45 research outputs found

    Fitness of Crop-Wild Hybrid Sunflower under Competitive Conditions: Implications for Crop-to-Wild Introgression

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    Understanding the likelihood and extent of introgression of novel alleles in hybrid zones requires comparison of lifetime fitness of parents and hybrid progeny. However, fitness differences among cross types can vary depending on biotic conditions, thereby influencing introgression patterns. Based on past work, we predicted that increased competition would enhance introgression between cultivated and wild sunflower (Helianthus annuus) by reducing fitness advantages of wild plants. To test this prediction, we established a factorial field experiment in Kansas, USA where we monitored the fitness of four cross types (Wild, F1, F2, and BCw hybrids) under different levels of interspecific and intraspecific competition. Intraspecific manipulations consisted both of density of competitors and of frequency of crop-wild hybrids. We recorded emergence of overwintered seeds, survival to reproduction, and numbers of seeds produced per reproductive plant. We also calculated two compound fitness measures: seeds produced per emerged seedling and seeds produced per planted seed. Cross type and intraspecific competition affected emergence and survival to reproduction, respectively. Further, cross type interacted with competitive treatments to influence all other fitness traits. More intense competition treatments, especially related to density of intraspecific competitors, repeatedly reduced the fitness advantage of wild plants when considering seeds produced per reproductive plant and per emerged seedling, and F2 plants often became indistinguishable from the wilds. Wild fitness remained superior when seedling emergence was also considered as part of fitness, but the fitness of F2 hybrids relative to wild plants more than quadrupled with the addition of interspecific competitors and high densities of intraspecific competitors. Meanwhile, contrary to prediction, lower hybrid frequency reduced wild fitness advantage. These results emphasize the importance of taking a full life cycle perspective. Additionally, due to effects of exogenous selection, a given hybrid generation may be especially well-suited to hastening introgression under particular environmental conditions.The study was conducted at and partially supported by the University of Kansas Field Station, a research unit of the Kansas Biological Survey and the University of Kansas. It was also supported by Biotechnology Risk Assessment Grant Program competitive grant no. 2006-39454-17438 to AAS, KLM, and HMA from the United States Department of Agriculture, National Institute of Food and Agriculture; www.nifa.usda.gov. Salaries and research support also provided by State and Federal funds appropriated to the Ohio Agricultural Research and Development Center, Ohio State University: manuscript no. HCS-14-07. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Data mining MR image features of select structures for lateralization of mesial temporal lobe epilepsy

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    PURPOSE: This study systematically investigates the predictive power of volumetric imaging feature sets extracted from select neuroanatomical sites in lateralizing the epileptogenic focus in mesial temporal lobe epilepsy (mTLE) patients. METHODS: A cohort of 68 unilateral mTLE patients who had achieved an Engel class I outcome postsurgically was studied retrospectively. The volumes of multiple brain structures were extracted from preoperative magnetic resonance (MR) images in each. The MR image data set consisted of 54 patients with imaging evidence for hippocampal sclerosis (HS-P) and 14 patients without (HS-N). Data mining techniques (i.e., feature extraction, feature selection, machine learning classifiers) were applied to provide measures of the relative contributions of structures and their correlations with one another. After removing redundant correlated structures, a minimum set of structures was determined as a marker for mTLE lateralization. RESULTS: Using a logistic regression classifier, the volumes of both hippocampus and amygdala showed correct lateralization rates of 94.1%. This reflected about 11.7% improvement in accuracy relative to using hippocampal volume alone. The addition of thalamic volume increased the lateralization rate to 98.5%. This ternary-structural marker provided a 100% and 92.9% mTLE lateralization accuracy, respectively, for the HS-P and HS-N groups. CONCLUSIONS: The proposed tristructural MR imaging biomarker provides greater lateralization accuracy relative to single- and double-structural biomarkers and thus, may play a more effective role in the surgical decision-making process. Also, lateralization of the patients with insignificant atrophy of hippocampus by the proposed method supports the notion of associated structural changes involving the amygdala and thalamus

    A genetic locus complements resistance to Bordetella pertussis-induced histamine sensitization.

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    Histamine plays pivotal role in normal physiology and dysregulated production of histamine or signaling through histamine receptors (HRH) can promote pathology. Previously, we showed that Bordetella pertussis or pertussis toxin can induce histamine sensitization in laboratory inbred mice and is genetically controlled by Hrh1/HRH1. HRH1 allotypes differ at three amino acid residues with

    JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies

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    BACKGROUND. Monogenic IFN-mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN response gene signature, inflammatory organ damage, and high mortality. We used the JAK inhibitor baricitinib, with IFN-blocking activity in vitro, to ameliorate disease. METHODS. Between October 2011 and February 2017, 10 patients with CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), 4 patients with SAVI (stimulator of IFN genes-associated [STING-associated] vasculopathy with onset in infancy), and 4 patients with other interferonopathies were enrolled in an expanded access program. The patients underwent dose escalation, and the benefit was assessed by reductions in daily disease symptoms and corticosteroid requirement. Quality of life, organ inflammation, changes in IFN-induced biomarkers, and safety were longitudinally assessed. RESULTS. Eighteen patients were treated for a mean duration of 3.0 years (1.5-4.9 years). The median daily symptom score decreased from 1.3 (interquartile range [IQR], 0.93-1.78) to 0.25 (IQR, 0.1-0.63) (P < 0.0001). In 14 patients receiving corticosteroids at baseline, daily prednisone doses decreased from 0.44 mg/kg/day (IQR, 0.31-1.09) to 0.11 mg/kg/day (IQR, 0.02-0.24) (P < 0.01), and 5 of 10 patients with CANDLE achieved lasting clinical remission. The patients' quality of life and height and bone mineral density Z-scores significantly improved, and their IFN biomarkers decreased. Three patients, two of whom had genetically undefined conditions, discontinued treatment because of lack of efficacy, and one CANDLE patient discontinued treatment because of BK viremia and azotemia. The most common adverse events were upper respiratory infections, gastroenteritis, and BK viruria and viremia. CONCLUSION. Upon baricitinib treatment, clinical manifestations and inflammatory and IFN biomarkers improved in patients with the monogenic interferonopathies CANDLE, SAVI, and other interferonopathies. Monitoring safety and efficacy is important in benefit-risk assessment

    Exome-wide Rare Variant Analysis Identifies TUBA4A Mutations Associated with Familial ALS

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    Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an exome-wide rare variant burden analysis of 363 index cases with familial ALS (FALS). The results revealed an excess of patient variants within TUBA4A, the gene encoding the Tubulin, Alpha 4A protein. Analysis of a further 272 FALS cases and 5,510 internal controls confirmed the overrepresentation as statistically significant and replicable. Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability. These results further emphasize the role of cytoskeletal defects in ALS and demonstrate the power of gene-based rare variant analyses in situations where causal genes cannot be identified through traditional segregation analysis

    Data from: Life history traits and phenotypic selection among sunflower crop-wild hybrids and their wild counterpart: implications for crop allele introgression

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    Hybridization produces strong evolutionary forces. In hybrid zones, selection can differentially occur on traits and selection intensities may differ among hybrid generations. Understanding these dynamics in crop-wild hybrid zones can clarify crop-like traits likely to introgress into wild populations and the particular hybrid generations through which introgression proceeds. In a field experiment with four crop-wild hybrid Helianthus annuus (sunflower) cross types, we measured growth and life history traits and performed phenotypic selection analysis on early season traits to ascertain the likelihood, and routes, of crop allele introgression into wild sunflower populations. All cross types overwintered, emerged in the spring, and survived until flowering, indicating no early life history barriers to crop allele introgression. While selection indirectly favored earlier seedling emergence and taller early season seedlings, direct selection only favored greater early season leaf length. Further, there was cross type variation in the intensity of selection operating on leaf length. Thus, introgression of multiple early season crop-like traits, due to direct selection for greater early season leaf length, should not be impeded by any cross type and may proceed at different rates among generations. In sum, alleles underlying early season sunflower crop-like traits are likely to introgress into wild sunflower populations

    Data from: Fitness of crop-wild hybrid sunflowers under competitive conditions: implications for crop-to-wild introgression

    No full text
    Understanding the likelihood and extent of introgression of novel alleles in hybrid zones requires comparison of lifetime fitness of parents and hybrid progeny. However, fitness differences among cross types can vary depending on biotic conditions, thereby influencing introgression patterns. Based on past work, we predicted that increased competition would enhance introgression between cultivated and wild sunflower (Helianthus annuus) by reducing fitness advantages of wild plants. To test this prediction, we established a factorial field experiment in Kansas, USA where we monitored the fitness of four cross types (Wild, F1, F2, and BCw hybrids) under different levels of interspecific and intraspecific competition. Intraspecific manipulations consisted both of density of competitors and of frequency of crop-wild hybrids. We recorded emergence of overwintered seeds, survival to reproduction, and numbers of seeds produced per reproductive plant. We also calculated two compound fitness measures: seeds produced per emerged seedling and seeds produced per planted seed. Cross type and intraspecific competition affected emergence and survival to reproduction, respectively. Further, cross type interacted with competitive treatments to influence all other fitness traits. More intense competition treatments, especially related to density of intraspecific competitors, repeatedly reduced the fitness advantage of wild plants when considering seeds produced per reproductive plant and per emerged seedling, and F2 plants often became indistinguishable from the wilds. Wild fitness remained superior when seedling emergence was also considered as part of fitness, but the fitness of F2 hybrids relative to wild plants more than quadrupled with the addition of interspecific competitors and high densities of intraspecific competitors. Meanwhile, contrary to prediction, lower hybrid frequency reduced wild fitness advantage. These results emphasize the importance of taking a full life cycle perspective. Additionally, due to effects of exogenous selection, a given hybrid generation may be especially well-suited to hastening introgression under particular environmental conditions

    Lateralization of temporal lobe epilepsy by multimodal multinomial hippocampal response-driven models

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    PURPOSE: Multiple modalities are used in determining laterality in mesial temporal lobe epilepsy (mTLE). It is unclear how much different imaging modalities should be weighted in decision-making. The purpose of this study is to develop response-driven multimodal multinomial models for lateralization of epileptogenicity in mTLE patients based upon imaging features in order to maximize the accuracy of noninvasive studies. METHODS AND MATERIALS: The volumes, means and standard deviations of FLAIR intensity and means of normalized ictal-interictal SPECT intensity of the left and right hippocampi were extracted from preoperative images of a retrospective cohort of 45 mTLE patients with Engel class I surgical outcomes, as well as images of a cohort of 20 control, nonepileptic subjects. Using multinomial logistic function regression, the parameters of various univariate and multivariate models were estimated. Based on the Bayesian model averaging (BMA) theorem, response models were developed as compositions of independent univariate models. RESULTS: A BMA model composed of posterior probabilities of univariate response models of hippocampal volumes, means and standard deviations of FLAIR intensity, and means of SPECT intensity with the estimated weighting coefficients of 0.28, 0.32, 0.09, and 0.31, respectively, as well as a multivariate response model incorporating all mentioned attributes, demonstrated complete reliability by achieving a probability of detection of one with no false alarms to establish proper laterality in all mTLE patients. CONCLUSION: The proposed multinomial multivariate response-driven model provides a reliable lateralization of mesial temporal epileptogenicity including those patients who require phase II assessment
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