Distinguishing Healthy Ageing from Dementia: A Biomechanical Simulation of Brain Atrophy Using Deep Networks

Biomechanical modeling of tissue deformation can be used to simulate different scenarios of longitudinal brain evolution. In this work, we present a deep learning framework for hyper-elastic strain modelling of brain atrophy, during healthy ageing and in Alzheimer’s Disease. The framework directly models the effects of age, disease status, and scan interval to regress regional patterns of atrophy, from which a strain-based model estimates deformations. This model is trained and validated using 3D structural magnetic resonance imaging data from the ADNI cohort. Results show that the framework can estimate realistic deformations, following the known course of Alzheimer’s disease, that clearly differentiate between healthy and demented patterns of ageing. This suggests the framework has potential to be incorporated into explainable models of disease, for the exploration of interventions and counterfactual examples

A quantitative image analysis for the cellular cytoskeleton during in vitro tumor growth

The cellular cytoskeleton is a dynamic subcellular structure that can be a marker of key biological phenomena including cell division, organelle movement, shape changes and locomotion during the avascular tumor phase. Little attention is paid to quantify changes in the cytoskeleton while nuclei and cytoplasmic both are present in subcellular microscopic images. In this paper, we proposed a quantitative image analysis method to analyze subcellular cytoskeletal changes using a texture analysis method preceded by segmentation of nuclei, cytoplasm and ruffling regions (area except nuclei and cytoplasm). To test and validate this model we hypothesized that Mammary Serine Protease Inhibitor (maspin) acts as cytoskeleton regulator that mediates cell-extracellular matrix (ECM) adhesion in tumor. Maspin-a tumor suppressor gene shows multiple tumor suppressive properties such as increasing tumor cell apoptosis and reducing migration, proliferation, invasion, and overall tumor metastasis. The proposed method obtained separated ruffling regions from segmentation steps and then adopted gray–level histograms (GLH) and grey-level co-occurrence matrix (GLCM) texture analysis techniques. In order to verify the reliability, the proposed texture analysis method was used to compare the control and maspin expressing cells grown on different ECM components: plastic, collagen I, fibronectin and laminin. The results show that the texture parameters extracted reflect the different cytoskeletal changes. These changes indicate that maspin acts as a regulator of the cell-ECM enhancement process, while it reduces the cell migration. Overall, this paper not only presents a quantitative image analysis approach to analyze subcellular cytoskeletal architectures but also provides a comprehensive tool for the biologist, pathologist, cancer specialist, and computer scientist to understand cellular and subcellular organization of cells. In long term, this method can be extended to be used in live cell tracking in vivo, image informatics based point-of-care expert system and quantification of various complex architectures in organisms

Emergent Prelabor Cesarean Birth in Solid Organ Transplant Recipients: Associated Risk Factors and Outcomes.

BACKGROUND: Pregnancies after solid-organ transplant are at a higher risk for antepartum admission and pregnancy complications, including cesarean birth. Emergent prelabor cesarean is associated with increased maternal and neonatal morbidity in other high-risk populations, but its incidence and impact in transplant recipients is not well understood OBJECTIVE: To characterize the risk factors and outcomes of emergency prelabor cesarean birth in kidney and liver transplant recipients STUDY DESIGN: Retrospective cohort study of all kidney and liver transplant recipients \u3e20 weeks\u27 gestation enrolled in the Transplant Pregnancy Registry International between 1976 and 2019. Participants admitted antepartum who required an emergency prelabor cesarean were compared to those admitted antepartum who underwent non-emergent birth. Primary outcomes were composite severe maternal morbidity and neonatal composite morbidity. Multivariable logistic regression was conducted for neonatal composite morbidity RESULTS: Of 1,979 births, 181 pregnancies (188 neonates) with an antepartum admission were included. 51 pregnancies (53 neonates, 28%) were delivered by emergent prelabor cesarean birth compared with 130 pregnancies (135 neonates, 72%) admitted antepartum who subsequently did not require emergent delivery. The most common indication for emergent delivery was non-reassuring fetal heart tracing (44 neonates, 86%). Pregnant people who underwent an emergent prelabor cesarean were less likely to birth at a transplant center (37.3% vs 41.5%, p=0.04) and had increased rates of chronic hypertension (33.3% vs 16.2%, p=0.02). There was no significant difference in severe maternal morbidity (3.9% vs 4.6%, p=0.84), though there was an increase in surgical site infection in the emergent prelabor cesarean cohort (3.9% vs 0%, p=0.02). Among those with an emergent prelabor cesarean, there was a significant increase in neonatal composite morbidity (43.4% vs 19.3%,

Evidence for the association of the DAOA (G72) gene with schizophrenia and bipolar disorder but not for the association of the DAO gene with schizophrenia

Background: Previous linkage and association studies have implicated the D-amino acid oxidase activator gene (DAOA)/G30 locus or neighbouring region of chromosome 13q33.2 in the genetic susceptibility to both schizophrenia and bipolar disorder. Four single nucleotide polymorphisms (SNPs) within the D-amino acid oxidase (DAO) gene located at 12q24.11 have also been found to show allelic association with schizophrenia.Methods: We used the case control method to test for genetic association with variants at these loci in a sample of 431 patients with schizophrenia, 303 patients with bipolar disorder and 442 ancestrally matched supernormal controls all selected from the UK population.Results: Ten SNPs spanning the DAOA locus were genotyped in these samples. In addition three SNPs were genotyped at the DAO locus in the schizophrenia sample. Allelic association was detected between the marker rs3918342 (M23), 3' to the DAOA gene and both schizophrenia (chi(2) = 5.824 p = 0.016) and bipolar disorder (chi(2) = 4.293 p = 0.038). A trend towards association with schizophrenia was observed for two other DAOA markers rs3916967 (M14, chi(2) = 3.675 p = 0.055) and rs1421292 (M24; chi(2) = 3.499 p = 0.062). A test of association between a three marker haplotype comprising of the SNPs rs778293 (M22), rs3918342 (M23) and rs1421292 (M24) and schizophrenia gave a global empirical significance of p = 0.015. No evidence was found to confirm the association of genetic markers at the DAO gene with schizophrenia.Conclusion: Our results provide some support for a role for DAOA in susceptibility to schizophrenia and bipolar disorder

Following the Formation of Synaptonemal Complex Formation in Wheat and Barley by High-Resolution Microscopy

International audienceWheat and barley have large genomes of 15 Gb and 5.1 Gb, respectively, which is much larger than the human genome (3.3 Gb). The release of their respective genomes has been a tremendous advance the understanding of the genome organization and the ability for deeper functional analysis in particular meiosis. Meiosis is the cell division required during sexual reproduction. One major event of meiosis is called recombination, or the formation of crossing over, a tight link between homologous chromosomes, ensuring gene exchange and faithful chromosome segregation. Recombination is a major driver of genetic diversity but in these large genome crops, the vast majority of these events is constrained at the end of their chromosomes. It is estimated that in barley, about 30% of the genes are located within the poor recombining centromeric regions, making important traits, such as resistance to pest and disease for example, difficult to access. Increasing recombination in these crops has the potential to speed up breeding program and requires a good understand of the meiotic mechanism. However, most research on recombination in plant has been carried in Arabidopsis thaliana which despite many of the advantages it brings for plant research, has a small genome and more spread out of recombination compare to barley or wheat. Advance in microscopy and cytological procedures have emerged in the last few years, allowing to follow meiotic events in these crops. This protocol provides the steps required for cytological preparation of barley and wheat pollen mother cells for light microscopy, highlighting some of the differences between the two cereals

De novo genome assembly of the meadow brown butterfly, Maniola jurtina

This is the final version. Available on open access from the Genetics Society of America via the DOI in this record. Data availability: The raw sequencing data and genome assembly have been deposited at the NCBI SRA database under the BioProject PRJNA498046 and genome accession number VMKL00000000. Blast results, annotation and proteome associated with this manuscript are available at https://zenodo.org/record/3352197. Scripts used for the analysis of genomic data are available at: https://github.com/kumarsaurabh20/Maniola_jurtina_genome_sequencing. Supplemental material available at FigShare: https://doi.org/10.25387/g3.11594187Meadow brown butterflies (Maniola jurtina) on the Isles of Scilly represent an ideal model in which to dissect the links between genotype, phenotype and long-term patterns of selection in the wild - a largely unfulfilled but fundamental aim of modern biology. To meet this aim, a clear description of genotype is required. Here we present the draft genome sequence of M. jurtina to serve as a founding genetic resource for this species. Seven libraries were constructed using pooled DNA from five wild caught spotted females and sequenced using Illumina, PacBio RSII and MinION technology. A novel hybrid assembly approach was employed to generate a final assembly with an N50 of 214 kb (longest scaffold 2.9 Mb). The sequence assembly described here predicts a gene count of 36,294 and includes variants and gene duplicates from five genotypes. Core BUSCO (Benchmarking Universal Single-Copy Orthologs) gene sets of Arthropoda and Insecta recovered 90.5% and 88.7% complete and single-copy genes respectively. Comparisons with 17 other Lepidopteran species placed 86.5% of the assembled genes in orthogroups. Our results provide the first high-quality draft genome and annotation of the butterfly M. jurtina.European Research Council (ERC)Natural Environment Research Council (NERC)Leverhulme TrustRoyal SocietyUniversity of Exete

Migrations and habitat use of the smooth hammerhead shark (Sphyrna zygaena) in the Atlantic Ocean

The smooth hammerhead shark, Sphyrna zygaena, is a cosmopolitan semipelagic shark captured as bycatch in pelagic oceanic fisheries, especially pelagic longlines targeting swordfish and/or tunas. From 2012 to 2016, eight smooth hammerheads were tagged with Pop-up Satellite Archival Tags in the inter-tropical region of the Northeast Atlantic Ocean, with successful transmissions received from seven tags (total of 319 tracking days). Results confirmed the smooth hammerhead is a highly mobile species, as the longest migration ever documented for this species (> 6600 km) was recorded. An absence of a diel vertical movement behavior was noted, with the sharks spending most of their time at surface waters (0-50 m) above 23 degrees C. The operating depth of the pelagic long-line gear was measured with Minilog Temperature and Depth Recorders, and the overlap with the species vertical distribution was calculated. The overlap is taking place mainly during the night and is higher for juveniles (similar to 40% of overlap time). The novel information presented can now be used to contribute to the provision of sustainable management tools and serve as input for Ecological Risk Assessments for smooth hammerheads caught in Atlantic pelagic longline fisheries.Oceanario de Lisboa through Project "SHARK-TAG: Migrations and habitat use of the smooth hammerhead shark in the Atlantic Ocean"; Investigador-FCT from the Portuguese Foundation for Science and Technology (FCT, Fundacao para a Ciencia e Tecnologia) [Ref: IF/00253/2014]; EU European Social Fund; Programa Operacional Potencial Human

Failure to confirm allelic and haplotypic association between markers at the chromosome 6p22.3 dystrobrevin-binding protein 1 (DTNBP1) locus and schizophrenia

Background: Previous linkage and association studies may have implicated the Dystrobrevin-binding protein 1 (DTNBP1) gene locus or a gene in linkage disequilibrium with DTNBP1 on chromosome 6p22.3 in genetic susceptibility to schizophrenia.Methods: We used the case control design to test for of allelic and haplotypic association with schizophrenia in a sample of four hundred and fifty research subjects with schizophrenia and four hundred and fifty ancestrally matched supernormal controls. We genotyped the SNP markers previously found to be significantly associated with schizophrenia in the original study and also other markers found to be positive in subsequent studies.Results: We could find no evidence of allelic, genotypic or haplotypic association with schizophrenia in our UK sample.Conclusion: The results suggest that the DTNBP1 gene contribution to schizophrenia must be rare or absent in our sample. The discrepant allelic association results in previous studies of association between DTNBP1 and schizophrenia could be due population admixture. However, even positive studies of European populations do not show any consistent DTNBP1 alleles or haplotypes associated with schizophrenia. Further research is needed to resolve these issues. The possible confounding of linkage with association in family samples already showing linkage at 6p22.3 might be revealed by testing genes closely linked to DTNBP1 for allelic association and by restricting family based tests of association to only one case per family