Biotic and abiotic factors contributing to the invasion success of microstegium vimineum in eastern deciduous forests.

Forest managers face multiple challenges in maintaining woodland systems, including climate change, habitat destruction and fragmentation, and the invasion of novel species. Invaders can change microclimates, alter nutrient cycling and understory habitat, and outcompete native species, leading to native species population declines and reduction in species richness. To effectively combat plant invasions it is necessary to first understand factors contributing to invasive species spread, including the complex interactions between invaders and native biota. This dissertation investigates the abiotic conditions and biotic interactions associated with invasion success of the non-native grass Microstegium vimineum, which is a species of great concern for forest managers throughout the eastern US. My initial study identified the most important abiotic elements associated with Microstegium presence. I found light availability and soil moisture to be the strongest predictors of Microstegium cover, followed by soil nitrogen and soil phosphorous. In this study I also examined the relationship between Microstegium and soil arbuscular mycorrhizae. I found no differences in abundance of soil mycorrhizae between invaded and noninvaded areas, and no difference in root colonization of Microstegium across abiotic gradients. My second study analyzed the germination and growth of Microstegium, native grasses, and native woody species in field soils associated with Microstegium invasion. I found that Microstegium-associated soils enhanced Microstegium seed germination, while inhibiting the germination of native grass species. Surprisingly, I found greater aboveground biomass and stem height of native woody species in Microstegium-associated soils; however, I also found increased seedling mortality in Microstegium-associated soils. For my final study, I surveyed Microstegium invasion at the landscape scale in seven local nature reserves to create a habitat suitability analysis using Geographic Information System (GIS) processing. I combined various habitat variables indicative of Microstegium presence to identify areas of greatest habitat suitability. These findings can inform best practices for prevention and eradication of Microstegium. For example, the creation of a habitat suitability analysis for a nature reserve, coupled with the knowledge of the importance of various abiotic factors to Microstegium presence, can assist land managers to direct limited resources to areas of highest susceptibility to invasion or to mitigate population spread

Plant-Soil Feedback Systems in Invasive Grass: Microstegium vimineum

Japanese Stiltgrass (Microstegium vimenium) is an invasive grass that dominates many southeast woodland areas which grows best under sunny conditions but can also thrive in shady areas. We hypothesized that M. vimenium in invaded soils would have higher germination rates as compared to M. vimenium in native soils

Soils Associated with the Invasive Grass: Microstegium vimineum Increases Growth of Native Trees

Soil biota are composed of the animals, plants and microorganisms that interact and share resources and nutrients in the soil. When an invasive species is introduced to this complex web of soil interactions, plants and other biota can exhibit chemical or physical change and potentially inhibit or enhance growth of plant species. By testing five native tree species in a black box experiment, we can see if there is a change in biomass in above ground (AG) or below ground (BG) structures of the tree between invaded soils - which previously hosted an invasive grass, Microstegium vimineum - and native soils that experienced no invasion. There were 6 soils to be tested - from three field sites that held both a native and invaded soil - along with a control soil, resulting in 7 total trial conditions. Invaded soils were found to have significantly more biomass in their aboveground growth through stems and leaves. All of the trials in invaded soils found a higher mean leaf mass than in the native soils trials. We can conclude that the invaded species is altering the biota in the soil. This change could be in nutrient uptake, physical distribution, or chemical interactions of the soil biota. While we don’t know the specific mechanisms behind this, we do know that native tree species will experience more aboveground biomass in soils that experienced invasion, than in soils that did not experience invasion.https://ir.library.louisville.edu/uars/1059/thumbnail.jp

Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inhibitor Discontinuation.

Background: CDK 4 and 6 inhibitors (CDK4/6i), which arrest unregulated cancer cell proliferation, show clinical efficacy in breast cancer. Unexpectedly, a patient treated on a CDK4/6i-based trial, as first-line therapy in metastatic breast cancer, developed rapid disease progression following discontinuation of study drug while receiving standard second-line therapy off trial. We thus sought to expand this observation within a population of patients treated similarly at The University of Texas MD Anderson Cancer Center. Methods: Using an IRB-approved protocol, 4 patients previously enrolled on CDK4/6i trials were analyzed for outcomes after discontinuing study drug. These patients were treated on a randomized trial of first-line endocrine therapy +/- a CDK4/6i. Rapid disease progression was defined as progression occurring within 4 months of CDK4/6i discontinuation. Results: In total, 4 patients developed rapid disease progression and died; 2 of whom died within 6 months of CDK4/6i discontinuation. Conclusion: This case series suggests a potential for rapid disease progression following CDK4/6i discontinuation. However, the clinical course following progression must be validated in large CDK4/6i clinical trials and standard-of-care cohorts. If confirmed, such observations may alter the algorithm for subsequent therapy in patients with disease progression on CDK4/6i. Nevertheless, the need remains to define a mechanistic basis for this rapid progression and formulate alternative therapeutic strategies

Biochemical Evidence for Netrin-Signaling Homologues in Tetrahymena thermophila

Netrins are pleiotropic guidance proteins that are involved in developmental signaling of branched structures within vertebrates. However, like many developmental pathways, dysregulation of the netrin pathway has been implicated in cancer progression and metastasis. Since Tetrahymena respond to guidance proteins, showing chemoattractant and chemorepellent behavior, we hypothesized that we could use these organisms as a model system for cancer signaling. We have previously found that netrin-1-peptided, netrin-3-peptide, and recombinant netrin-4 are all chemorepellents in this organism. Since netrin-1-peptide signals through a tyrosine kinase in Tetrahymena, we hypothesized that Tetrahymena might possess tyrosine kinases as well as a receptor homologous to UNC-5, a netrin receptor which relays signals via tyrosine kinases in vertebrates. Using immunoprecipitation with a polyclonal anti-UNC-5-B antibody, we purified a 250 kD protein from Tetrahymena whole cell extract. Similarly, we immunoprecipitated several proteins, including a 60 kD protein and a 75 kD protein using a polyclonal anti-src-antibody. Our purified samples were sent out for identification by mass spectroscopy. Mass spectroscopy indicated that we have purified a number of novel peptides not currently found in the Tetrahymena Genome Database. Our data indicate that the proteome database in this organism is incomplete, and that there are additional proteins waiting to be discovered in this organism

Short-Term Biomarker Modulation Study of Dasatinib for Estrogen Receptor-Negative Breast Cancer Chemoprevention

OBJECTIVE: Risk-reducing therapy with selective estrogen receptor (ER) modulators and aromatase inhibitors reduce breast cancer risk. However, the effects are limited to ER-positive breast cancer. Therefore, new agents with improved toxicity profiles that reduce the risk in ER-negative breast cancers are urgently needed. The aim of this prospective, short-term, prevention study was to evaluate the effect of dasatinib, an inhibitor of the tyrosine kinase Src, on biomarkers in normal (but increased risk) breast tissue and serum of women at high risk for a second, contralateral primary breast cancer. MATERIALS AND METHODS: Women with a history of unilateral stage I, II, or III ER-negative breast cancer, having no active disease, and who completed all adjuvant therapies were eligible. Patients underwent baseline fine-needle aspiration (FNA) of the contralateral breast and serum collection for biomarker analysis and were randomized to receive either no treatment (control) or dasatinib at 40 or 80 mg/day for three months. After three months, serum collection and breast FNA were repeated. Planned biomarker analysis consisted of changes in cytology and Ki-67 on breast FNA, and changes in serum levels of insulin-like growth factor 1 (IGF-1), IGF-binding protein 1, and IGF-binding protein 3. The primary objective was to evaluate changes in Ki-67 and secondary objective included changes in cytology in breast tissue and IGF-related serum biomarkers. Toxicity was also evaluated. RESULTS: Twenty-three patients started their assigned treatments. Compliance during the study was high, with 86.9% (20/23) of patients completing their assigned doses. Dasatinib was well tolerated and no drug-related grade 3 and 4 adverse events were observed. Since only one patient met the adequacy criteria for the paired FNA sample, we could not evaluate Ki-67 level or cytological changes. No significant change in serum biomarkers was observed among the three groups. CONCLUSION: Dasatinib was well tolerated but did not induce any significant changes in serum biomarkers. The study could not fulfill its primary objective due to an inadequate number of paired FNA samples. Further, larger studies are needed to evaluate the effectiveness of Src inhibitors in breast cancer prevention

Increased levels of the inflammatory biomarker C-reactive protein at baseline are associated with childhood sickle cell vasocclusive crises

Several lines of evidence suggest that sickle cell disease (SCD) is associated with a chronic inflammatory state. In this study of 70 children with SCD at steady state evaluated by a broad panel of biomarkers representing previously examined mechanisms of pathogenicity in SCD, high sensitivity C-reactive protein (hs-CRP), a marker of low-grade, systemic inflammation, emerged as the most significant laboratory correlate of hospitalizations for pain or vaso-occlusive (VOC) events. While markers of increased haemolytic status, endothelial activation and coagulation activation all correlated positively with VOC events by univariate analysis, baseline hs-CRP levels provided the most significant contribution to the association in multiple regression models (22%), and, hs-CRP, along with age, provided the best fit in negative binomial models. These data highlight the clinical relevance of the role of inflammation in paediatric VOC, providing both a rationale for future therapeutic strategies targeting inflammation in microvessel occlusive complications of SCD, and the potential clinical use of hs-CRP as a biomarker in childhood SCD

A Systematic Review of Social Factors and Suicidal Behavior in Older Adulthood

Suicide in later life is a global public health problem. The aim of this review was to conduct a systematic analysis of studies with comparison groups that examined the associations between social factors and suicidal behavior (including ideation, non-fatal suicidal behavior, or deaths) among individuals aged 65 and older. Our search identified only 16 articles (across 14 independent samples) that met inclusion criteria. The limited number of studies points to the need for further research. Included studies were conducted in Canada (n = 2), Germany (n = 1), Hong Kong (n = 1), Japan (n = 1), Singapore (n = 1), Sweden (n = 2), Taiwan (n = 1), the U.K. (n = 2), and the U.S. (n = 3). The majority of the social factors examined in this review can be conceptualized as indices of positive social connectedness—the degree of positive involvement with family, friends, and social groups. Findings indicated that at least in industrialized countries, limited social connectedness is associated with suicidal ideation, non-fatal suicidal behavior, and suicide in later life. Primary prevention programs designed to enhance social connections as well as a sense of community could potentially decrease suicide risk, especially among men

Circulating 25-Hydroxyvitamin D and the Risk of Rarer Cancers: Design and Methods of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP), a consortium of 10 prospective cohort studies from the United States, Finland, and China, was formed to examine the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of rarer cancers. Cases (total n = 5,491) included incident primary endometrial (n = 830), kidney (n = 775), ovarian (n = 516), pancreatic (n = 952), and upper gastrointestinal tract (n = 1,065) cancers and non-Hodgkin lymphoma (n = 1,353) diagnosed in the participating cohorts. At least 1 control was matched to each case on age, date of blood collection (1974–2006), sex, and race/ethnicity (n = 6,714). Covariate data were obtained from each cohort in a standardized manner. The majority of the serum or plasma samples were assayed in a central laboratory using a direct, competitive chemiluminescence immunoassay on the DiaSorin LIAISON platform (DiaSorin, Inc., Stillwater, Minnesota). Masked quality control samples included serum standards from the US National Institute of Standards and Technology. Conditional logistic regression analyses were conducted using clinically defined cutpoints, with 50–<75 nmol/L as the reference category. Meta-analyses were also conducted using inverse-variance weights in random-effects models. This consortium approach permits estimation of the association between 25(OH)D and several rarer cancers with high accuracy and precision across a wide range of 25(OH)D concentrations