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In the adult central nervous system, the vasculature of the neurogenic niche regulates neural stem cell behavior by providing circulating and secreted factors. Age-related decline of neurogenesis and cognitive function is associated with reduced blood flow and decreased numbers of neural stem cells. Therefore, restoring the functionality of the niche should counteract some of the negative effects of aging. We show that factors found in young blood induce vascular remodeling, culminating in increased neurogenesis and improved olfactory discrimination in aging mice. Further, we show that GDF11 alone can improve the cerebral vasculature and enhance neurogenesis. The identification of factors that slow the age-dependent deterioration of the neurogenic niche in mice may constitute the basis for new methods of treating age-related neurodegenerative and neurovascular diseases.

Increasing biological nitrogen (N) fixation (BNF) in maize production could reduce the environmental impacts of N fertilizer use, but reactive N in the rhizosphere of maize limits the BNF process. Using non-transgenic methods, we developed gene-edited strains of Klebsiella variicola ( Kv 137-2253) and Kosakonia sacchari ( Ks 6-5687) bacteria optimized for root-associated BNF and ammonium excretion in N-rich conditions. The aim of this research was to elucidate the mechanism of action of these strains. We present evidence from in vitro, in planta and field experiments that confirms that our genetic remodeling strategy derepresses BNF activity in N-rich systems and increases ammonium excretion by orders of magnitude above the respective wildtype strains. BNF is demonstrated in controlled environments by the transfer of labeled 15 N 2 gas from the rhizosphere to the chlorophyll of inoculated maize plants. This was corroborated in several 15 N isotope tracer field experiments where inoculation with the formulated, commercial-grade product derived from the gene-edited strains (PIVOT BIO PROVEN® 40) provided on average 21 kg N ha -1 to the plant by the VT-R1 growth stages. Data from small-plot and on-farm trials suggest that this technology can improve crop N status pre-flowering and has potential to mitigate the risk of yield loss associated with a reduction in synthetic N fertilizer inputs.

Soft-tissue sarcomas are heterogeneous cancers that can present with tissue-specific differentiation markers. To examine the cellular basis for this histopathological variation and to identify sarcoma-relevant molecular pathways, we generated a chimeric mouse model in which sarcoma-associated genetic lesions can be introduced into discrete, muscle-resident myogenic and mesenchymal cell lineages. Expression of Kirsten rat sarcoma viral oncogene [Kras(G12V)] and disruption of cyclin-dependent kinase inhibitor 2A (CDKN2A; p16p19) in prospectively isolated satellite cells gave rise to pleomorphic rhabdomyosarcomas (MyoD-, Myogenin- and Desmin-positive), whereas introduction of the same oncogenetic hits in nonmyogenic progenitors induced pleomorphic sarcomas lacking myogenic features. Transcriptional profiling demonstrated that myogenic and nonmyogenic Kras; p16p19null sarcomas recapitulate gene-expression signatures of human rhabdomyosarcomas and identified a cluster of genes that is concordantly up-regulated in both mouse and human sarcomas. This cluster includes genes associated with Ras and mechanistic target of rapamycin (mTOR) signaling, a finding consistent with activation of the Ras and mTOR pathways both in Kras; p16p19null sarcomas and in 26–50% of human rhabdomyosarcomas surveyed. Moreover, chemical inhibition of Ras or mTOR signaling arrested the growth of mouse Kras; p16p19null sarcomas and of human rhabdomyosarcoma cells in vitro and in vivo. Taken together, these data demonstrate the critical importance of lineage commitment within the tumor cell-of-origin in determining sarcoma histotype and introduce an experimental platform for rapid dissection of sarcoma-relevant cellular and molecular events.

Since its emergence in late 2019, SARS-CoV-2 has infected over 15 million people—and the number continues to rise. The global impact of this novel coronavirus has been profound, reshaping not only public health infrastructure but also our understanding of human biology. The full extent of the virus’s effects on the immune system remains incompletely understood and will likely take years to fully unravel. What is already evident, however, is that SARS-CoV-2 uniquely modulates both innate and adaptive immunity, with consequences that span the developmental spectrum—from fetal and pediatric stages through adulthood. While many individuals recover without overt clinical sequelae, an increasing subset experience persistent symptoms and immune dysregulation. This thesis aims to investigate these enduring consequences, with a focus on individuals demonstrating long-term impact. Through a combination of epidemiologic analysis and immunological profiling, this work seeks to deepen our understanding of the biological underpinnings of this complex and emerging clinical entity.This thesis explores the evolving clinical entity of Long COVID within the broader framework of Post-Acute Infection Syndromes (PAIS)—a poorly understood area of medicine in which certain individuals experience prolonged signs and symptoms following acute infection. While Long COVID is often regarded as a novel condition, there is a longstanding historical precedent for post-acute syndromes following both viral and bacterial infections, particularly in the aftermath of epidemics. The first chapter provides a conceptual foundation for PAIS, emphasizing the urgent need for further investigation and clinical characterization of these syndromes.Chapter two presents a scoping review of all U.S.-based studies on pediatric Long COVID, summarizing current knowledge on its epidemiology. Across studies, adolescent females were disproportionately affected. Fatigue, headache, and chest pain emerged as the most commonly reported symptoms. Estimated prevalence varied widely—from less than 1% to 27%—with identified risk factors including older age, female sex, asthma, obesity, and severity of acute infection. Most studies suffered from methodological limitations, including inconsistent case definitions and limited follow-up.Chapter three focuses on saliva as a promising exploratory biospecimen. While blood remains the gold standard for immunologic assessment, saliva offers distinct advantages, particularly its non-invasive collection, feasibility for serial sampling, and accessibility in pediatric and hard-to-reach populations. These features make it especially valuable for studying syndromes requiring longitudinal observation.The final chapter details our own study leveraging saliva to investigate immunologic differences in individuals with Long COVID compared to controls. We found that participants with Long COVID exhibited significantly lower levels of SARS-CoV-2-specific IgG and IgA in saliva, suggesting potential mucosal immune dysregulation in this population. In sum, this thesis contributes to both the epidemiologic and immunologic understanding of Long COVID, situating it within the wider landscape of post-acute infection syndromes. SARS-CoV-2 presents a rare and important opportunity to examine the long-term consequences of a well-characterized acute viral infection, offering critical insights into the mechanisms underlying persistent illness following infection.

A study surveyed small business owner/managers to identify the information sources they used to deal with various issues, and to determine the factors that affect their choices of sources. The results suggest that the more important the decision and the more the manager perceives himself or herself to be effective in making a particular type of decision, the greater the intensity of the information search, and the greater the use of external information sources during the decision-making.

Sustainable forage farming systems must precisely match nitrogen (N) applications to crop needs to minimize environmental N losses and meet crop yield goals. Successfully executing N management plans is especially challenging in manure fertilized cropping systems because manure is highly variable and contains a large proportion of organic N. To reduce N leaching to groundwater, California dairy farmers must limit the ratio of N applied to N removed from cropland (N Ratio) to 1.4. Farmers quantify their N application rates by sampling and analyzing the N concentration of their manures, and by measuring the weight or volume of manure when it is applied. This dissertation quantifies the extent and impacts of uncertainty in N application and removal measurements in manure based forage cropping systems. These measurements must be accurate enough to identify N Ratios that will support crop yields while preventing excess N leaching to groundwater. The validity of the data collected by dairy farmers to quantify their N application and removal rates was investigated using mass balance analysis in Chapter 2. First, the N, phosphorus (P), and potassium (K) excreted by cattle on 62 facilities was modeled and compared with the amount of nutrients recovered in manures exported off-farm or applied to cropland. Less N and P were recovered than expected given possible volatile losses during storage. Second, reported N Ratios were compared with N Ratios that simulated unavoidable environmental losses over three cropping years. Analyses showed that reported N application rates were too low to maintain reported crop yields. Overall, reported data was not consistent with mass balance analysis indicating substantial inaccuracies in measurements of N application and removal. The uncertainty in farmer measurements of the N removed in harvested forage and the N concentration of solid manure was quantified in Chapters 3 and 4, respectively. The N harvested from 9 forage fields and the N concentration of 10 solid manure piles to was intensively measured to estimate the 'true' value. Resampling simulations were used to assess the accuracy of less intensive measurement protocols relative to the 'true' value. Measurements of N removed in harvested forage were accurate within$\\pm$ 5\\% if every truckload of forage was weighed and 10 grab samples were composited for nutrient analysis. Measurements of N concentration of solid manure were accurate within$\\pm$ 10\\% if 10 grab samples were composited for nutrient analysis and 70\\% of samples were collected from greater than 40 cm into the manure pile. The uncertainty of total N application, N Ratios, and groundwater nitrate leaching rates was quantified in Chapter 5. A stochastic model of total N application was built using Monte Carlo methods to propagate the uncertainty from underlying measurements. The stochastic N application model was used to vary the N applications of two representative forage fields around farmer reported values for 5 years. The N Ratios and groundwater nitrate loading rates were simulated for the stochastic N application scenarios using HYDRUS 1D water and solute transport model and compared to monitoring well measurements. Results suggested that reducing uncertainty in process wastewater measurements is required to meaningfully judge the effectiveness of N Ratio limitations and reduce N losses to groundwater. Greater measurement accuracy of manure N application is required before nitrate leaching to groundwater can be further reduced. This dissertation provides many practical suggestions for efficiently improving the accuracy of N application and removal measurements in manure based cropping systems. Measurements that quantify N application must be accurate enough to identify and execute suggested management improvements before we will be able to reliably reduce environmental N losses.

Nonprofits are subject to state laws and are governed in a way that firm or corporate attorneys may not encounter in their law practices.

The U.S. workforce is becoming more demographically diverse (Johnson & Packer, 1987). At the same time, an increasing proportion of American workers hold jobs which require teamwork (Sundstrom, DeMeuse, & Futrell, 1990). Yet, there is little research which examines how cultural or ethnic differences influence group behavior (Bettenhausen, 1991; Levine & Moreland, 1990). The present study was directed toward addressing this deficit within the group literature. The purpose of this study was to examine whether the level of cultural heterogeneity within the membership of a group would influence group processes and outcomes. Cross-cultural studies have shown that people from different cultural backgrounds possess different norms and values. An underlying premise of recent organizational studies (e.g. Cox, Lobel, & McLeod, 1991; Earley, 1991) has been that cultural norms and values will influence work-relevant behaviors. A central premise of this study was that differences in cultural values would manifest themselves in behaviors relevant to group member interactions, thus influencing group processes and outcomes. Specifically, this study tested a structural equations model derived from a synthesis of group theory and organizational demography. The overall model was analyzed using LISREL. Individual hypotheses predicted that increased levels of ethnic diversity within a group would be associated with decreased levels of group cohesiveness, group performance, absenteeism, turnover, and member satisfaction. Participants in this study were members of naturally occurring, intact groups. One hundred sixty-three students in 38 groups performed a group analysis of a strategic management case and individually completed questionnaires. Findings suggest that ethnic heterogeneity has no significant influence on group processes and outcomes. That is, no significant differences were observed between ethnically diverse and ethnically homogeneous groups with regard to levels of group cohesiveness, group performance, member satisfaction, and absenteeism. There was limited evidence, however, to suggest that age and gender diversity do influence group behavior. Specifically, increased levels of age/gender diversity in a group tended to be associated with lower levels of group cohesiveness and member satisfaction, and higher levels of group performance on an unstructured task. Implications for organizational theory and practice are discussed, along with directions for future research.