Elaboration of bilateral symmetry across Knautia macedonica capitula related to changes in ventral petal expression of CYCLOIDEA-like genes

Abstract Background Shifts in floral form across angiosperms, particularly from radially symmetrical to bilaterally symmetrical flowers, are often associated with shifts in speciation rates and changes in pollination syndrome. Growing evidence across both rosids and asterids indicates that CYCLOIDEA (CYC)-like transcription factors from the TCP gene family play a role in establishing the dorsoventral pattern of flower symmetry, which affects the development of both the corolla and androecium. Previous studies of CYC-like genes, especially of the CYC2 clade, indicate that these genes are dorsally restricted in bilaterally symmetrical flowers. Also, gene duplication of CYC-like genes often correlates with shifts in floral form in both individual flowers and head-like inflorescences (capitula). Results Here, we compared the expression patterns of six CYC-like genes from dorsal, lateral, and ventral petals of internal and external florets across capitula of Knautia macedonica (Dipsacaceae). We demonstrate that multiple copies of CYC-like genes are differentially expressed among petal types and between internal and external florets. Across paralogs, there was a general trend toward a reduction in dorsal expression and an increase in ventral expression in internal florets compared to external florets. However, it was in the ventral petals where a statistically significant increase in expression correlates with a less zygomorphic flower. We also show for the first time lateral-specific expression of a CYC-like gene. Additionally, dorsoventral asymmetric expression of a CYC3 paralog indicates that this understudied gene clade is likely also involved in floral symmetry. Conclusions These data indicate that the elaboration of bilateral symmetry may be regulated by the dorsoventral gradient of expression, with statistically significant changes in ventral expression correlating with changes in dorsoventral morphological specialization

Major perioperative morbidity does not affect long-term survival in patients undergoing esophagectomy for cancer of the esophagus or gastroesophageal junction.

INTRODUCTION: The incidence of cancer of the esophagus/GE junction is dramatically increasing but continues to have a dismal prognosis. Esophagectomy provides the best opportunity for long-term cure but is hampered by increased rates of perioperative morbidity. We reviewed our large institutional experience to evaluate the impact of postoperative complications on the long-term survival of patients undergoing resection for curative intent. METHODS: We identified 237 patients who underwent esophagogastrectomy, with curative intent, for cancer between 1994 and 2008. Complications were graded using the previously published Clavien scale. Survival was calculated using Kaplan-Meier methodology and survival curves were compared using log-rank tests. Multivariate analysis was performed with continuous and categorical variables as predictors of survival, and examined with logistic regression and odds ratio confidence intervals. RESULTS: There were 12 (5 %) perioperative deaths. The average age of all patients was 62 years, and the majority (82 %) was male. Complication grade did not significantly affect long-term survival, although patients with grade IV (serious) complications did have a decreased survival (p = 0.15). Predictors of survival showed that the minimally invasive type esophagectomy (p = 0.0004) and pathologic stage (p = 0.0007) were determining factors. There was a significant difference in overall survival among patients who experienced pneumonia (p = 0.00016) and respiratory complications (p = 0.0004), but this was not significant on multivariate analysis. CONCLUSIONS: In this single-institution series, we found that major perioperative morbidity did not have a negative impact on long-term survival which is different than previous series. The impact of tumor characteristics at time of resection on long-term survival is of most importance

The Causal Effect of Vitamin D Binding Protein (DBP) Levels on Calcemic and Cardiometabolic Diseases: A Mendelian Randomization Study

Background: Observational studies have shown that vitamin D binding protein (DBP) levels, a key determinant of 25-hydroxy- vitamin D (25OHD) levels, and 25OHD levels themselves both associate with risk of disease. If 25OHD levels have a causal influence on disease, and DBP lies in this causal pathway, then DBP levels should likewise be causally associated with disease. We undertook a Mendelian randomization study to determine whether DBP levels have causal effects on common calcemic and cardiometabolic disease. Methods and Findings: We measured DBP and 25OHD levels in 2,254 individuals, followed for up to 10 y, in the Canadian Multicentre Osteoporosis Study (CaMos). Using the single nucleotide polymorphism rs2282679 as an instrumental variable, we applied Mendelian randomization methods to determine the causal effect of DBP on calcemic (osteoporosis and hyperparathyroidism) and cardiometabolic diseases (hypertension, type 2 diabetes, coronary artery disease, and stroke) and related traits, first in CaMos and then in large-scale genome-wide association study consortia. The effect allele was associated with an age-and sex-adjusted decrease in DBP level of 27.4 mg/l (95% CI 24.7, 30.0; n=2,254). DBP had a strong observational and causal association with 25OHD levels (p=3.2x10(-19)). While DBP levels were observationally associated with calcium and body mass index (BMI),these associations were not supported by causal analyses. Despite well-powered sample sizes from consortia, there were no associations of rs2282679 with any other traits and diseases: fasting glucose (0.00 mmol/l [95% CI -0.01, 0.01]; p=1.00; n=46,186); fasting insulin (0.01 pmol/l [95% CI -0.00, 0.01,] ;p=0.22; n=46,186); BMI (0.00 kg/m(2) [95% CI -0.01, 0.01]; p=0.80; n=127,587); bone mineral density (0.01 g/cm(2) [95% CI -0.01, 0.03]; p=0.36; n=32,961); mean arterial pressure (-0.06 mm Hg [95% CI -0.19, 0.07]); p=0.36; n=28,775); ischemic stroke (odds ratio [OR] = 1.00 [95% CI 0.97, 1.04]; p=0.92; n=12, 389/62, 004 cases/controls); coronary artery disease (OR = 1.02 [95% CI 0.99, 1.05]; p=0.31; n=2,233/64, 762); or type 2 diabetes (OR = 1.01 [95% CI 0.97, 1.05]; p=0.76; n=9, 580/53, 810). Conclusions: DBP has no demonstrable causal effect on any of the diseases or traits investigated here, except 25OHD levels. It remains to be determined whether 25OHD has a causal effect on these outcomes independent of DBP

Phenomenological Implications of Deflected Mirage Mediation: Comparison with Mirage Mediation

We compare the collider phenomenology of mirage mediation and deflected mirage mediation, which are two recently proposed "mixed" supersymmetry breaking scenarios motivated from string compactifications. The scenarios differ in that deflected mirage mediation includes contributions from gauge mediation in addition to the contributions from gravity mediation and anomaly mediation also present in mirage mediation. The threshold effects from gauge mediation can drastically alter the low energy spectrum from that of pure mirage mediation models, resulting in some cases in a squeezed gaugino spectrum and a gluino that is much lighter than other colored superpartners. We provide several benchmark deflected mirage mediation models and construct model lines as a function of the gauge mediation contributions, and discuss their discovery potential at the LHC.Comment: 29 pages, 9 figure

Studying Gaugino Mass Unification at the LHC

We begin a systematic study of how gaugino mass unification can be probed at the CERN Large Hadron Collider (LHC) in a quasi-model independent manner. As a first step in that direction we focus our attention on the theoretically well-motivated mirage pattern of gaugino masses, a one-parameter family of models of which universal (high scale) gaugino masses are a limiting case. We improve on previous methods to define an analytic expression for the metric on signature space and use it to study one-parameter deviations from universality in the gaugino sector, randomizing over other soft supersymmetry-breaking parameters. We put forward three ensembles of observables targeted at the physics of the gaugino sector, allowing for a determination of this non-universality parameter without reconstructing individual mass eigenvalues or the soft supersymmetry-breaking gaugino masses themselves. In this controlled environment we find that approximately 80% of the supersymmetric parameter space would give rise to a model for which our method will detect non-universality in the gaugino mass sector at the 10% level with an integrated luminosity of order 10 inverse femptobarns. We discuss strategies for improving the method and for adding more realism in dealing with the actual experimental circumstances of the LHC

Identification of Potential Therapeutic Drugs for Huntington's Disease using Caenorhabditis elegans

The prolonged time course of Huntington's disease (HD) neurodegeneration increases both the time and cost of testing potential therapeutic compounds in mammalian models. An alternative is to initially assess the efficacy of compounds in invertebrate models, reducing time of testing from months to days.We screened candidate therapeutic compounds that were identified previously in cell culture/animal studies in a C. elegans HD model and found that two FDA approved drugs, lithium chloride and mithramycin, independently and in combination suppressed HD neurotoxicity. Aging is a critical contributor to late onset neurodegenerative diseases. Using a genetic strategy and a novel assay, we demonstrate that lithium chloride and mithramycin remain neuroprotective independent of activity of the forkhead transcription factor DAF-16, which mediates the effects of the insulin-like signaling pathway on aging.These results suggest that pathways involved in polyglutamine-induced degeneration are distinct from specific aging pathways. The assays presented here will be useful for rapid and inexpensive testing of other potential HD drugs and elucidating pathways of drug action. Additionally, the neuroprotection conferred by lithium chloride and mithramycin suggests that these drugs may be useful for polyglutamine disease therapy

Harnessing learning biases is essential for applying social learning in conservation

Social learning can influence how animals respond to anthropogenic changes in the environment, determining whether animals survive novel threats and exploit novel resources or produce maladaptive behaviour and contribute to human-wildlife conflict. Predicting where social learning will occur and manipulating its use are, therefore, important in conservation, but doing so is not straightforward. Learning is an inherently biased process that has been shaped by natural selection to prioritize important information and facilitate its efficient uptake. In this regard, social learning is no different from other learning processes because it too is shaped by perceptual filters, attentional biases and learning constraints that can differ between habitats, species, individuals and contexts. The biases that constrain social learning are not understood well enough to accurately predict whether or not social learning will occur in many situations, which limits the effective use of social learning in conservation practice. Nevertheless, we argue that by tapping into the biases that guide the social transmission of information, the conservation applications of social learning could be improved. We explore the conservation areas where social learning is highly relevant and link them to biases in the cues and contexts that shape social information use. The resulting synthesis highlights many promising areas for collaboration between the fields and stresses the importance of systematic reviews of the evidence surrounding social learning practices.BBSRC David Phillips Fellowship (BB/H021817/1

Is parenting style a predictor of suicide attempts in a representative sample of adolescents?

Background Suicidal ideation and suicide attempts are serious but not rare conditions in adolescents. However, there are several research and practical suicide-prevention initiatives that discuss the possibility of preventing serious self-harm. Profound knowledge about risk and protective factors is therefore necessary. The aim of this study is a) to clarify the role of parenting behavior and parenting styles in adolescents’ suicide attempts and b) to identify other statistically significant and clinically relevant risk and protective factors for suicide attempts in a representative sample of German adolescents. Methods In the years 2007/2008, a representative written survey of N = 44,610 students in the 9th grade of different school types in Germany was conducted. In this survey, the lifetime prevalence of suicide attempts was investigated as well as potential predictors including parenting behavior. A three-step statistical analysis was carried out: I) As basic model, the association between parenting and suicide attempts was explored via binary logistic regression controlled for age and sex. II) The predictive values of 13 additional potential risk/protective factors were analyzed with single binary logistic regression analyses for each predictor alone. Non-significant predictors were excluded in Step III. III) In a multivariate binary logistic regression analysis, all significant predictor variables from Step II and the parenting styles were included after testing for multicollinearity. Results Three parental variables showed a relevant association with suicide attempts in adolescents – (all protective): mother’s warmth and father’s warmth in childhood and mother’s control in adolescence (Step I). In the full model (Step III), Authoritative parenting (protective: OR: .79) and Rejecting-Neglecting parenting (risk: OR: 1.63) were identified as significant predictors (p < .001) for suicidal attempts. Seven further variables were interpreted to be statistically significant and clinically relevant: ADHD, female sex, smoking, Binge Drinking, absenteeism/truancy, migration background, and parental separation events. Conclusions Parenting style does matter. While children of Authoritative parents profit, children of Rejecting-Neglecting parents are put at risk – as we were able to show for suicide attempts in adolescence. Some of the identified risk factors contribute new knowledge and potential areas of intervention for special groups such as migrants or children diagnosed with ADHD

An Integrated Framework for Intersectorality: Nonprofitness and Its Influence on Society and Public Administration Programs

Cross-sector interactions have long occurred in the public delivery of goods, services, and interests. While scholars have often addressed cross-sector interactions using the dimensions of publicness (state) and privateness (market), an intersectoral framework necessitates the understanding and incorporation of nonprofitness to account for the dimensions of nonprofits along the public-private continuum. This article proposes a framework for identifying the dimensions of nonprofits in an intersectoral world and draws on relevant examples to illustrate the presence and influence of nonprofitness. The article then focuses on the future of education in the field of public administration and, in light of the proposed framework, makes and considers recommendations to help educational programs better equip students to appreciate work across sectors

Geometric morphometrics reveals shifts in flower shape symmetry and size following gene knockdown of CYCLOIDEA and ANTHOCYANIDIN SYNTHASE

Peer reviewe