Spatiotemporal Identification of Cell Divisions Using Symmetry Properties in Time-Lapse Phase Contrast Microscopy

A variety of biological and pharmaceutical studies, such as for anti-cancer drugs, require the quantification of cell responses over long periods of time. This is performed with time-lapse video microscopy that gives a long sequence of frames. For this purpose, phase contrast imaging is commonly used since it is minimally invasive. The cell responses of interest in this study are the mitotic cell divisions. Their manual measurements are tedious, subjective, and restrictive. This study introduces an automated method for these measurements. The method starts with preprocessing for restoration and reconstruction of the phase contrast time-lapse sequences. The data are first restored from intensity non-uniformities. Subsequently, the circular symmetry of the contour of the mitotic cells in phase contrast images is used by applying a Circle Hough Transform (CHT) to reconstruct the entire cells. The CHT is also enhanced with the ability to “vote” exclusively towards the center of curvature. The CHT image sequence is then registered for misplacements between successive frames. The sequence is subsequently processed to detect cell centroids in individual frames and use them as starting points to form spatiotemporal trajectories of cells along the positive as well as along the negative time directions, that is, anti-causally. The connectivities of different trajectories enhanced by the symmetry of the trajectories of the daughter cells provide as topological by-products the events of cell divisions together with the corresponding entries into mitoses as well as exits from cytokineses. The experiments use several experimental video sequences from three different cell lines with many cells undergoing mitoses and divisions. The quantitative validations of the results of the processing demonstrate the high performance and efficiency of the method

The Consequentialist Scale: Translation and empirical investigation in a Greek sample

The Consequentialist Scale (Robinson, 2012) [89] assesses the endorsement of consequentialist and deontological moral beliefs. This study empirically investigated the application of the Greek translation of the Consequentialist Scale in a sample of native Greek speakers. Specifically, 415 native Greek speakers completed the questionnaire. To uncover the underlying structure of the 10 items in the Consequentialist Scale, an Exploratory Factor Analysis (EFA) was conducted. The results revealed a three-factor solution, where the deontology factor exhibited the same structure as the original work by Robinson (2012) [89], while the original consequentialism factor split into two separate factors. Significant Pearson's r correlations were observed between age and responses to the Consequentialist Scale. Separate EFAs were conducted for two age groups based on a medial split: younger (36 years old or less) and older (more than 36 years old). Interestingly, the younger group exhibited a two-factor solution with the same structure as the original work, while the older group showed a three-factor solution. A hierarchical k-means cluster analysis revealed that the cluster of participants who scored higher in deontology compared to consequentialism primarily consisted of older participants, whereas the two other clusters comprised of younger participants exhibited the reverse pattern. Neither gender nor previous experience with philosophy significantly affected scores on the Consequentialist Scale. Overall, our study provides evidence that the Consequentialist Scale is suitable for use in the Greek population

Spatiotemporal Identification of Cell Divisions Using Symmetry Properties in Time-Lapse Phase Contrast Microscopy

A variety of biological and pharmaceutical studies, such as for anti-cancer drugs, require the quantification of cell responses over long periods of time. This is performed with time-lapse video microscopy that gives a long sequence of frames. For this purpose, phase contrast imaging is commonly used since it is minimally invasive. The cell responses of interest in this study are the mitotic cell divisions. Their manual measurements are tedious, subjective, and restrictive. This study introduces an automated method for these measurements. The method starts with preprocessing for restoration and reconstruction of the phase contrast time-lapse sequences. The data are first restored from intensity non-uniformities. Subsequently, the circular symmetry of the contour of the mitotic cells in phase contrast images is used by applying a Circle Hough Transform (CHT) to reconstruct the entire cells. The CHT is also enhanced with the ability to “vote” exclusively towards the center of curvature. The CHT image sequence is then registered for misplacements between successive frames. The sequence is subsequently processed to detect cell centroids in individual frames and use them as starting points to form spatiotemporal trajectories of cells along the positive as well as along the negative time directions, that is, anti-causally. The connectivities of different trajectories enhanced by the symmetry of the trajectories of the daughter cells provide as topological by-products the events of cell divisions together with the corresponding entries into mitoses as well as exits from cytokineses. The experiments use several experimental video sequences from three different cell lines with many cells undergoing mitoses and divisions. The quantitative validations of the results of the processing demonstrate the high performance and efficiency of the method

The Consequentialist Scale: Translation and empirical investigation in a Greek sample

The Consequentialist Scale (Robinson, 2012) [89] assesses the endorsement of consequentialist and deontological moral beliefs. This study empirically investigated the application of the Greek translation of the Consequentialist Scale in a sample of native Greek speakers. Specifically, 415 native Greek speakers completed the questionnaire. To uncover the underlying structure of the 10 items in the Consequentialist Scale, an Exploratory Factor Analysis (EFA) was conducted. The results revealed a three-factor solution, where the deontology factor exhibited the same structure as the original work by Robinson (2012) [89], while the original consequentialism factor split into two separate factors. Significant Pearson's r correlations were observed between age and responses to the Consequentialist Scale. Separate EFAs were conducted for two age groups based on a medial split: younger (36 years old or less) and older (more than 36 years old). Interestingly, the younger group exhibited a two-factor solution with the same structure as the original work, while the older group showed a three-factor solution. A hierarchical k-means cluster analysis revealed that the cluster of participants who scored higher in deontology compared to consequentialism primarily consisted of older participants, whereas the two other clusters comprised of younger participants exhibited the reverse pattern. Neither gender nor previous experience with philosophy significantly affected scores on the Consequentialist Scale. Overall, our study provides evidence that the Consequentialist Scale is suitable for use in the Greek population

The Consequentialist Scale: Translation and empirical investigation in a Greek sample

The Consequentialist Scale (Robinson, 2012) [89] assesses the endorsement of consequentialist and deontological moral beliefs. This study empirically investigated the application of the Greek translation of the Consequentialist Scale in a sample of native Greek speakers. Specifically, 415 native Greek speakers completed the questionnaire. To uncover the underlying structure of the 10 items in the Consequentialist Scale, an Exploratory Factor Analysis (EFA) was conducted. The results revealed a three-factor solution, where the deontology factor exhibited the same structure as the original work by Robinson (2012) [89], while the original consequentialism factor split into two separate factors. Significant Pearson's r correlations were observed between age and responses to the Consequentialist Scale. Separate EFAs were conducted for two age groups based on a medial split: younger (36 years old or less) and older (more than 36 years old). Interestingly, the younger group exhibited a two-factor solution with the same structure as the original work, while the older group showed a three-factor solution. A hierarchical k-means cluster analysis revealed that the cluster of participants who scored higher in deontology compared to consequentialism primarily consisted of older participants, whereas the two other clusters comprised of younger participants exhibited the reverse pattern. Neither gender nor previous experience with philosophy significantly affected scores on the Consequentialist Scale. Overall, our study provides evidence that the Consequentialist Scale is suitable for use in the Greek population

C5aR agonist enhances phagocytosis of fibrillar and non-fibrillar Aβ amyloid and preserves memory in a mouse model of familial Alzheimer's disease.

According to the amyloid hypothesis of Alzheimer's disease (AD) the deposition of prefibrillar and fibrillar Aβ peptide sets off the pathogenic cascades of neuroinflammation and neurodegeneration that lead to synaptic and neuronal loss resulting in cognitive decline. Various approaches to reduce amyloid load by reducing production of the Aβ peptide or enhancing amyloid clearance by primary or secondary immunization have not proven successful in clinical trials. Interfering with the normal function of secretases and suboptimal timing of Aβ peptide removal have been put forward as possible explanations. Complement, an innate component of the immune system, has been found to modulate disease pathology and in particular neuronal loss in the AD mouse model but its mechanism of action is complex. C1Q has been shown to facilitate phagocytosis of Aβ peptide but its Ablation attenuates neuroinflammation. Experiments in AD mouse models show that inhibition of complement component C5a reduces amyloid deposition and alleviates neuroinflammation. Phagocytes including microglia, monocytes and neutrophils carry C5a receptors. Here, a widely used mouse model of AD, 5XFAD, was intermittently treated with the oral C5a receptor agonist EP67 and several neuronal and neuroinflammatory markers as well as memory function were assessed. EP67 treatment enhanced phagocytosis, resulting in a significant reduction of both fibrillar and non-fibrillar Aβ, reduced astrocytosis and preserved synaptic and neuronal markers as well as memory function. Timely and phasic recruitment of the innate immune system offers a new therapeutic avenue of treating pre-symptomatic Alzheimer disease

PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European Ancestry.

BACKGROUND: Higher lipoprotein-associated phospholipase A(2)(Lp-PLA2) activity is associated with increased risk of coronary heart disease (CHD), making Lp-PLA2 a potential therapeutic target. PLA2G7 variants associated with Lp-PLA2 activity could evaluate whether this relationship is causal. METHODS AND RESULTS: A meta-analysis including a total of 12 studies (5 prospective, 4 case-control, 1 case-only, and 2 cross-sectional studies; n=26 118) was undertaken to examine the association of the following: (1) Lp-PLA2 activity versus cardiovascular biomarkers and risk factors and CHD events (2 prospective studies; n=4884); (2) PLA2G7 single-nucleotide polymorphisms and Lp-PLA2 activity (3 prospective, 2 case-control, 2 cross-sectional studies; up to n=6094); and (3) PLA2G7 single-nucleotide polymorphisms and angiographic coronary artery disease (2 case-control, 1 case-only study; n=4971 cases) and CHD events (5 prospective, 2 case-control studies; n=5523). Lp-PLA2 activity correlated with several CHD risk markers. Hazard ratios for CHD events for the top versus bottom quartile of Lp-PLA2 activity were 1.61 (95% confidence interval, 1.31 to 1.99) and 1.17 (95% confidence interval, 0.91 to 1.51) after adjustment for baseline traits. Of 7 single-nucleotide polymorphisms, rs1051931 (A379V) showed the strongest association with Lp-PLA2 activity, with VV subjects having 7.2% higher activity than AAs. Genotype was not associated with risk markers, angiographic coronary disease (odds ratio, 1.03; 95% confidence interval, 0.80 to 1.32), or CHD events (odds ratio, 0.98; 95% confidence interval, 0.82 to 1.17). CONCLUSIONS: Unlike Lp-PLA2 activity, PLA2G7 variants associated with modest effects on Lp-PLA2 activity were not associated with cardiovascular risk markers, coronary atheroma, or CHD. Larger association studies, identification of single-nucleotide polymorphisms with larger effects, or randomized trials of specific Lp-PLA2 inhibitors are needed to confirm or refute a contributory role for Lp-PLA2 in CHD