A comparative genomics approach to identifying the plasticity transcriptome

BACKGROUND: Neuronal activity regulates gene expression to control learning and memory, homeostasis of neuronal function, and pathological disease states such as epilepsy. A great deal of experimental evidence supports the involvement of two particular transcription factors in shaping the genomic response to neuronal activity and mediating plasticity: CREB and zif268 (egr-1, krox24, NGFI-A). The gene targets of these two transcription factors are of considerable interest, since they may help develop hypotheses about how neural activity is coupled to changes in neural function. RESULTS: We have developed a computational approach for identifying binding sites for these transcription factors within the promoter regions of annotated genes in the mouse, rat, and human genomes. By combining a robust search algorithm to identify discrete binding sites, a comparison of targets across species, and an analysis of binding site locations within promoter regions, we have defined a group of candidate genes that are strong CREB- or zif268 targets and are thus regulated by neural activity. Our analysis revealed that CREB and zif268 share a disproportionate number of targets in common and that these common targets are dominated by transcription factors. CONCLUSION: These observations may enable a more detailed understanding of the regulatory networks that are induced by neural activity and contribute to the plasticity transcriptome. The target genes identified in this study will be a valuable resource for investigators who hope to define the functions of specific genes that underlie activity-dependent changes in neuronal properties

First-Year Engineering Program: Student Instructional Leadership Team - Expanded and Restructured

Since its initial creation, the Student Instructional Leadership Team (SILT) within the First-Year Engineering Program (FEP) at The Ohio State University (OSU) has been responsible for training and supporting students and instructional staff. In recent years, SILT has been expanded and restructured to meet the needs of a growing student body and ever-changing program. SILT currently has 13 members working across all 4 tracks of FEP. This team helps manage over 2,000 students and 200 teaching assistants (TAs). SILT assists with various FEP resources such as its computer lab and laboratories. SILT also provides professional development opportunities for student employees. Furthermore, the leadership team strives to enhance the program’s learning objectives, support curriculum enhancements, and create consistency. Through continued change and improvement, SILT has become a model for involving TAs in the management of a large scale educational unit such as FEP

Benchmarking impact of nitrogen inputs on grain yield and environmental performance of producer fields in the western US Corn Belt

Benchmarking crop yields against nitrogen (N) input levels can help provide opportunities to improve N ferti-lizer efficiency and reduce N losses on maize in the US Corn Belt by identifying fields most likely to benefit from improved N management practices. Here, we evaluated a large producer database that includes field-level data on yield and applied N inputs from 9280 irrigated and rainfed fields over a 7-year period (2009–2015) in Nebraska (USA). A spatial framework, based on technology extrapolation domains, was used to cluster each field into spatial units with similar climate and soil type that represent 1.3 million ha of US farm land sown annually with maize. Three metrics were employed to evaluate agronomic and environmental performance: partial factor productivity for N inputs (PFPN, ratio between yield and N inputs), N balance (difference between N inputs and grain N removal), and yield-scaled N balance (ratio between N balance and yield). Nitrogen inputs included N from fertilizer and N contained in applied irrigation water. Average yield and N inputs were 40 and 44% higher in irrigated versus rainfed fields. The N balance was ca. 2-fold greater in irrigated versus rainfed fields (81 versus 41 kg N ha−1). Of the total number of field-years, 58% (irrigated) and 15% (rainfed) had N balance ≥ 75 kg N ha−1, which was considered a threshold to identify fields with potentially large N losses. Very large (\u3e 150 kg N ha−1) and negative N balance estimates were not apparent when analysis was based on field averages using a minimum of three years\u27 data instead of individual field-years. Nitrogen balance was smaller for maize crops following soybean compared to continuous maize. Despite the larger N balance (on an area basis), irrigated fields exhibited smaller yield-scaled N balance relative to rainfed fields. The approach proposed here can readily be adopted to benchmark current use of N fertilizer for other cereal-based crop systems, inform policy, and identify opportunities for improvement in N management

Benchmarking impact of nitrogen inputs on grain yield and environmental performance of producer fields in the western US Corn Belt

Benchmarking crop yields against nitrogen (N) input levels can help provide opportunities to improve N ferti-lizer efficiency and reduce N losses on maize in the US Corn Belt by identifying fields most likely to benefit from improved N management practices. Here, we evaluated a large producer database that includes field-level data on yield and applied N inputs from 9280 irrigated and rainfed fields over a 7-year period (2009–2015) in Nebraska (USA). A spatial framework, based on technology extrapolation domains, was used to cluster each field into spatial units with similar climate and soil type that represent 1.3 million ha of US farm land sown annually with maize. Three metrics were employed to evaluate agronomic and environmental performance: partial factor productivity for N inputs (PFPN, ratio between yield and N inputs), N balance (difference between N inputs and grain N removal), and yield-scaled N balance (ratio between N balance and yield). Nitrogen inputs included N from fertilizer and N contained in applied irrigation water. Average yield and N inputs were 40 and 44% higher in irrigated versus rainfed fields. The N balance was ca. 2-fold greater in irrigated versus rainfed fields (81 versus 41 kg N ha−1). Of the total number of field-years, 58% (irrigated) and 15% (rainfed) had N balance ≥ 75 kg N ha−1, which was considered a threshold to identify fields with potentially large N losses. Very large (\u3e 150 kg N ha−1) and negative N balance estimates were not apparent when analysis was based on field averages using a minimum of three years\u27 data instead of individual field-years. Nitrogen balance was smaller for maize crops following soybean compared to continuous maize. Despite the larger N balance (on an area basis), irrigated fields exhibited smaller yield-scaled N balance relative to rainfed fields. The approach proposed here can readily be adopted to benchmark current use of N fertilizer for other cereal-based crop systems, inform policy, and identify opportunities for improvement in N management

Novel enrichment reduces boredom-associated behaviours in housed dairy cows

There is currently societal interest and concern for dairy cow welfare. It has been suggested that boredom poses a welfare issue for dairy cows, particularly when presented with extended disposable time in housed environments that lack stimuli. Farm animals experience a multitude of affective states, which has created a need for positive experiences to be included in welfare management. Environmental enrichment can reduce boredom and facilitate positive experiences however the research in cows is limited. To assess the behavioral impact of a simple enrichment on commercially housed dairy cows, we provided 24-h access to a novel object, for 3 weeks, for 2 separate groups of cows. Two boredom-associated behaviors significantly decreased when the object was present compared with when it was not present: ‘idling' behavior and unsuccessful robotic milking attempts ‘refusals'. In addition, there was a significant increase in the occurrence of self-grooming during treatment weeks, when the novel object was present. These results suggest that idling and refusals may be behavioral indicators of boredom in dairy cows

Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction

Diabetes, obesity and Alzheimer’s disease (AD) are associated with vascular complications and impaired nitric oxide (NO) production. Furthermore, increased β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), APP and β-amyloid (Aβ) are linked with vascular disease development and raised BACE1 and Aβ accompany hyperglycemia and hyperlipidemia. However, the causal relationship between obesity and diabetes, raised Aβ and vascular dysfunction is unclear. We report that diet-induced obesity (DIO) in mice raised plasma and vascular Aβ42 that correlated with decreased NO bioavailability, endothelial dysfunction and raised blood pressure. Genetic or pharmacological reduction of BACE1 activity and Aβ42 prevented and reversed, respectively, these outcomes. In contrast, expression of human mutant APP in mice or Aβ42 infusion into control diet-fed mice to mimic obese levels impaired NO production, vascular relaxation and raised blood pressure. In humans, raised plasma Aβ42 correlated with diabetes and endothelial dysfunction. Mechanistically, higher Aβ42 reduced endothelial NO synthase (eNOS), cyclic GMP and protein kinase G (PKG) activity independently of diet whereas endothelin-1 was increased by diet and Aβ42. Lowering Aβ42 reversed the DIO deficit in the eNOS-cGMP-PKG pathway and decreased endothelin-1. Our findings suggest that BACE1 inhibitors may have therapeutic value in the treatment of vascular disease associated with diabetes

Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production

Semi-synthetic derivatives of the tricyclic diterpene antibiotic pleuromutilin from the basidiomycete Clitopilus passeckerianus are important in combatting bacterial infections in human and veterinary medicine. These compounds belong to the only new class of antibiotics for human applications, with novel mode of action and lack of cross-resistance, representing a class with great potential. Basidiomycete fungi, being dikaryotic, are not generally amenable to strain improvement. We report identification of the seven-gene pleuromutilin gene cluster and verify that using various targeted approaches aimed at increasing antibiotic production in C. passeckerianus, no improvement in yield was achieved. The seven-gene pleuromutilin cluster was reconstructed within Aspergillus oryzae giving production of pleuromutilin in an ascomycete, with a significant increase (2106%) in production. This is the first gene cluster from a basidiomycete to be successfully expressed in an ascomycete, and paves the way for the exploitation of a metabolically rich but traditionally overlooked group of fungi