An evolutionary consequence of uniparentally transmitted symbiosis is degradation of symbiont genomes. We use the system of aphids and their maternally inherited obligate endosymbiont, Buchnera ...aphidicola, to explore the evolutionary process of genome degradation. We compared complete genome sequences for 39 Buchnera strains, including 23 newly sequenced symbiont genomes from diverse aphid hosts. We reconstructed the genome of the most recent shared Buchnera ancestor, which contained 616 protein-coding genes, and 39 RNA genes. The extent of subsequent gene loss varied across lineages, resulting in modern genomes ranging from 412 to 646 kb and containing 354-587 protein-coding genes. Loss events were highly nonrandom across loci. Genes involved in replication, transcription, translation, and amino acid biosynthesis are largely retained, whereas genes underlying ornithine biosynthesis, stress responses, and transcriptional regulation were lost repeatedly. Aside from losses, gene order is almost completely stable. The main exceptions involve movement between plasmid and chromosome locations of genes underlying tryptophan and leucine biosynthesis and supporting nutrition of aphid hosts. This set of complete genomes enabled tests for signatures of positive diversifying selection. Of 371 Buchnera genes tested, 29 genes show strong support for ongoing positive selection. These include genes encoding outer membrane porins that are expected to be involved in direct interactions with hosts. Collectively, these results indicate that extensive genome reduction occurred in the ancestral Buchnera prior to aphid diversification and that reduction has continued since, with losses greater in some lineages and for some loci.
Adaptive capacity indicates the capacity to cope with and adapt to a disturbance in a complex social-ecological system. Cultural landscapes can be understood as such systems that are confronted with ...land abandonment and agricultural intensification as key disturbances. However, responses to such cultural landscape loss have not been systematically investigated so far in terms of adaptive capacity. Taking this gap as a starting point and following a context-sensitive approach, this study addresses the question: how can the adaptive capacity of cultural landscape systems for a disturbance such as land abandonment be understood? We answer this question through a comparative case study of four landcare associations in Germany. A conceptual framework that distinguishes between coping and adaptation responses and allows for the analysis of different levels of fit of responses is used. Management of abandoned agricultural land, the establishment of cultural landscape features, provision of consultation and mediation services, and machinery are implemented as coping responses by the four associations. Adaptation responses include the organization of events, public relations work, education, regional brand promotion, lobbying work, and the promotion of regional products. The interactions between the responses that have either synergetic or counterproductive effects were identified. The results of this study emphasize the fit between different responses as an important factor for understanding the adaptive capacity of cultural landscape systems in addition to investing in coping and adaptation responses in isolation. In this sense, adaptive capacity needs to be understood not only in terms of coping (short-term adaptive capacity) and adaptation responses (longer-term adaptive capacity) but also through a good fit, which reduces trade-offs between responses and thus offers a broader range of future options. We conclude by calling for a holistic analysis of different responses to a disturbance that takes account of their fit.
Abstract
Genome structural variations, including duplications, deletions, insertions, and inversions, are central in the evolution of eukaryotic genomes. However, structural variations present ...challenges for high-quality genome assembly, hampering efforts to understand the evolution of gene families and genome architecture. An example is the genome of the pea aphid (Acyrthosiphon pisum) for which the current assembly is composed of thousands of short scaffolds, many of which are known to be misassembled. Here, we present an improved version of the A. pisum genome based on the use of two long-range proximity ligation methods. The new assembly contains four long scaffolds (40–170 Mb), corresponding to the three autosomes and the X chromosome of A. pisum, and encompassing 86% of the new assembly. Assembly accuracy is supported by several quality assessments. Using this assembly, we identify the chromosomal locations and relative ages of duplication events, and the locations of horizontally acquired genes. The improved assembly illuminates the mode of gene family evolution by providing proximity information between paralogs. By estimating nucleotide polymorphism and coverage depth from resequencing data, we determined that many short scaffolds not assembling to chromosomes represent hemizygous regions, which are especially frequent on the highly repetitive X chromosome. Aligning the X-linked aphicarus region, responsible for male wing dimorphism, to the new assembly revealed a 50-kb deletion that cosegregates with the winged male phenotype in some clones. These results show that long-range scaffolding methods can substantially improve assemblies of repetitive genomes and facilitate study of gene family evolution and structural variation.
Quantification of cerebral white matter hyperintensities (WMH) of presumed vascular origin is of key importance in many neurological research studies. Currently, measurements are often still obtained ...from manual segmentations on brain MR images, which is a laborious procedure. The automatic WMH segmentation methods exist, but a standardized comparison of the performance of such methods is lacking. We organized a scientific challenge, in which developers could evaluate their methods on a standardized multi-center/-scanner image dataset, giving an objective comparison: the WMH Segmentation Challenge. Sixty T1 + FLAIR images from three MR scanners were released with the manual WMH segmentations for training. A test set of 110 images from five MR scanners was used for evaluation. The segmentation methods had to be containerized and submitted to the challenge organizers. Five evaluation metrics were used to rank the methods: 1) Dice similarity coefficient; 2) modified Hausdorff distance (95th percentile); 3) absolute log-transformed volume difference; 4) sensitivity for detecting individual lesions; and 5) F1-score for individual lesions. In addition, the methods were ranked on their inter-scanner robustness; 20 participants submitted their methods for evaluation. This paper provides a detailed analysis of the results. In brief, there is a cluster of four methods that rank significantly better than the other methods, with one clear winner. The inter-scanner robustness ranking shows that not all the methods generalize to unseen scanners. The challenge remains open for future submissions and provides a public platform for method evaluation.
Highlights • Radiomics is defined as the use of automated or semi-automated post-processing and analysis of large amounts of quantitative imaging features that can be derived from medical images. • ...The automated generation of these analytical features helps to quantify a number of variables in the imaging assessment of lung malignancy. • We aimed to summarize the current state of the art on this amazingly interesting topic.
Electrical stimulation (ES) has long been used as an alternative clinical treatment and an effective approach to modulate cellular behaviours. In this work we investigated the effects of ES on human ...skin fibroblast activity, myofibroblast transdifferentiation and the consequence on wound healing. Normal human fibroblasts were seeded on heparin-bioactivated PPy/PLLA conductive membranes, cultured for 24 h, and then exposed to ES of 50 or 200 mV/mm for 2, 4, or 6 h. Following ES, the cells were either subjected to various analyses or re-seeded to investigate their healing capacity. Our findings show that ES had no cytotoxic effect on the fibroblasts, as demonstrated by the similar LDH activity levels in the ES-exposed and non-exposed cultures, and by the comparable cell viability under both conditions. Furthermore, the number of viable fibroblasts was higher following exposure to 6 h of ES than in the non-exposed culture. This enhanced cell growth was likely due to the ES up-regulated secretion of FGF-1 and FGF-2. In an in vitro scratch-wound assay where cell monolayer was used as a healing model, the electrically stimulated dermal fibroblasts migrated faster following exposure to ES and recorded a high contractile behaviour toward the collagen gel matrix. This enhanced contraction was supported by the high level of α-smooth muscle actin expressed by the fibroblasts following exposure to ES, indicating the characteristics of myofibroblasts. Remarkably, the modulation of fibroblast growth continued long after ES. In conclusion, this work demonstrates for the first time that exposure to ES promoted skin fibroblast growth and migration, increased growth factor secretion, and promoted fibroblast to myofibroblast transdifferentiation, thus promoting wound healing.
Growing evidence suggests that the efficacy of immunotherapy in non-small cell lung cancers (NSCLCs) is associated with the immune microenvironment within the tumor. We aimed to explore radiologic ...phenotyping using a radiomics approach to assess the immune microenvironment in NSCLC. Two independent NSCLC cohorts (training and test sets) were included. Single-sample gene set enrichment analysis was used to determine the tumor microenvironment, where type 1 helper T (Th1) cells, type 2 helper T (Th2) cells, and cytotoxic T cells were the targets for prediction with computed tomographic (CT) radiomic features. Multiple algorithms were in the modeling followed by final model selection. The training dataset comprised 89 NSCLCs and the test set included 60 cases of lung squamous cell carcinoma and adenocarcinoma. A total of 239 CT radiomic features were used. A linear discriminant analysis model was selected for the final model of Th2 cell group prediction. The area under the curve value of the final model on the test set was 0.684. Predictors of the linear discriminant analysis model were skewness (total and outer pixels), kurtosis, variance (subsampled from delta subtraction inner pixels from outer pixels), and informational measure of correlation. The performances of radiomics on test set of Th1 and cytotoxic T cell were not accurate enough to be predictable. A radiomics approach can be used to interrogate an entire tumor in a noninvasive manner and provide added diagnostic value to identify the immune microenvironment of NSCLC, in particular, Th2 cell signatures.
Plus, minus, and double-strand RNA viruses are all found in nature. We use computational models to study the relative success of these strategies. We consider translation, replication, and virion ...assembly inside one cell, and transmission of virions between cells. For viruses which do not incorporate a polymerase in the capsid, transmission of only plus strands is the default strategy because virions containing minus strands are not infectious. Packaging only plus strands has a significant advantage if the number of RNA strands produced per cell is larger than the number of capsids. In this case, by not packaging minus strands, the virus produces more plus-strand virions. Therefore, plus-strand viruses are selected at low multiplicity of infection. However, at high multiplicity of infection, it is preferable to package both strands because the additional minus virions produced are helpful when there are multiple infections per cell. The fact that plus-strand viruses are widespread while viruses that package both strands are not seen in nature suggests that RNA strands are indeed produced in excess over capsids, and that the multiplicity of infection is not sufficiently high to favor the production of both kinds of virions. For double-strand viruses, we show that it is advantageous to produce only plus strands from the double strand within the cell, as is observed in real viruses. The reason for the success of minus-strand viruses is more puzzling initially. For viruses that incorporate a polymerase in the virion, minus virions are infectious. However, this is not sufficient to explain the success of minus-strand viruses, because in this case, viruses that package both strands outcompete those that package only minus or only plus. Real minus-strand viruses make use of replicable strands that are coated by a nucleoprotein, and separate translatable plus strands that are uncoated. Here we show that when there are distinct replicable and translatable strands, minus-strand viruses are selected.
Grading of gliomas is critical information related to prognosis and survival. We aimed to apply a radiomics approach using various machine learning classifiers to determine the glioma grading.
We ...considered 285 (high grade
= 210, low grade
= 75) cases obtained from the Brain Tumor Segmentation 2017 Challenge. Manual annotations of enhancing tumors, non-enhancing tumors, necrosis, and edema were provided by the database. Each case was multi-modal with T1-weighted, T1-contrast enhanced, T2-weighted, and FLAIR images. A five-fold cross validation was adopted to separate the training and test data. A total of 468 radiomics features were calculated for three types of regions of interest. The minimum redundancy maximum relevance algorithm was used to select features useful for classifying glioma grades in the training cohort. The selected features were used to build three classifier models of logistics, support vector machines, and random forest classifiers. The classification performance of the models was measured in the training cohort using accuracy, sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic curve. The trained classifier models were applied to the test cohort.
Five significant features were selected for the machine learning classifiers and the three classifiers showed an average AUC of 0.9400 for training cohorts and 0.9030 (logistic regression 0.9010, support vector machine 0.8866, and random forest 0.9213) for test cohorts.
Glioma grading could be accurately determined using machine learning and feature selection techniques in conjunction with a radiomics approach. The results of our study might contribute to high-throughput computer aided diagnosis system for gliomas.
The preprocessing of functional magnetic resonance imaging (fMRI) data is necessary to remove unwanted artifacts and transform the data into a standard format. There are several neuroimaging data ...processing tools that are widely used, such as SPM, AFNI, FSL, FreeSurfer, Workbench, and fMRIPrep. Different data preprocessing pipelines yield differing results, which might reduce the reproducibility of neuroimaging studies. Here, we developed a preprocessing pipeline for T1-weighted structural MRI and fMRI data by combining components of well-known software packages to fully incorporate recent developments in MRI preprocessing into a single coherent software package. The developed software, called FuNP (Fusion of Neuroimaging Preprocessing) pipelines, is fully automatic and provides both volume- and surface-based preprocessing pipelines with a user-friendly graphical interface. The reliability of the software was assessed by comparing resting-state networks (RSNs) obtained using FuNP with pre-defined RSNs using open research data (
= 90). The obtained RSNs were well-matched with the pre-defined RSNs, suggesting that the pipelines in FuNP are reliable. In addition, image quality metrics (IQMs) were calculated from the results of three different software packages (i.e., FuNP, FSL, and fMRIPrep) to compare the quality of the preprocessed data. We found that our FuNP outperformed other software in terms of temporal characteristics and artifacts removal. We validated our pipeline with independent local data (
= 28) in terms of IQMs. The IQMs of our local data were similar to those obtained from the open research data. The codes for FuNP are available online to help researchers.
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