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Entomophthoralean fungi are insect pathogenic fungi and are characterized by their active discharge of infective conidia that infect insects. Our aim was to study the effects of temperature on the discharge and to characterize the variation in the associated temporal pattern of a newly discovered Pandora species with focus on peak location and shape of the discharge. Mycelia were incubated at various temperatures in darkness, and conidial discharge was measured over time. We used a novel modification of a statistical model (pavpop), that simultaneously estimates phase and amplitude effects, into a setting of generalized linear models. This model is used to test hypotheses of peak location and discharge of conidia. The statistical analysis showed that high temperature leads to an early and fast decreasing peak, whereas there were no significant differences in total number of discharged conidia. Using the proposed model we also quantified the biological variation in the timing of the peak location at a fixed temperature. [ABSTRACT FROM AUTHOR]

A central task in the analysis of human movement behavior is to determine systematic patterns and differences across experimental conditions, participants and repetitions. This is possible because human movement is highly regular, being constrained by invariance principles. Movement timing and movement path, in particular, are linked through scaling laws. Separating variations of movement timing from the spatial variations of movements is a well-known challenge that is addressed in current approaches only through forms of preprocessing that bias analysis. Here we propose a novel nonlinear mixed-effects model for analyzing temporally continuous signals that contain systematic effects in both timing and path. Identifiability issues of path relative to timing are overcome by using maximum likelihood estimation in which the most likely separation of space and time is chosen given the variation found in data. The model is applied to analyze experimental data of human arm movements in which participants move a hand-held object to a target location while avoiding an obstacle. The model is used to classify movement data according to participant. Comparison to alternative approaches establishes nonlinear mixed-effects models as viable alternatives to conventional analysis frameworks. The model is then combined with a novel factor-analysis model that estimates the low-dimensional subspace within which movements vary when the task demands vary. Our framework enables us to visualize different dimensions of movement variation and to test hypotheses about the effect of obstacle placement and height on the movement path. We demonstrate that the approach can be used to uncover new properties of human movement. [ABSTRACT FROM AUTHOR]

Background: Topoisomerase I (Top1) is the target of Top1 inhibitor chemotherapy. The TOP1 gene, located at 20q12-q13.1, is frequently detected at elevated copy numbers in colorectal cancer (CRC). The present study explores the mechanism, frequency and prognostic impact of TOP1 gene aberrations in stage III CRC and how these can be detected by fluorescent in situ hybridization (FISH). Methods: Nine CRC cell line metaphase spreads were analyzed by FISH with a TOP1 probe in combination with a reference probe covering either the centromeric region of chromosome 20 (CEN-20) or chromosome 2 (CEN-2). Tissue sections from 154 chemonaive stage III CRC patients, previously studied with TOP1/CEN-20, were analyzed with TOP1/CEN-2. Relationships between biomarker status and overall survival (OS), time to recurrence (TTR) in CRC and time to local recurrence (LR; rectal cancer only) were determined. Results: TOP1 aberrations were observed in four cell line metaphases. In all cell lines CEN-2 was found to reflect chromosomal ploidy levels and therefore the TOP1/CEN-2 probe combination was selected to identify TOP1 gene gains (TOP1/CEN-2≥1.5). One hundred and three patients (68.2%) had TOP1 gain, of which 15 patients (14.6%) harbored an amplification (TOP1/CEN-20≥2.0). TOP1 gene gain did not have any association with clinical endpoints, whereas TOP1 amplification showed a non-significant trend towards longer TTR (multivariate HR: 0.50, p = 0.08). Once amplified cases were segregated from other cases of gene gain, non-amplified gene increases (TOP1/CEN-2≥1.5 and TOP1/CEN-20<2.0) showed a trend towards shorter TTR (univariate HR: 1.57, p = 0.07). Conclusions: TOP1 gene copy number increase occurs frequently in stage III CRC in a mechanism that often includes CEN-20. Using CEN-2 as a measurement for tumor ploidy levels, we were able to discriminate between different mechanisms of gene gain, which appeared to differ in prognostic impact. TOP1 FISH guidelines have been updated. [ABSTRACT FROM AUTHOR]

Ascosphaera apis causes chalkbrood in honeybees, a chronic disease that reduces the number of viable offspring in the nest. Although lethal for larvae, the disease normally has relatively low virulence at the colony level. A recent study showed that there is genetic variation for host susceptibility, but whether Ascosphaera apis strains differ in virulence is unknown. We exploited a recently modified in vitro rearing technique to infect honeybee larvae from three colonies with naturally mated queens under strictly controlled laboratory conditions, using four strains from two distinct A. apis clades. We found that both strain and colony of larval origin affected mortality rates. The strains from one clade caused 12-14% mortality while those from the other clade induced 71-92% mortality. Larvae from one colony showed significantly higher susceptibility to chalkbrood infection than larvae from the other two colonies, confirming the existence of genetic variation in susceptibility across colonies. Our results are consistent with antagonistic coevolution between a specialized fungal pathogen and its host, and suggest that beekeeping industries would benefit from more systematic monitoring of this chronic stress factor of their colonies. [ABSTRACT FROM AUTHOR]

Background: Topoisomerase I (Top1) is the target of Top1 inhibitor chemotherapy. The TOP1 gene, located at 20q12-q13.1, is frequently detected at elevated copy numbers in colorectal cancer (CRC). The present study explores the mechanism, frequency and prognostic impact of TOP1 gene aberrations in stage III CRC and how these can be detected by fluorescent in situ hybridization (FISH)., Methods: Nine CRC cell line metaphase spreads were analyzed by FISH with a TOP1 probe in combination with a reference probe covering either the centromeric region of chromosome 20 (CEN-20) or chromosome 2 (CEN-2). Tissue sections from 154 chemonaive stage III CRC patients, previously studied with TOP1/CEN-20, were analyzed with TOP1/CEN-2. Relationships between biomarker status and overall survival (OS), time to recurrence (TTR) in CRC and time to local recurrence (LR; rectal cancer only) were determined., Results: TOP1 aberrations were observed in four cell line metaphases. In all cell lines CEN-2 was found to reflect chromosomal ploidy levels and therefore the TOP1/CEN-2 probe combination was selected to identify TOP1 gene gains (TOP1/CEN-2≥1.5). One hundred and three patients (68.2%) had TOP1 gain, of which 15 patients (14.6%) harbored an amplification (TOP1/CEN-20≥2.0). TOP1 gene gain did not have any association with clinical endpoints, whereas TOP1 amplification showed a non-significant trend towards longer TTR (multivariate HR: 0.50, p = 0.08). Once amplified cases were segregated from other cases of gene gain, non-amplified gene increases (TOP1/CEN-2≥1.5 and TOP1/CEN-20<2.0) showed a trend towards shorter TTR (univariate HR: 1.57, p = 0.07)., Conclusions: TOP1 gene copy number increase occurs frequently in stage III CRC in a mechanism that often includes CEN-20. Using CEN-2 as a measurement for tumor ploidy levels, we were able to discriminate between different mechanisms of gene gain, which appeared to differ in prognostic impact. TOP1 FISH guidelines have been updated.