Genetic and Biotechnological Approaches to Improve Fruit Bioactive Content: A Focus on Eggplant and Tomato Anthocyanins.

Anthocyanins are a large group of water-soluble flavonoid pigments. These specialized metabolites are ubiquitous in the plant kingdom and play an essential role not only in plant reproduction and dispersal but also in responses to biotic and abiotic stresses. Anthocyanins are recognized as important health-promoting and chronic-disease-preventing components in the human diet. Therefore, interest in developing food crops with improved levels and compositions of these important nutraceuticals is growing. This review focuses on work conducted to elucidate the genetic control of the anthocyanin pathway and modulate anthocyanin content in eggplant (Solanum melongena L.) and tomato (Solanum lycopersicum L.), two solanaceous fruit vegetables of worldwide relevance. While anthocyanin levels in eggplant fruit have always been an important quality trait, anthocyanin-based, purple-fruited tomato cultivars are currently a novelty. As detailed in this review, this difference in the anthocyanin content of the cultivated germplasm has largely influenced genetic studies as well as breeding and transgenic approaches to improve the anthocyanin content/profile of these two important solanaceous crops. The information provided should be of help to researchers and breeders in devising strategies to address the increasing consumer demand for nutraceutical foods.

Imaging breast cancer using hyperpolarized carbon-13 MRI.

Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2-), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2- invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

Deuterium metabolic imaging and hyperpolarized 13C-MRI of the normal human brain at clinical field strength reveals differential cerebral metabolism.

Deuterium metabolic imaging (DMI) and hyperpolarized 13C-pyruvate MRI (13C-HPMRI) are two emerging methods for non-invasive and non-ionizing imaging of tissue metabolism. Imaging cerebral metabolism has potential applications in cancer, neurodegeneration, multiple sclerosis, traumatic brain injury, stroke, and inborn errors of metabolism. Here we directly compare these two non-invasive methods at 3 T for the first time in humans and show how they simultaneously probe both oxidative and non-oxidative metabolism. DMI was undertaken 1-2 h after oral administration of [6,6'-2H2]glucose, and 13C-MRI was performed immediately following intravenous injection of hyperpolarized [1-13C]pyruvate in ten and nine normal volunteers within each arm respectively. DMI was used to generate maps of deuterium-labelled water, glucose, lactate, and glutamate/glutamine (Glx) and the spectral separation demonstrated that DMI is feasible at 3 T. 13C-HPMRI generated maps of hyperpolarized carbon-13 labelled pyruvate, lactate, and bicarbonate. The ratio of 13C-lactate/13C-bicarbonate (mean 3.7 ± 1.2) acquired with 13C-HPMRI was higher than the equivalent 2H-lactate/2H-Glx ratio (mean 0.18 ± 0.09) acquired using DMI. These differences can be explained by the route of administering each probe, the timing of imaging after ingestion or injection, as well as the biological differences in cerebral uptake and cellular physiology between the two molecules. The results demonstrate these two metabolic imaging methods provide different yet complementary readouts of oxidative and reductive metabolism within a clinically feasible timescale. Furthermore, as DMI was undertaken at a clinical field strength within a ten-minute scan time, it demonstrates its potential as a routine clinical tool in the future.

Familial pseudohyperkalemia induces significantly higher levels of extracellular potassium in early storage of red cell concentrates without affecting other standard measures of quality: A case control and allele frequency study.

BACKGROUND: Familial pseudohyperkalemia (FP) is characterized by an increased rate of potassium leakage in refrigerated red cells and is associated with the minor allele of the single nucleotide polymorphism rs148211042 (R723Q) in the ABCB6 gene. The study aims were to obtain the minor allele frequencies of ABCB6 variants and to measure supernatant potassium accumulation, and other red cell storage parameters, in red cell concentrates (RCC) from carriers of variant rs148211042 under standard blood bank conditions. STUDY DESIGN: Whole blood units were collected from 6 FP individuals and 11 controls and processed into RCC in additive solution. RCC were sampled and tested over cold storage for full blood count, extracellular potassium, glucose, lactate, microvesicle release, deformability, hemolysis, pH, adenosine triphosphate, and 2,3-diphosphoglycerate. RESULTS: Screening of genotyped cohorts identified that variant rs148211042 is present in 1 in 394 British citizens of European ancestry. FP RCC had significantly higher supernatant potassium at all time points from day 3 onwards (p < .001) and higher mean cell volume (p = .032) than controls. The initial rate of potassium release was higher in FP RCC; supernatant potassium reached 46.0 (23.8-57.6) mmol/L (mean [range]) by day 5, increasing to 68.9 (58.8-73.7) mmol/L by day 35. Other quality parameters were not significantly different between FP RCC and controls. CONCLUSION: These data suggest that if a blood donor has FP, reducing the RCC shelf-life to 5 days may be insufficient to reduce the risk of hyperkalemia in clinical scenarios such as neonatal large volume transfusion.

Non-contrast MRI can accurately characterize adnexal masses: a retrospective study.

OBJECTIVE: To determine the accuracy of interpretation of a non-contrast MRI protocol in characterizing adnexal masses. METHODS AND MATERIALS: Two hundred ninety-one patients (350 adnexal masses) who underwent gynecological MRI at our institution between the 1st of January 2008 and the 31st of December 2018 were reviewed. A random subset (102 patients with 121 masses) was chosen to evaluate the reproducibility and repeatability of readers' assessments. Readers evaluated non-contrast MRI scans retrospectively, assigned a 5-point score for the risk of malignancy and gave a specific diagnosis. The reference standard for the diagnosis was histopathology or at least one-year imaging follow-up. Diagnostic accuracy of the non-contrast MRI score was calculated. Inter- and intra-reader agreement was analyzed with Cohen's kappa statistics. RESULTS: There were 53/350 (15.1%) malignant lesions in the whole cohort and 20/121 (16.5%) malignant lesions in the random subset. Good agreement between readers was found for the non-contrast MRI score (к = 0.73, 95% confidence interval [CI] 0.58-0.86) whilst the intra-reader agreement was excellent (к = 0.81, 95% CI 0.70-0.88). The non-contrast MRI score value of ≥ 4 was associated with malignancy with a sensitivity of 84.9%, a specificity of 95.9%, an accuracy of 94.2% and a positive likelihood ratio of 21 (area under the receiver operating curve 0.93, 95% CI 0.90-0.96). CONCLUSION: Adnexal mass characterization on MRI without the administration of contrast medium has a high accuracy and excellent inter- and intra-reader agreement. Our results suggest that non-contrast studies may offer a reasonable diagnostic alternative when the administration of intravenous contrast medium is not possible. KEY POINTS: • A non-contrast pelvic MRI protocol may allow the characterization of adnexal masses with high accuracy. • The non-contrast MRI score may be used in clinical practice for differentiating benign from malignant adnexal lesions when the lack of intravenous contrast medium precludes analysis with the O-RADS MRI score.

Analysis of European hazelnut (Corylus avellana) reveals loci for cultivar improvement and the effects of domestication and selection on nut and kernel traits.

Turkey is a rich source of European hazelnut (Corylus avellana) germplasm with nearly 400 accessions in the national collection. This genetic material encompasses cultivars, landraces and wild genotypes which were characterized for 12 nut and 13 kernel traits over 2 years in the 1990s. Analysis of these attributes revealed both the positive and negative impacts that human selection and breeding have had on hazelnut. Thus, while selection has resulted in larger nuts and kernels, cultivars have fewer nuts per cluster and kernels with larger internal cavities. Breeding has also resulted in a propensity for cultivars to have higher proportions of double kernels and empty nuts, two traits which reduce quality and yield. In addition, it is clear that while selection has successfully increased hazelnut fat content it has not impacted overall flavor, a much more complex trait. The nut and kernel phenotypic data were combined with genotypic data from 406 simple sequence repeat marker alleles for association mapping of the quantitative trait loci (QTL) for the traits. A total of 78 loci were detected in the population with the highest proportions for nut (24%) and kernel (26%) appearance parameters followed by quality (19%), shell thickness (16%) and yield-related (15%) traits. It is hoped that some of the identified QTL will be useful for future breeding of hazelnut for improved nut and kernel yield and quality.

SMIM1 absence is associated with reduced energy expenditure and excess weight.

BACKGROUND: Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments. METHODS: We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan. FINDINGS: We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure. CONCLUSION: This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them. FUNDING: This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.

Glioblastomas with oligodendroglial component have the same clinical phenotype as classical glioblastomas.

INTRODUCTION: Glioblastomas are the commonest primary brain tumour and are considered one of the most heterogeneous tumour types. The introduction of a glioblastoma with oligodendroglial component (GBM + O) in the latest WHO Classification of Tumours of the Central Nervous System (1) was to help with this. There has been conflicting evidence as to whether this tumour conferred a better prognosis than classical glioblastoma (GBM). The aim of this study was to study the clinical phenotype of these GBM + O tumours and compare it to the classical GBM. MATERIALS AND METHODS: All patients with histological evidence of a glioblastoma between 1st January 2007 and 31st January 2011 were identified from the Neuropathology Database. Clinical and radiological details were obtained for all patients. The overall survival of patients who were treated with chemoradiotherapy was obtained and the GBM + O cohort compared to the classical GBM cohort. RESULTS: Three hundred and ninety-six patients with newly diagnosed glioblastomas were identified: 294 (74.2%) had classical GBM and 102 (25.6%) had GBM + O. The two cohorts presented at a similar age (61.1 years GBM + O vs. 63.2 years GBM; P = 0.09) and were matched for sex and side of the tumour. GBM + O were more likely to be located in the frontal lobes (38.2% for GBM + O vs. 27.2% for GBM: P = 0.04). In the group that was treated with chemoradiotherapy the overall survival was similar (median survival GBM + O 361 days vs. 379 days GBM; Log Rank 0.61, P = 0.43). CONCLUSION: The presence of an oligodendroglial component does not confer any improvement in survival and has a similar clinical phenotype to classical GBMs.

Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.

Hyperpolarised magnetic resonance imaging (HP 13C-MRI) is an emerging clinical technique to detect [1-13C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-13C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/intermediate-risk population by correlating [1-13C]lactate labelling on MRI with the percentage of Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, we show that HP 13C-MRI predominantly measures metabolism in the epithelial compartment of the tumour, rather than the stroma. MRI-derived tumour [1-13C]lactate labelling correlated with epithelial mRNA expression of the enzyme lactate dehydrogenase (LDHA and LDHB combined), and the ratio of lactate transporter expression between the epithelial and stromal compartments (epithelium-to-stroma MCT4). We observe similar changes in MCT4, LDHA, and LDHB between tumours with primary Gleason patterns 3 and 4 in an independent TCGA cohort. Therefore, HP 13C-MRI can metabolically phenotype clinically significant disease based on underlying metabolic differences in the epithelial and stromal tumour compartments.

Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.

Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.

Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes.

BACKGROUND: This work is aimed at improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature. METHODS/RESULTS: We combined classic plasma biochemistry and plasma biomarkers with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (morbidly obese and lipodystrophy) and lean individuals to identify the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells. Our analyses showed that extreme phenotype groups could be distinguished from lean individuals, and from each other, across all data layers. The characterisation of the same obese group, 6 months after bariatric surgery, revealed the loss of the abnormal activation of innate immune cells previously observed. However, rather than reverting to the gene expression landscape of lean individuals, this occurred via the establishment of novel gene expression landscapes. NETosis and its control mechanisms emerge amongst the pathways that show an improvement after surgical intervention. CONCLUSIONS: We showed that the morbidly obese and lipodystrophy groups, despite some differences, shared a common cardiometabolic syndrome signature. We also showed that this could be used to discriminate, amongst the normal population, those individuals with a higher likelihood of presenting with the disease, even when not displaying the classic features.

Imaging Glioblastoma Metabolism by Using Hyperpolarized [1-13C]Pyruvate Demonstrates Heterogeneity in Lactate Labeling: A Proof of Principle Study.

Purpose To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (13C) MRI to monitor the exchange of the hyperpolarized 13C label between injected [1-13C]pyruvate and tumor lactate and bicarbonate. Materials and Methods In this prospective study, seven treatment-naive patients (age [mean ± SD], 60 years ± 11; five men) with GBM were imaged at 3 T by using a dual-tuned 13C-hydrogen 1 head coil. Hyperpolarized [1-13C]pyruvate was injected, and signal was acquired by using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchyma (NABP), and in healthy volunteers by using paired or unpaired t tests and a Wilcoxon signed rank test. The Spearman ρ correlation coefficient was used to correlate metabolite labeling with lactate dehydrogenase A (LDH-A) expression and some immunohistochemical markers. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. Results The bicarbonate-to-pyruvate (BP) ratio was lower in the tumor than in the contralateral NABP (P < .01). The tumor lactate-to-pyruvate (LP) ratio was not different from that in the NABP (P = .38). The LP and BP ratios in the NABP were higher than those observed previously in healthy volunteers (P < .05). Tumor lactate and bicarbonate signal intensities were strongly correlated with the pyruvate signal intensity (ρ = 0.92, P < .001, and ρ = 0.66, P < .001, respectively), and the LP ratio was weakly correlated with LDH-A expression in biopsy samples (ρ = 0.43, P = .04). Conclusion Hyperpolarized 13C MRI demonstrated variation in lactate labeling in GBM, both within and between tumors. In contrast, bicarbonate labeling was consistently lower in tumors than in the surrounding NABP. Keywords: Hyperpolarized 13C MRI, Glioblastoma, Metabolism, Cancer, MRI, Neuro-oncology Supplemental material is available for this article. Published under a CC BY 4.0 license.

Multiparametric MRI of early tumor response to immune checkpoint blockade in metastatic melanoma.

BACKGROUND: Immune checkpoint inhibitors are now standard of care treatment for many cancers. Treatment failure in metastatic melanoma is often due to tumor heterogeneity, which is not easily captured by conventional CT or tumor biopsy. The aim of this prospective study was to investigate early microstructural and functional changes within melanoma metastases following immune checkpoint blockade using multiparametric MRI. METHODS: Fifteen treatment-naïve metastatic melanoma patients (total 27 measurable target lesions) were imaged at baseline and following 3 and 12 weeks of treatment on immune checkpoint inhibitors using: T2-weighted imaging, diffusion kurtosis imaging, and dynamic contrast-enhanced MRI. Treatment timepoint changes in tumor cellularity, vascularity, and heterogeneity within individual metastases were evaluated and correlated to the clinical outcome in each patient based on Response Evaluation Criteria in Solid Tumors V.1.1 at 1 year. RESULTS: Differential tumor growth kinetics in response to immune checkpoint blockade were measured in individual metastases within the same patient, demonstrating significant intertumoral heterogeneity in some patients. Early detection of tumor cell death or cell loss measured by a significant increase in the apparent diffusivity (Dapp) (p<0.05) was observed in both responding and pseudoprogressive lesions after 3 weeks of treatment. Tumor heterogeneity, as measured by apparent diffusional kurtosis (Kapp), was consistently higher in the pseudoprogressive and true progressive lesions, compared with the responding lesions throughout the first 12 weeks of treatment. These preceded tumor regression and significant tumor vascularity changes (Ktrans, ve, and vp) detected after 12 weeks of immunotherapy (p<0.05). CONCLUSIONS: Multiparametric MRI demonstrated potential for early detection of successful response to immune checkpoint inhibitors in metastatic melanoma.

Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients.

Hyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1-13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7-11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5-6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. SIGNIFICANCE: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7-11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.

Hyperpolarized 13C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer.

Purpose: To compare hyperpolarized carbon 13 (13C) MRI with dynamic contrast material-enhanced (DCE) MRI in the detection of early treatment response in breast cancer. Materials and Methods: In this institutional review board-approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent 13C MRI after injection of hyperpolarized [1-carbon 13 {13C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The 13C-labeled lactate-to-pyruvate ratio derived from hyperpolarized 13C MRI and the pharmacokinetic parameters transfer constant (K trans) and washout parameter (k ep) derived from DCE MRI were compared before and after treatment. Results: Exchange of the 13C label between injected hyperpolarized [1-13C]-pyruvate and the endogenous lactate pool was observed, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the 13C-labeled lactate-to-pyruvate ratio resulted in correct identification of the patient as a responder to therapy, which was subsequently confirmed via a complete pathologic response. However, DCE MRI showed an increase in mean K trans (132%) and mean k ep (31%), which could be incorrectly interpreted as a poor response to treatment. Conclusion: Hyperpolarized 13C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI.Published under a CC BY 4.0 license.

Health benefits and bioactive compounds of eggplant.

Eggplant is a vegetable crop that is grown around the world and can provide significant nutritive benefits thanks to its abundance of vitamins, phenolics and antioxidants. In addition, eggplant has potential pharmaceutical uses that are just now becoming recognized. As compared to other crops in the Solanaceae, few studies have investigated eggplant's metabolic profile. Metabolomics and metabolic profiling are important platforms for assessing the chemical composition of plants and breeders are increasingly concerned about the nutritional and health benefits of crops. In this review, the historical background and classification of eggplant are shortly explained; then the beneficial phytochemicals, antioxidant activity and health effects of eggplant are discussed in detail.

A central support system can facilitate implementation and sustainability of a Classroom-based Undergraduate Research Experience (CURE) in Genomics.

In their 2012 report, the President's Council of Advisors on Science and Technology advocated "replacing standard science laboratory courses with discovery-based research courses"-a challenging proposition that presents practical and pedagogical difficulties. In this paper, we describe our collective experiences working with the Genomics Education Partnership, a nationwide faculty consortium that aims to provide undergraduates with a research experience in genomics through a scheduled course (a classroom-based undergraduate research experience, or CURE). We examine the common barriers encountered in implementing a CURE, program elements of most value to faculty, ways in which a shared core support system can help, and the incentives for and rewards of establishing a CURE on our diverse campuses. While some of the barriers and rewards are specific to a research project utilizing a genomics approach, other lessons learned should be broadly applicable. We find that a central system that supports a shared investigation can mitigate some shortfalls in campus infrastructure (such as time for new curriculum development, availability of IT services) and provides collegial support for change. Our findings should be useful for designing similar supportive programs to facilitate change in the way we teach science for undergraduates.

A course-based research experience: how benefits change with increased investment in instructional time.

There is widespread agreement that science, technology, engineering, and mathematics programs should provide undergraduates with research experience. Practical issues and limited resources, however, make this a challenge. We have developed a bioinformatics project that provides a course-based research experience for students at a diverse group of schools and offers the opportunity to tailor this experience to local curriculum and institution-specific student needs. We assessed both attitude and knowledge gains, looking for insights into how students respond given this wide range of curricular and institutional variables. While different approaches all appear to result in learning gains, we find that a significant investment of course time is required to enable students to show gains commensurate to a summer research experience. An alumni survey revealed that time spent on a research project is also a significant factor in the value former students assign to the experience one or more years later. We conclude: 1) implementation of a bioinformatics project within the biology curriculum provides a mechanism for successfully engaging large numbers of students in undergraduate research; 2) benefits to students are achievable at a wide variety of academic institutions; and 3) successful implementation of course-based research experiences requires significant investment of instructional time for students to gain full benefit.

Comparative genome analyses of Arabidopsis spp.: inferring chromosomal rearrangement events in the evolutionary history of A. thaliana.

Comparative genome analysis is a powerful tool that can facilitate the reconstruction of the evolutionary history of the genomes of modern-day species. The model plant Arabidopsis thaliana with its n = 5 genome is thought to be derived from an ancestral n = 8 genome. Pairwise comparative genome analyses of A. thaliana with polyploid and diploid Brassicaceae species have suggested that rapid genome evolution, manifested by chromosomal rearrangements and duplications, characterizes the polyploid, but not the diploid, lineages of this family. In this study, we constructed a low-density genetic linkage map of Arabidopsis lyrata ssp. lyrata (A. l. lyrata; n = 8, diploid), the closest known relative of A. thaliana (MRCA approximately 5 Mya), using A. thaliana-specific markers that resolve into the expected eight linkage groups. We then performed comparative Bayesian analyses using raw mapping data from this study and from a Capsella study to infer the number and nature of rearrangements that distinguish the n = 8 genomes of A. l. lyrata and Capsella from the n = 5 genome of A. thaliana. We conclude that there is strong statistical support in favor of the parsimony scenarios of 10 major chromosomal rearrangements separating these n = 8 genomes from A. thaliana. These chromosomal rearrangement events contribute to a rate of chromosomal evolution higher than previously reported in this lineage. We infer that at least seven of these events, common to both sets of data, are responsible for the change in karyotype and underlie genome reduction in A. thaliana.