transition-Edge Sensor Bolometers in SPT-3G
SPT-3G is a polarization-sensitive receiver, installed on the South Pole
Telescope, that measures the anisotropy of the cosmic microwave background
(CMB) from degree to arcminute scales. The receiver consists of ten
150~mm-diameter detector wafers, containing a total of 16,000 transition-edge
sensor (TES) bolometers observing at 95, 150, and 220 GHz. During the 2018-2019
austral summer, one of these detector wafers was replaced by a new wafer
fabricated with Al-Mn TESs instead of the Ti/Au design originally deployed for
SPT-3G. We present the results of in-lab characterization and on-sky
performance of this Al-Mn wafer, including electrical and thermal properties,
optical efficiency measurements, and noise-equivalent temperature. In addition,
we discuss and account for several calibration-related systematic errors that
affect measurements made using frequency-domain multiplexing readout
electronics.Comment: 9 pages, 5 figures, submitted to the Journal of Low Temperature
Physics: LTD18 Special Editio
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