Avian Cardiovascular Disease Characteristics, Causes and Genomics

Cardiovascular disease is common in avian species and increasing commercial economic losses and demand for healthcare in the household/smallholding veterinary sector has resulted in increased research into these disorders. This in turn has highlighted the importance of breeding, genetic testing and possibilities for future prognostic and diagnostic testing. Research into avian cardiovascular genetics has rapidly accelerated. Previously much work was undertaken in mammals with information extrapolated and transferred to birds. Birds have also been used to model cardiovascular disease and therefore knowledge has become enriched due to this endeavour. Increasingly, the avian genome is being analysed in its own right. This work is assisted by the growing number of avian genomes being published. In 2015, Nature published news on the ‘Bird 10K’ project, which aims to sequence 10,500 extant bird species. By 2018, the Avian Genomes Consortium had published the sequences of 45 species/34 orders. This review investigates a range of avian cardiovascular disorders in order to highlight their pathologies, epidemiology and genetics in addition to avian models of heart disease. With the availability of more reference genomes, increases in the number and magnitude of avian studies and more advanced technologies, the genetics behind avian cardiovascular disorders is being unravelled

Development of High-speed Optical Coherence Tomography for Time-lapse Non-destructive Characterization of Samples

Optical coherence tomography (OCT) is an established optical imaging modality which can obtain label-free, non-destructive 3D images of samples with micron-scale resolution and millimeter penetration. OCT has been widely adopted for biomedical researches

Characterisation of Longitudinal Brain Morphology, Neurometabolism and Prenatal to Neonatal Brain Growth in Patients with Congenital Heart Disease

Congenital heart disease (CHD) affect 8 in 1000 newborns (Liu et al. 2019). The consequences of CHD vary greatly, depending on the specific type of CHD. While advancements in surgical techniques and patient care have led to a high survival rate for severe types of CHD, patients are still at risk of impaired neurodevelopment (ND). Early ND impairment can manifest in various domains, including motor, cognitive or language development (Latal 2016). As a result, one area of CHD research is dedicated to studying the brain development of these patients. This thesis focuses on the longitudinal description of brain development during the late fetal and neonatal period. First, we explored whether deformation-based morphometry (DBM) could be a suitable tool to study CHD patients from fetal to neonatal time period by applying this method to a healthy control cohort. Next, we analysed longitudinally collected data from two studies, primarily focusing on quantifying brain development and searching for associations with ND outcomes in CHD patients. In the first study we explored how DBM could be applied to fetal and neonatal MRI data to observe asymmetry changes during this period. By using DBM, we were able to reveal temporal changes of asymmetry patterns. However, the results may greatly depend on the various combinations of analysis tools and their parameters used. In the second study, where we compared brain development in CHD patients to healthy controls, we therefore relied on volume and surface measurements to quantify growth. Here, we could show that the total brain volume growth trajectory for CHD patients was reduced compared to healthy controls. Finally, we investigated neurometabolite ratios in CHD patients and their association to ND outcome. While we found that a specific neurometabolite ratio (NAA/Cho; N-acetylaspartate to choline-containing compounds) was reduced in the CHD cohort compared to healthy controls, we could not find any association with ND outcome measured at one year of age. In conclusion, the work presented in this thesis uses various methods to study brain development in a longitudinal manner. The findings provide further evidence that brain 4 development in CHD patients is altered while its association with ND outcome requires further investigation

The Interplay of Biomechanics, Tissue Polarity and Collective Migration as it Contributes to Early Heart Organogenesis

In early heart development, bilateral fields of heart progenitor cells (HPCs) undergo a large-scale movement from the anterior lateral plate mesoderm to merge on the ventral midline, undergoing a mesenchymal-to-epithelial transition (MET) halfway through this process. While the heart is the first functioning organs in the developing embryo, a comprehensive model for early heart development that integrates both physical mechanisms and molecular signaling pathways remains elusive. Here, we utilize Xenopus embryos to investigate the role of mechanical cues in driving MET in HPCs and show how dysregulation of these cues can cause congenital heart defects (CHDs). Small molecule inhibitor treatments targeting actomyosin contractility reveal a temporally specific requirement of bulk tissue compliance to regulate heart development and MET. Through tracking of tissue level deformations in the heart forming region (HFR) as well as movement trajectories and traction generation of individual HPCs, we find the onset of MET correlates with a peak in mechanical stress within the HFR and changes in HPC migratory behaviors. Targeting mutant constructs to modulate contractility and compliance in the underlying endoderm, we find MET in HPCs can be accelerated in response to microenvironmental stiffening and can be inhibited by softening. To test whether MET in HPCs is responsive to purely physical mechanical cues, we mimicked a high stress state by injecting an inert oil droplet to generate high strain in the HFR, demonstrating that exogenously applied stress is sufficient to drive MET. MET-induced defects in anatomy result in defined functional lesions in the larval heart and furthermore, when we recreate a clinically-relevant CHD phenotype through overexpression of a Noonan Syndrome-associated mutant protein, we find it leads to abnormal MET in HPCs due to a decoupling of force transmission and mechanosensory pathways. From this integrated analysis of HPC polarity and mechanics, we propose that normal heart development requires HPCs to undergo a critical behavioral and phenotypic transition on their way to the ventral midline and that this transition is driven in response to the changing mechanical properties of their endoderm substrate. We conclude that the etiology underlying many CHDs may involve errors in mechanical signaling and MET

Optical Diagnostics in Human Diseases

Optical technologies provide unique opportunities for the diagnosis of various pathological disorders. The range of biophotonics applications in clinical practice is considerably wide given that the optical properties of biological tissues are subject to significant changes during disease progression. Due to the small size of studied objects (from μm to mm) and despite some minimum restrictions (low-intensity light is used), these technologies have great diagnostic potential both as an additional tool and in cases of separate use, for example, to assess conditions affecting microcirculatory bed and tissue viability. This Special Issue presents topical articles by researchers engaged in the development of new methods and devices for optical non-invasive diagnostics in various fields of medicine. Several studies in this Special Issue demonstrate new information relevant to surgical procedures, especially in oncology and gynecology. Two articles are dedicated to the topical problem of breast cancer early detection, including during surgery. One of the articles is devoted to urology, namely to the problem of chronic or recurrent episodic urethral pain. Several works describe the studies in otolaryngology and dentistry. One of the studies is devoted to diagnosing liver diseases. A number of articles contribute to the studying of the alterations caused by diabetes mellitus and cardiovascular diseases. The results of all the presented articles reflect novel innovative research and emerging ideas in optical non-invasive diagnostics aimed at their wider translation into clinical practice

Life Sciences Program Tasks and Bibliography for FY 1997

This document includes information on all peer reviewed projects funded by the Office of Life and Microgravity Sciences and Applications, Life Sciences Division during fiscal year 1997. This document will be published annually and made available to scientists in the space life sciences field both as a hard copy and as an interactive internet web page

Embryonic Stem Cells

Embryonic stem cells are one of the key building blocks of the emerging multidisciplinary field of regenerative medicine, and discoveries and new technology related to embryonic stem cells are being made at an ever increasing rate. This book provides a snapshot of some of the research occurring across a wide range of areas related to embryonic stem cells, including new methods, tools and technologies; new understandings about the molecular biology and pluripotency of these cells; as well as new uses for and sources of embryonic stem cells. The book will serve as a valuable resource for engineers, scientists, and clinicians as well as students in a wide range of disciplines

Cell Biology of Galectins

Galectins are a family of soluble beta-galactoside-binding proteins with diverse glycan-dependent and glycan-independent functions outside and inside the cell. There are sixteen recognized mammalian galectin genes, and their expression profiles are very different between cell types, tissues, and species. This Special Issue covers recent progress in the field of the cell biology of galectins, relevant concepts of galectin regulatory mechanisms, and biomedical aspects of these unique multifunctional proteins