New approaches to investigating the function of mycelial networks

Fungi play a key role in ecosystem nutrient cycles by scavenging, concentrating, translocating and redistributing nitrogen. To quantify and predict fungal nitrogen redistribution, and assess the importance of the integrity of fungal networks in soil for ecosystem function, we need better understanding of the structures and processes involved. Until recently nitrogen translocation has been experimentally intractable owing to the lack of a suitable radioisotope tracer for nitrogen, and the impossibility of observing nitrogen translocation in real time under realistic conditions. We have developed an imaging method for recording the magnitude and direction of amino acid flow through the whole mycelial network as it captures, assimilates and channels its carbon and nitrogen resources, while growing in realistically heterogeneous soil microcosms. Computer analysis and modeling, based on these digitized video records, can reveal patterns in transport that suggest experimentally testable hypotheses. Experimental approaches that we are developing include genomics and stable isotope NMR to investigate where in the system nitrogen compounds are being acquired and stored, and where they are mobilized for transport or broken down. The results are elucidating the interplay between environment, metabolism, and the development and function of transport networks as mycelium forages in soil. The highly adapted and selected foraging networks of fungi may illuminate fundamental principles applicable to other supply networks

Effect of Chemotherapy on the Microbiota and Metabolome of Human Milk: A Case Report

BACKGROUND: Human milk is an important source of bacteria for the developing infant and has been shown to influence the bacterial composition of the neonatal gut, which in turn can affect disease risk later in life. Human milk is also an important source of nutrients, influencing bacterial composition but also directly affecting the host. While recent studies have emphasized the adverse effects of antibiotic therapy on the infant microbiota, the effects of maternal chemotherapy have not been previously studied. Here we report the effects of drug administration on the microbiota and metabolome of human milk. METHODS: Mature milk was collected every two weeks over a four month period from a lactating woman undergoing chemotherapy for Hodgkin\u27s lymphoma. Mature milk was also collected from healthy lactating women for comparison. Microbial profiles were analyzed by 16S sequencing and the metabolome by gas chromatography-mass spectrometry. FINDINGS: Chemotherapy caused a significant deviation from a healthy microbial and metabolomic profile, with depletion of genera Bifidobacterium, Eubacterium, Staphylococcus and Cloacibacterium in favor of Acinetobacter, Xanthomonadaceae and Stenotrophomonas. The metabolites docosahexaenoic acid and inositol known for their beneficial effects were also decreased. CONCLUSION: With milk contents being critical for shaping infant immunity and development, consideration needs to be given to the impact of drugs administered to the mother and the long-term potential consequences for the health of the infant

Disseminated tuberculosis among hospitalised HIV patients in South Africa: a common condition that can be rapidly diagnosed using urine-based assays.

HIV-associated disseminated TB (tuberculosis) has been under-recognised and poorly characterised. Blood culture is the gold-standard diagnostic test, but is expensive, slow, and may under-diagnose TB dissemination. In a cohort of hospitalised HIV patients, we aimed to report the prevalence of TB-blood-culture positivity, performance of rapid diagnostics as diagnostic surrogates, and better characterise the clinical phenotype of disseminated TB. HIV-inpatients were systematically investigated using sputum, urine and blood testing. Overall, 132/410 (32.2%) patients had confirmed TB; 41/132 (31.1%) had a positive TB blood culture, of these 9/41 (22.0%) died within 90-days. In contrast to sputum diagnostics, urine Xpert and urine-lipoarabinomannan (LAM) combined identified 88% of TB blood-culture-positive patients, including 9/9 who died within 90-days. For confirmed-TB patients, half the variation in major clinical variables was captured on two principle components (PCs). Urine Xpert, urine LAM and TB-blood-culture positive patients clustered similarly on these axes, distinctly from patients with localised disease. Total number of positive tests from urine Xpert, urine LAM and MTB-blood-culture correlated with PCs (p < 0.001 for both). PC1&PC2 independently predicted 90-day mortality (ORs 2.6, 95%CI = 1.3-6.4; and 2.4, 95%CI = 1.3-4.5, respectively). Rather than being a non-specific diagnosis, disseminated TB is a distinct, life-threatening condition, which can be diagnosed using rapid urine-based tests, and warrants specific interventional trials

Immobilization of cadmium and lead by Lactobacillus rhamnosus GR-1 mitigates apical-to-basolateral heavy metal translocation in a Caco-2 model of the intestinal epithelium

© 2018, © 2018 The Author(s). Published by Taylor & Francis. Heavy metals are highly toxic elements that contaminate the global food supply and affect human and wildlife health. Purification technologies are often too expensive or not practically applicable for large-scale implementation, especially in impoverished nations where heavy metal contamination is widespread. Lactobacillus rhamnosus GR-1 (LGR-1) was shown in previous work to reduce heavy metal bioaccumulation in a Tanzanian cohort of women and children through indeterminant mechanisms. Here, it was hypothesized that LGR-1 could sequester the heavy metals lead (Pb) and cadmium (Cd), thereby reducing their absorption across intestinal epithelium. LGR-1 and other lactobacilli significantly reduced the amount of Pb and Cd in solution at all concentrations tested (0.5 mg/L–50 mg/L) and exhibited sustained binding profiles over a 48-hour period. Relative binding efficiency of LGR-1 decreased as Pb concentration increased, with an absolute minimum binding threshold apparent at concentrations of 2 mg/L and above. Electron microscopy revealed that Pb formed irregular cell-surface clusters on LGR-1, while Cd appeared to form intracellular polymeric clusters. Additionally, LGR-1 was able to significantly reduce apical-to-basolateral translocation of Pb and Cd in a Caco-2 model of the intestinal epithelium. These findings demonstrate the absorbent properties of LGR-1 can immobilize Pb and Cd, effectively reducing their translocation across the intestinal epithelium in vitro. Oral administration of heavy metal-binding Lactobacillus spp. (many of which are known human symbionts and strains of established probiotics) may offer a simple and effective means to reduce the amount of heavy metals absorbed from foods in contaminated regions of the world

Rapid radiocarbon (14C) analysis of coral and carbonate samples using a continuous-flow accelerator mass spectrometry (CFAMS) system

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 26 (2011): PA4212, doi:10.1029/2011PA002174.Radiocarbon analyses of carbonate materials provide critical information for understanding the last glacial cycle, recent climate history and paleoceanography. Methods that reduce the time and cost of radiocarbon (14C) analysis are highly desirable for large sample sets and reconnaissance type studies. We have developed a method for rapid radiocarbon analysis of carbonates using a novel continuous-flow accelerator mass spectrometry (CFAMS) system. We analyzed a suite of deep-sea coral samples and compared the results with those obtained using a conventional AMS system. Measurement uncertainty is <0.02 Fm or 160 Ryr for a modern sample and the mean background was 37,800 Ryr. Radiocarbon values were repeatable and in good agreement with those from the conventional AMS system. Sample handling and preparation is relatively simple and the method offered a significant increase in speed and cost effectiveness. We applied the method to coral samples from the Eastern Pacific Ocean to obtain an age distribution and identify samples for further analysis. This paper is intended to update the paleoceanographic community on the status of this new method and demonstrate its feasibility as a choice for rapid and affordable radiocarbon analysis.This work was performed under NSF Cooperative Agreement OCE‐0753487, and also NSF‐OPP awards 0636787 and 0944474

Diagnostic accuracy, incremental yield and prognostic value of Determine TB-LAM for routine diagnostic testing for tuberculosis in HIV-infected patients requiring acute hospital admission in South Africa: a prospective cohort

Abstract Background We previously reported that one-third of HIV-positive adults requiring medical admission to a South African district hospital had laboratory-confirmed tuberculosis (TB) and that almost two-thirds of cases could be rapidly diagnosed using Xpert MTB/RIF-testing of concentrated urine samples obtained on the first day of admission. Implementation of urine-based, routine, point-of-care TB screening is an attractive intervention that might be facilitated by use of a simple, low-cost diagnostic tool, such as the Determine TB-LAM lateral-flow rapid test for HIV-associated TB. Methods Sputum, urine and blood samples were systematically obtained from unselected HIV-positive adults within 24 hours of admission to a South African township hospital. Additional clinical samples were obtained during hospitalization as clinically indicated. TB was defined by the detection of Mycobacterium tuberculosis in any sample using Xpert MTB/RIF or liquid culture. The diagnostic yield, accuracy and prognostic value of urine-lipoarabinomannan (LAM) testing were determined, but urine-LAM results did not inform treatment decisions. Results Consecutive HIV-positive adult acute medical admissions not already receiving TB treatment (n = 427) were enrolled regardless of clinical presentation or symptoms. TB was diagnosed in 139 patients (TB prevalence 32.6%; median CD4 count 80 cells/μL). In the first 24 hours of admission, sputum (spot and/or induced) samples were obtained from 37.0% of patients and urine samples from 99.5% of patients (P < 0.001). The diagnostic yields from these specimens were 19.4% (n = 27/139) for sputum-microscopy, 26.6% (n = 37/139) for sputum-Xpert, 38.1% (n = 53/139) for urine-LAM and 52.5% (n = 73/139) for sputum-Xpert/urine-LAM combined (P < 0.01). Corresponding yields among patients with CD4 counts <100 cells/μL were 18.9%, 24.3%, 55.4% and 63.5%, respectively (P < 0.01). The diagnostic yield of urine-LAM was unrelated to respiratory symptoms, and LAM assay specificity (using a grade-2 cut-off) was 98.9% (274/277; 95% confidence interval [CI] 96.9–99.8). Among TB cases, positive urine-LAM status was strongly associated with mortality at 90 days (adjusted hazard ratio 4.20; 95% CI 1.50–11.75). Conclusions Routine testing for TB in newly admitted HIV-positive adults using Determine TB-LAM to test urine provides major incremental diagnostic yield with very high specificity when used in combination with sputum testing and has important utility among those without respiratory TB symptoms and/or unable to produce sputum. The assay also rapidly identifies individuals with a poor prognosis

A phase II study of paclitaxel for the treatment of ovarian stromal tumors: An NRG Oncology/ Gynecologic Oncology Group Study

To estimate the probability of complete clinical response and toxicity of paclitaxel as second-line chemotherapy in measurable disease patients with malignant tumors of the ovarian stroma, and to evaluate the value of inhibin for predicting response

Impact of Controlling the Site Distribution of Al Atoms on Catalytic Properties in Ferrierite-Type Zeolites

Zeolites with the ferrierite (FER) topology are synthesized using a combination of tetramethylammonium (TMA) cations with differently sized cyclic amines (pyrrolidine (Pyr), hexamethyleneimine (HMI), and 1,4- diazabicyclo[2.2.2]octane (DAB)). Using these organic structure-directing agents (SDAs), low Si/Al ratios and concentrated synthesis mixtures favor the crystallization of FER materials. Increasing the size of the cyclic amine or decreasing the aluminum content leads to the crystallization of other phases or the creation of excessive amounts of connectivity defects. TMA cations play a decisive role in the synthesis of the FER materials, and their presence allows the use of HMI to synthesize FER. Proton MAS NMR is used to quantify the accessibility of pyridine to acid sites in these FER samples, where it is found that the FER + HMI + TMA sample contains only 27% acid sites in the 8-MR channels, whereas FER + Pyr and FER + Pyr + TMA contain 89% and 84%, respectively. The constraint index (CI) test and the carbonylation of dimethyl ether (DME) with carbon monoxide are used as probe reactions to evaluate how changes in the aluminum distribution in these FER samples affect their catalytic behavior. Results show that the use of Pyr as an SDA results in the selective population of acid sites in the 8-MR channels, whereas the use of HMI generates FER zeolites with an increased concentration of acid sites in the 10-MR channels

Design and reality : continuous-flow accelerator mass spectrometry (CFAMS)

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 269 (2011): 3176–3179, doi:10.1016/j.nimb.2011.04.019.In 2007 we published the design of a novel accelerator mass spectrometry (AMS) system capable of analyzing gaseous samples injected continuously into a microwave plasma gas ion source. Obvious advantages of such a system are drastically reduced processing times and avoidance of potentially contaminating chemical preparation steps. Another paper in these proceedings will present the progress with the development of the microwave gas ion source that has since been built and tested at the National Ocean Sciences AMS Facility in Woods Hole. In this paper we will review the original design and present updates, reflecting our recent encouraging experience with the system. A simple summary: large acceptance ion beam optics design is beneficial to accelerator mass spectrometry in general, but essential to AMS with plasma gas ion sources