Region-Specific Microstructure in the Neonatal Ventricles of a Porcine Model

© 2018, Biomedical Engineering Society. The neonate transitions from placenta-derived oxygen, to supply from the pulmonary system, moments after birth. This requires a series of structural developments to divert more blood through the right heart and onto the lungs, with the tissue quickly remodelling to the changing ventricular workload. In some cases, however, the heart structure does not fully develop causing poor circulation and inefficient oxygenation, which is associated with an increase in mortality and morbidity. This study focuses on developing an enhanced knowledge of the 1-day old heart, quantifying the region-specific microstructural parameters of the tissue. This will enable more accurate mathematical and computational simulations of the young heart. Hearts were dissected from 12, 1-day-old deceased Yorkshire piglets (mass: 2.1–2.4kg, length: 0.38–0.51m), acquired from a breeding farm. Evans blue dye was used to label the heart equator and to demarcate the left and right ventricle free walls. Two hearts were used for three-dimensional diffusion-tensor magnetic resonance imaging, to quantify the fractional anisotropy (FA). The remaining hearts were used for two-photon excited fluorescence and second-harmonic generation microscopy, to quantify the cardiomyocyte and collagen fibril structures within the anterior and posterior aspects of the right and left ventricles. FA varied significantly across both ventricles, with the greatest in the equatorial region, followed by the base and apex. The FA in each right ventricular region was statistically greater than that in the left. Cardiomyocyte and collagen fibre rotation was greatest in the anterior wall of both ventricles, with less dispersion when compared to the posterior walls. In defining these key parameters, this study provides a valuable insight into the 1-day-old heart that will provide a valuable platform for further investigation the normal and abnormal heart using mathematical and computational models

Editor's Choice – European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on Radiation Safety

info:eu-repo/semantics/publishedVersio

Editor's Choice – European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on the Management of Atherosclerotic Carotid and Vertebral Artery Disease

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Gene expression analyses in breast cancer epidemiology: the Norwegian Women and Cancer postgenome cohort study

Introduction The introduction of high-throughput technologies, also called -omics technologies, into epidemiology has raised the need for high-quality observational studies to reduce several sources of error and bias. Methods The Norwegian Women and Cancer (NOWAC) postgenome cohort study consists of approximately 50,000 women born between 1943 and 1957 who gave blood samples between 2003 and 2006 and filled out a two-page questionnaire. Blood was collected in such a way that RNA is preserved and can be used for gene expression analyses. The women are part of the NOWAC study consisting of 172,471 women 30 to 70 years of age at recruitment from 1991 to 2006 who answered one to three questionnaires on diet, medication use, and lifestyle. In collaboration with the Norwegian Breast Cancer Group, every NOWAC participant born between 1943 and 1957 who is admitted to a collaborating hospital for a diagnostic biopsy or for surgery of breast cancer will be asked to donate a tumor biopsy and two blood samples. In parallel, at least three controls are approached for each breast cancer case in order to obtain blood samples from at least two controls per case. The controls are drawn at random from NOWAC matched by time of follow-up and age. In addition, 400 normal breast tissues as well as blood samples will be collected among healthy women participating at the Norwegian Mammography Screening program at the Breast Imaging Center at the University Hospital of North-Norway, Tromsø. Results The NOWAC postgenome cohort offers a unique opportunity (a) to study blood-derived gene expression profiles as a diagnostic test for breast cancer in a nested case-control design with adjustment for confounding factors related to different exposures, (b) to improve the reliability and accuracy of this approach by adjusting for an individual's genotype (for example, variants in genes coding for hormone and drug-metabolizing and detoxifying enzymes), (c) to study gene expression profiles from peripheral blood as surrogate tissue to biomonitor defined exposure (for example, hormone) and its association with disease risk (that is, breast cancer), and (d) to study gene variants (single nucleotide polymorphisms and copy number variations) and environmental exposure (endogenous and exogenous hormones) and their influence on the incidence of different molecular subtypes of breast cancer. Conclusion The NOWAC postgenome cohort combining a valid epidemiological approach with richness of biological samples should make an important contribution to the study of the etiology and system biology of breast cancer

Deciphering Normal Blood Gene Expression Variation—The NOWAC Postgenome Study

There is growing evidence that gene expression profiling of peripheral blood cells is a valuable tool for assessing gene signatures related to exposure, drug-response, or disease. However, the true promise of this approach can not be estimated until the scientific community has robust baseline data describing variation in gene expression patterns in normal individuals. Using a large representative sample set of postmenopausal women (N = 286) in the Norwegian Women and Cancer (NOWAC) postgenome study, we investigated variability of whole blood gene expression in the general population. In particular, we examined changes in blood gene expression caused by technical variability, normal inter-individual differences, and exposure variables at proportions and levels relevant to real-life situations. We observe that the overall changes in gene expression are subtle, implying the need for careful analytic approaches of the data. In particular, technical variability may not be ignored and subsequent adjustments must be considered in any analysis. Many new candidate genes were identified that are differentially expressed according to inter-individual (i.e. fasting, BMI) and exposure (i.e. smoking) factors, thus establishing that these effects are mirrored in blood. By focusing on the biological implications instead of directly comparing gene lists from several related studies in the literature, our analytic approach was able to identify significant similarities and effects consistent across these reports. This establishes the feasibility of blood gene expression profiling, if they are predicated upon careful experimental design and analysis in order to minimize confounding signals, artifacts of sample preparation and processing, and inter-individual differences

Physiological Stress and Refuge Behavior by African Elephants

Physiological stress responses allow individuals to adapt to changes in their status or surroundings, but chronic exposure to stressors could have detrimental effects. Increased stress hormone secretion leads to short-term escape behavior; however, no studies have assessed the potential of longer-term escape behavior, when individuals are in a chronic physiological state. Such refuge behavior is likely to take two forms, where an individual or population restricts its space use patterns spatially (spatial refuge hypothesis), or alters its use of space temporally (temporal refuge hypothesis). We tested the spatial and temporal refuge hypotheses by comparing space use patterns among three African elephant populations maintaining different fecal glucocorticoid metabolite (FGM) concentrations. In support of the spatial refuge hypothesis, the elephant population that maintained elevated FGM concentrations (iSimangaliso) used 20% less of its reserve than did an elephant population with lower FGM concentrations (Pilanesberg) in a reserve of similar size, and 43% less than elephants in the smaller Phinda reserve. We found mixed support for the temporal refuge hypothesis; home range sizes in the iSimangaliso population did not differ by day compared to nighttime, but elephants used areas within their home ranges differently between day and night. Elephants in all three reserves generally selected forest and woodland habitats over grasslands, but elephants in iSimangaliso selected exotic forest plantations over native habitat types. Our findings suggest that chronic stress is associated with restricted space use and altered habitat preferences that resemble a facultative refuge behavioral response. Elephants can maintain elevated FGM levels for ≥6 years following translocation, during which they exhibit refuge behavior that is likely a result of human disturbance and habitat conditions. Wildlife managers planning to translocate animals, or to initiate other management activities that could result in chronic stress responses, should consider the potential for, and consequences of, refuge behavior

Sequence comparison of prefrontal cortical brain transcriptome from a tame and an aggressive silver fox (Vulpes vulpes)

<p>Abstract</p> <p>Background</p> <p>Two strains of the silver fox (<it>Vulpes vulpes</it>), with markedly different behavioral phenotypes, have been developed by long-term selection for behavior. Foxes from the tame strain exhibit friendly behavior towards humans, paralleling the sociability of canine puppies, whereas foxes from the aggressive strain are defensive and exhibit aggression to humans. To understand the genetic differences underlying these behavioral phenotypes fox-specific genomic resources are needed.</p> <p>Results</p> <p>cDNA from mRNA from pre-frontal cortex of a tame and an aggressive fox was sequenced using the Roche 454 FLX Titanium platform (> 2.5 million reads & 0.9 Gbase of tame fox sequence; >3.3 million reads & 1.2 Gbase of aggressive fox sequence). Over 80% of the fox reads were assembled into contigs. Mapping fox reads against the fox transcriptome assembly and the dog genome identified over 30,000 high confidence fox-specific SNPs. Fox transcripts for approximately 14,000 genes were identified using SwissProt and the dog RefSeq databases. An at least 2-fold expression difference between the two samples (p < 0.05) was observed for 335 genes, fewer than 3% of the total number of genes identified in the fox transcriptome.</p> <p>Conclusions</p> <p>Transcriptome sequencing significantly expanded genomic resources available for the fox, a species without a sequenced genome. In a very cost efficient manner this yielded a large number of fox-specific SNP markers for genetic studies and provided significant insights into the gene expression profile of the fox pre-frontal cortex; expression differences between the two fox samples; and a catalogue of potentially important gene-specific sequence variants. This result demonstrates the utility of this approach for developing genomic resources in species with limited genomic information.</p

Massive-Scale RNA-Seq Analysis of Non Ribosomal Transcriptome in Human Trisomy 21

Hybridization- and tag-based technologies have been successfully used in Down syndrome to identify genes involved in various aspects of the pathogenesis. However, these technologies suffer from several limits and drawbacks and, to date, information about rare, even though relevant, RNA species such as long and small non-coding RNAs, is completely missing. Indeed, none of published works has still described the whole transcriptional landscape of Down syndrome. Although the recent advances in high-throughput RNA sequencing have revealed the complexity of transcriptomes, most of them rely on polyA enrichment protocols, able to detect only a small fraction of total RNA content. On the opposite end, massive-scale RNA sequencing on rRNA-depleted samples allows the survey of the complete set of coding and non-coding RNA species, now emerging as novel contributors to pathogenic mechanisms. Hence, in this work we analysed for the first time the complete transcriptome of human trisomic endothelial progenitor cells to an unprecedented level of resolution and sensitivity by RNA-sequencing. Our analysis allowed us to detect differential expression of even low expressed genes crucial for the pathogenesis, to disclose novel regions of active transcription outside yet annotated loci, and to investigate a plethora of non-polyadenilated long as well as short non coding RNAs. Novel splice isoforms for a large subset of crucial genes, and novel extended untranslated regions for known genes—possibly novel miRNA targets or regulatory sites for gene transcription—were also identified in this study. Coupling the rRNA depletion of samples, followed by high-throughput RNA-sequencing, to the easy availability of these cells renders this approach very feasible for transcriptome studies, offering the possibility of investigating in-depth blood-related pathological features of Down syndrome, as well as other genetic disorders