ABSTRACT
Candida albicans is a leading cause of death due to systemic fungal infections. Poor patient outcomes are attributable to the limited number of antifungal classes and the increasing prevalence of drug resistance. Protein kinases have emerged as rewarding targets in the development of drugs for diverse diseases, yet kinases remain untapped in the quest for new antifungals. Here, we performed a comprehensive analysis of the C. albicans kinome to identify genes for which loss-of-function confers hypersensitivity to the two most widely deployed antifungals, echinocandins and azoles. Through this analysis, we found a role for the casein kinase 1 (CK1) homologue Hrr25 in regulating tolerance to both antifungals as well as target-mediated echinocandin resistance. Follow-up investigations established that Hrr25 regulates these responses through its interaction with the SBF transcription factor. Thus, we provide insights into the circuitry governing cellular responses to antifungals and implicate Hrr25 as a key mediator of drug resistance.
ABSTRACT
Comparative studies of invasive, noninvasive alien, and native congenic plant species can identify plant traits that drive invasiveness. In particular, functional traits associated with rapid growth rate and high fecundity likely facilitate invasive success. As such traits often exhibit high phenotypic plasticity, characterizing plastic responses to anthropogenic environmental changes such as eutrophication and disturbance is important for predicting the invasive success of alien plant species in the future. Here, we compared trait expression and phenotypic plasticity at the species level among invasive, noninvasive alien, and native Bidens species. Plants were grown under nutrient addition and competition treatments, and their functional, morphological, and seed traits were examined. Invasive B. frondosa exhibited higher phenotypic plasticity in most measured traits than did the alien noninvasive B. pilosa or native B. bipinnata. However, differential plastic responses to environmental treatments rarely altered the rank of trait values among the three Bidens species, except for the number of inflorescences. The achene size of B. frondosa was larger, but its pappus length was shorter than that of B. pilosa. Two species demonstrated opposite plastic responses of pappus length to fertilization. These results suggest that the plasticity of functional traits does not significantly contribute to the invasive success of B. frondosa. The dispersal efficiency of B. frondosa is expected to be lower than that of B. pilosa, suggesting that long-distance dispersal is likely not a critical factor in determining invasive success.
ABSTRACT
STUDY DESIGN: A retrospective study. PURPOSE: To evaluate the prevalence and risk factors of asymptomatic cervical or thoracic lesions in elderly patients who have undergone surgery for lumbar spinal stenosis. OVERVIEW OF LITERATURE: Concurrent multiple spinal lesions have been reported in many studies with a varied prevalence, and described the characteristics of the disease and its treatment options. However, the cervical or thoracic lesions without apparent symptoms in patients with symptomatic lumbar stenosis had not been evaluated. METHODS: A total of 101 elderly patients (aged 65 or more), who had undergone surgery for lumbar spinal stenosis from January 2005 to December 2005, were enrolled in this study. All patients underwent lumbar magnetic resonance imaging (MRI) along with T2-weighted cervical and thoracic sagittal MRI prior to surgery. The concurrent cervical or thoracic lesions were classified according to the disease entity, and the severity of the lesions was graded from grade 0 (no lesion) to grade 4 (any lesion compressing the cord with a signal change). The prevalence of concurrent cervical and thoracic lesions was then analyzed. In addition, the risk factors for the development of concurrent lesions were evaluated, and the risk factors affecting the severity of the concurrent lesion were analyzed individually. RESULTS: Seventy-seven (76.2%) and 30 (29.7%) patients had a concurrent cervical and thoracic lesion, respectively. Twenty-six patients (25.7%) had both a cervical and thoracic lesion. There was a positive correlation between the symptom duration of lumbar stenosis and the prevalence of both cervical (p = 0.044) and thoracic (p = 0.022) lesions. CONCLUSIONS: The incidence of asymptomatic cervical or thoracic lesions is apparently high in elderly patients who have undergone surgery for lumbar spinal stenosis, particularly in those with longer symptom duration. This highlights the need for a preoperative evaluation of the cervical and thoracic spine in these patients.
