Summary:Purpose: Statistical parametric mapping (SPM) is an image-analysis tool that assesses the statistical significance of cerebral blood flow (CBF) changes on a voxel-by-voxel basis, thereby removing the subjectivity inherent in conventional region-of-interest (ROI) analysis. Our platform of single-photon emission computed tomography (SPECT) ictalinterictal difference imaging in clinical epilepsy has been validated for localizing seizure onset. We extend the tools of SPM by further applying statistical measures for the significance of perfusion changes in individual patients to localize epileptogenic foci in patients with defined temporal lobe epilepsy by using paired scans in this preliminary study.Methods: Twelve patients with pairs of periictal and interictal SPECT scans were analyzed in this comparison study between SPECT difference imaging and SPM difference analysis by using a reference database of paired normal healthy images. These 12 patients possessed seizure foci localized to the mesial temporal lobe as confirmed by surgical outcome and by hippocampal sclerosis on pathology. SPM was used to identify clusters of increased or decreased CBF in each patient in contrast to our control group. Results:The regions having the most significant increased or decreased CBF by SPM analysis were in agreement with regions identified by conventional difference imaging and visual analysis by viewers blinded to the results of the SPM analysis. Differentiated further by time of radiopharmaceutical injection, six of seven patients injected within 100 s of seizure onset displayed hyperperfusion changes localized to the corresponding epileptogenic temporal lobe by both techniques. Among patients receiving injections after 100 s, both techniques showed primarily regions of hypoperfusion, which again were similar between these two methods.Conclusions: The results provide strong evidence supporting SPM difference analysis in assessing regions of significant CBF change from baseline in concordance with our current clinically used technique of SPECT ictal-interictal difference imaging in epilepsy patients. Difference analysis using SPM could serve as a useful diagnostic tool in the evaluation of seizure focus in temporal lobe epilepsy. Key Words: Epilepsy-Periictal SPECT-CBF difference imaging-Statistical parametric mapping (SPM).Single-photon emission computed tomography (SPECT) provides important clinical information measuring regional cerebral blood flow changes in the evaluation of epileptic seizure foci. In general, SPECT has demonstrated hyperperfusion in the epileptogenic region periictally and hypoperfusion interictally. Zubal et al. (1) demonstrated improved localization using SPECT difference imaging, whereby interictal images are subtracted on a voxel-by-voxel basis following co-registration and normalization with ictal images. However, the limitation of this approach as with most others remains its degree of interobserver variability (1-3). Other methods of SPECT interpretation have increased diagnostic yield. Ca...

In 2010, a major scientific milestone was achieved for tree fruit crops: publication of the first draft whole genome sequence (WGS) for apple ( Malus domestica ). This WGS, v1.0, was valuable as the initial reference for sequence information, fine mapping, gene discovery, variant discovery, and tool development. A new, high quality apple WGS, GDDH13 v1.1, was released in 2017 and now serves as the reference genome for apple. Over the past decade, these apple WGSs have had an enormous impact on our understanding of apple biological functioning, trait physiology and inheritance, leading to practical applications for improving this highly valued crop. Causal gene identities for phenotypes of fundamental and practical interest can today be discovered much more rapidly. Genome-wide polymorphisms at high genetic resolution are screened efficiently over hundreds to thousands of individuals with new insights into genetic relationships and pedigrees. High-density genetic maps are constructed efficiently and quantitative trait loci for valuable traits are readily associated with positional candidate genes and/or converted into diagnostic tests for breeders. We understand the species, geographical, and genomic origins of domesticated apple more precisely, as well as its relationship to wild relatives. The WGS has turbo-charged application of these classical research steps to crop improvement and drives innovative methods to achieve more durable, environmentally sound, productive, and consumer-desirable apple production. This review includes examples of basic and practical breakthroughs and challenges in using the apple WGSs. Recommendations for “what’s next” focus on necessary upgrades to the genome sequence data pool, as well as for use of the data, to reach new frontiers in genomics-based scientific understanding of apple.

Background Gibberellins (GAs) can have profound effects on growth and development in higher plants. In contrast to their flowering-promotive role in many well-studied plants, GAs can repress flowering in woody perennial plants such as apple (Malus x domestica Borkh.). Although this effect of GA on flowering is intriguing and has commercial importance, the genetic mechanisms linking GA perception with flowering have not been well described. Results Application of a mixture of bioactive GAs repressed flower formation without significant effect on node number or shoot elongation. Using Illumina-based transcriptional sequence data and a newly available, high-quality apple genome sequence, we generated transcript models for genes expressed in the shoot apex, and estimated their transcriptional response to GA. GA treatment resulted in downregulation of a diversity of genes participating in GA biosynthesis, and strong upregulation of the GA catabolic GA2 OXIDASE genes, consistent with GA feedback and feedforward regulation, respectively. We also observed strong downregulation of numerous genes encoding potential GA transporters and receptors. Additional GA-responsive genes included potential components of cytokinin (CK), abscisic acid (ABA), brassinosteroid, and auxin signaling pathways. Finally, we observed rapid and strong upregulation of both of two copies of a gene previously observed to inhibit flowering in apple, MdTFL1 (TERMINAL FLOWER 1). Conclusion The rapid and robust upregulation of genes associated with GA catabolism in response to exogenous GA, combined with the decreased expression of GA biosynthetic genes, highlights GA feedforward and feedback regulation in the apple shoot apex. The finding that genes with potential roles in GA metabolism, transport and signaling are responsive to GA suggests GA homeostasis may be mediated at multiple levels in these tissues. The observation that TFL1-like genes are induced quickly in response to GA suggests they may be directly targeted by GA-responsive transcription factors, and offers a potential explanation for the flowering-inhibitory effects of GA in apple. These results provide a context for investigating factors that may transduce the GA signal in apple, and contribute to a preliminary genetic framework for the repression of flowering by GAs in a woody perennial plant.

Timing of flowering is a fundamental developmental transition that has great ecological and agricultural importance. For perennial plants, seasonal timing of bloom and anthesis, which is the ultimate stage of flowering, can be determined by the net effect of several preceding developmental steps: seasonal timing of floral initiation, rate and extent of floral development before winter dormancy, duration of dormancy, and rate of floral development after release from dormancy. In the domestic apple (Malus ×domestica), fruit production has generally favored cultivars that bloom relatively early in the season. However, floral tissues are easily damaged by freezing temperatures, and freeze injury is especially problematic in years when abnormally warm temperatures in early spring lead to rapid floral development. To facilitate identification of genes/alleles that govern bloom time, and that could add versatility to production systems for apple, we evaluated seasonal bloom time for accessions of M. ×domestica, wild apple species (Malus sp.), and Malus hybrids maintained in a large germplasm diversity collection.

Hard cider, made by fermenting apple (Malus ×domestica) juice, was at one time the most widely consumed alcoholic beverage in America. Largely abandoned after Prohibition, within the past 2 decades the rise in popularity of craft beverages has led to the reemergence of hard cider as an alternative to beer, wine, and spirits. Today, hard cider represents one of the fastest growing sectors within the craft beverage industry. The recent interest in cider presents additional marketing opportunities for apple growers and businesses currently involved in, or considering entering, the apple cider or craft beverages industries. However, the lack of a strong history or experience in selecting, producing, and using cider apples poses a significant challenge to this emerging market. This article reviews the current state of research in cider apple production, including economic feasibility, mechanized management, and cultivar evaluation and improvement.