The Effect of Urbanization on the Mycorrhizal Associations and Survival of Three Species of Eastern Hardwoods

Mycorrhizal fungi colonization can be a significant determinant of plant health and establishment success. By protecting roots from pathogens and increasing plant uptake of nutrients and water, mycorrhizal colonization can determine the outcome of competitive interactions between plants, thereby shaping plant community composition. Currently, in remnant forest patches, plants and their fungal symbionts are exposed to varied anthropomorphic effects related to the encroachment of metropolitan areas into rural landscapes. However, little is known about the impact of urbanization on the plant-mycorrhizal fungi association. To assess the effect of urbanization on mycorrhizal fungi root colonization and their role on seedling establishment, we investigated the relationship between mycorrhizal colonization of tree seedlings and seedling survival along an urbanization gradient typical of the mid-western region of the USA. We planted three species of temperate tree seedlings (Acer rubrum, Carya ovata, and Quercus rubra) in each of three landscape types: urban, suburban, and rural forests. We measured the percent of root length of the seedlings colonized by ectomycorrhizal (ECM) and arbuscular mycorrhizal fungi (AMF) and monitored seedling survival during their first growing season. We analyzed the percent root length colonized by mycorrhizae as a function of landscape type (urban-rural) and additional variables known to contribute mycorrhizal colonization (soil phosphorus, soil nitrogen, and initial plant height). We then analyzed seedling survival as a function of the degree of mycorrhizal fungi colonization associated with the landscape gradient and of additional environmental factors (available light and soil moisture). Within a species, we found no changes in levels of mycorrhizal fungi colonization across the urban landscape gradient. Environmental variables (light, soil moisture, soil nutrients) did not significantly vary along the urban gradient, and differences in these variables did not have a measureable effect upon mycorrhizal colonization or survival. Each seedling species had markedly different levels of colonization and responded differently to increasing levels of mycorrhizal colonization. For A. rubrum, survival was independent of mycorrhizal colonization, Q. rubra had a statistically non-significant rise in survival as colonization increased, and C. ovata had a significant positive survival response to more than 60 % colonization. These findings highlight the resilience of mycorrhizal communities across the rural-urban gradient and the potential sensitivity of some species to lower levels of mycorrhizal colonization.Master of ScienceNatural Resources and EnvironmentUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/122695/1/NTONNthesisFull2016.pd

Glucocorticoid (dexamethasone)-induced metabolome changes in healthy males suggest prediction of response and side effects

Glucocorticoids are indispensable anti-inflammatory and decongestant drugs with high prevalence of use at (similar to)0.9% of the adult population. Better holistic insights into glucocorticoid-induced changes are crucial for effective use as concurrent medication and management of adverse effects. The profiles of 214 metabolites from plasma of 20 male healthy volunteers were recorded prior to and after ingestion of a single dose of 4 mg dexamethasone (+20 mg pantoprazole). Samples were drawn at three predefined time points per day: seven untreated (day 1 midday - day 3 midday) and four treated (day 3 evening - day 4 evening) per volunteer. Statistical analysis revealed tremendous impact of dexamethasone on the metabolome with 150 of 214 metabolites being significantly deregulated on at least one time point after treatment (ANOVA, Benjamini-Hochberg corrected, q < 0.05). Inter-person variability was high and remained uninfluenced by treatment. The clearly visible circadian rhythm prior to treatment was almost completely suppressed and deregulated by dexamethasone. The results draw a holistic picture of the severe metabolic deregulation induced by single-dose, short-term glucocorticoid application. The observed metabolic changes suggest a potential for early detection of severe side effects, raising hope for personalized early countermeasures increasing quality of life and reducing health care costs

Baker Center Journal of Applied Public Policy, Vol. III No. I

Welcome to the third issue of the Baker Center Journal for Applied PublicPolicy. I am pleased that this issue, as its predecessors, evidences the vibrancy of the Baker Center’s governance and public policy programs and makes a contribution to our collective understanding about a variety of policy issues currently being discussed in America. Relating to our system of governance, Jess Hale Jr. examines a proposal for a uniform state approach to reining in renegade presidential electors and Professor Glenn Reynolds reviews Jack Goldsmith’s book The Terror Presidency: Law and Judgment Inside the Bush Administration. Relating to media and foreign affairs and the role of the media in political life, Dr. Mike Fitzgerald and two of his students provide us with “A Comparative Study of Images Created by Press Coverage of the United States and the Republic of Belarus.” Relating to health policy, Dr. David Mirvis, recently appointed as a Senior Fellow for Health Policy at the Center, explores the public policy implications of viewing health as an engine of economic growth. Relating to energy and environmental policy, Drs. Bruce Tonn and Amy Gibson and Baker Scholars Stephanie Smith and Rachel Tuck explore U.S. Attitudes and Perspectives on National Energy Policy. I am also very pleased that this issue includes a report of an excellent conference – “Formulation of a Bipartisan Energy and Climate Policy: Toward and Open and Transparent Process “- that was co-sponsored by the Baker Center and the Woodrow Wilson International Center for Scholars. This issue also includes the result ofanother successful collaboration between the Baker and Wilson Centers that focused on “Five Public Policy Ideas for Building Obama’s New Economy.” I look forward to further productive collaborations between the Baker and Wilson Centers. Relating to global security policy, this issue includes a Student Symposium onNational Security. Although the Baker Center Journal has provided an outlet for publication of student scholarship since its inception, I am particularly pleased that the student co-editors - Baker Scholars Elizabeth Wilson Vaughan and Bradford A. Vaughan - took the initiative to expand upon the efforts of their predecessors and to provide us with an expanded set of excellent students essays each of which addresses an important national security policy issue. It is an important part of the Baker Center’s mission to engage UTK students in the political and public policy process, and I applaud our student authors fortheir contributions to this symposium. I hope you find this issue of the Baker Center Journal for Applied Public Policy to be both interesting and thought-provoking and that it will encourage you to participate in America’s unique and wonderful political and policy processes

MEDB-41. Identifying a subgroup of patients with early childhood sonic hedgehog-activated medulloblastoma with unfavorable prognosis after treatment with radiation-sparing regimens including intraventricular methotrexate [Abstract]

PURPOSE/METHODS: Clinical and molecular risk factors in 142 patients 3 years] 47% vs 85% [<1 year] vs 84% [1-3 years], p<0.001). No TP53 mutations were detected (n=47). DNA methylation classification identified three subgroups: SHH-1(v12.3) (n=39), SHH-2(v12.3) (n=19), and SHH-3(v12.3) (n=19), with distinct cytogenetic profiles (chromosome 2 gains in SHH-1(v12.3), very few alterations in SHH-2(v12.3), and chromosome 9q losses in SHH-3(v12.3)), age profiles (median age [years] SHH-1(v12.3): 1.7, SHH-2(v12.3): 0.9, SHH-3(v12.3): 3.0, p<0.001), and histological distribution (SHH-2(v12.3): 74% MBEN, SHH-1(v12.3)/SHH-3(v12.3): 77%/79% DMB, p<0.001). PFS was more unfavorable in patients with SHH-3(v12.3)-medulloblastoma (5-year PFS 53% vs 86% [SHH-1(v12.3)] vs 95% [SHH-2(v12.3)], p=0.002), which remained the only risk factor on multivariable Cox regression for PFS. OS was comparable (5-year OS 94% [SHH-3(v12.3)] vs 97% [SHH-1(v12.3)] vs 100% [SHH-2(v12.3)], p=0.6). 8/9 patients with SHH-3(v12.3)-medulloblastoma received radiotherapy at relapse (6 craniospinal, 2 local [1 Gorlin syndrome, 1 BRCA2 germline mutation], 1 no radiotherapy [Gorlin syndrome]). CONCLUSION: We identify patients with an increased risk of relapse when treated with radiation-sparing approaches among children with early childhood SHH-medulloblastoma. If these tumors differ from SHH-3-medulloblastoma typically described in older children remains to be verified. Treatment recommendations need to consider cancer predisposition syndromes

Inability of granule polarization by NK cells defines tumor resistance and can be overcome by CAR or ADCC mediated targeting

Background: On encountering a susceptible target, natural killer (NK) cells mediate cytotoxicity through highly regulated steps of directed degranulation. Cytotoxic granules converge at the microtubule organizing center and are polarized toward the immunological synapse (IS), followed by granule exocytosis. NK cell retargeting by chimeric antigen receptors (CARs) or mAbs represents a promising strategy for overcoming tumor cell resistance. However, little is known about the lytic granule dynamics of such retargeted NK cells toward NK-cell-resistant tumors. Methods: Here, we used spinning disk confocal microscopy for live-cell imaging to analyze granule-mediated NK cell cytotoxicity in ErbB2-targeted CAR-expressing NK-92 cells (NK-92/5.28.z) and high-affinity FcR transgenic NK-92 cells plus Herceptin toward ErbB2-positive breast cancer cells (MDA-MB-453), which are resistant to parental NK-92. Results: Unmodified NK-92 cells cocultured with resistant cancer cells showed stable conjugate formation and granule clustering, but failed to polarize granules to the IS. In contrast, retargeting by CAR or FcR+Herceptin toward the MDA-MB-453 cells enabled granule polarization to the IS, resulting in highly effective cytotoxicity. We found that in NK-92 the phosphoinositide 3-kinase pathway was activated after contact with resistant MDA-MB-453, while phospholipase C-γ (PLCγ) and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) were not activated. In contrast, retargeting by CAR or antibody-dependent cell-mediated cytotoxicity (ADCC) provided the missing PLCγ and MEK/ERK signals. Conclusions: These observations suggest that NK cells can create conjugates with resistant cancer cells and respond by granule clustering, but the activation signals are insufficient to induce granule polarization and consequent release of lytic enzymes. Retargeting by CAR and/or the FcR/mAb (ADCC) axis provide the necessary signals, leading to granule polarization and thereby overcoming tumor cell resistance

Photopenic defects on O-(2-[F-18]-fluoroethyl)-L-tyrosine PET: clinical relevance in glioma patients

Background. O-(2-[F-18]-fluoroethyl)-L-tyrosine (FET) PET has a sensitivity of more than 90% to detect gliomas. In the remaining small fraction of gliomas without increased tracer uptake, some tumors even show photopenic defects whose clinical significance is unclear. Methods. Glioma patients with a negative FET PET scan prior to neuropathological confirmation were identified retrospectively. Gliomas were rated visually as (i) having indifferent FET uptake or (ii) photopenic, if FET uptake was below background activity. FET uptake in the area of signal hyperintensity on the T2/fluid attenuated inversion recovery-weighted MRI was evaluated by mean standardized uptake value (SUV) and mean tumor-to-brain ratio (TBR). The progression-free survival (PFS) of photopenic gliomas was compared with that of gliomas with indifferent FET uptake. Results. Of 100 FET-negative gliomas, 40 cases with photopenic defects were identified. Fifteen of these 40 cases (38%) had World Health Organization (WHO) grades III and IV gliomas. FET uptake in photopenic gliomas was significantly decreased compared with both the healthy-appearing brain tissue (SUV, 0.89 +/- 0.26 vs 1.08 +/- 0.23; P < 0.001) and gliomas with indifferent FET uptake (TBR, 0.82 +/- 0.09 vs 0.96 +/- 0.13; P < 0.001). Irrespective of the applied treatment, isocitrate dehydrogenase (IDH)-mutated WHO grade II diffuse astrocytoma patients with indifferent FET uptake (n = 25) had a significantly longer PFS than patients with IDH-mutated diffuse astrocytomas (WHO grade II) with photopenic defects (n = 11) (51 vs 24 mo; P = 0.027). The multivariate survival analysis indicated that photopenic defects predict an unfavorable PFS (P = 0.009). Conclusion. Photopenic gliomas in negative FET PET scans should be managed more actively, as they seem to have a higher risk of harboring a higher-grade glioma and an unfavorable outcome