Investigating the role of ASCC1 in the causation of bone fragility

Bi-allelic variants in ASCC1 cause the ultrarare bone fragility disorder “spinal muscular atrophy with congenital bone fractures-2” (SMABF2). However, the mechanism by which ASCC1 dysfunction leads to this musculoskeletal condition and the nature of the associated bone defect are poorly understood. By exome sequencing, we identified a novel homozygous deletion in ASCC1 in a female infant. She was born with severe muscular hypotonia, inability to breathe and swallow, and virtual absence of spontaneous movements; showed progressive brain atrophy, gracile long bones, very slender ribs, and a femur fracture; and died from respiratory failure aged 3 months. A transiliac bone sample taken postmortem revealed a distinct microstructural bone phenotype with low trabecular bone volume, low bone remodeling, disordered collagen organization, and an abnormally high bone marrow adiposity. Proteomics, RNA sequencing, and qPCR in patient-derived skin fibroblasts confirmed that ASCC1 was hardly expressed on protein and RNA levels compared with healthy controls. Furthermore, we demonstrate that mutated ASCC1 is associated with a downregulation of RUNX2, the master regulator of osteoblastogenesis, and SERPINF1, which is involved in osteoblast and adipocyte differentiation. It also exerts an inhibitory effect on TGF-β/SMAD signaling, which is important for bone development. Additionally, knockdown of ASCC1 in human mesenchymal stromal cells (hMSCs) suppressed their differentiation capacity into osteoblasts while increasing their differentiation into adipocytes. This resulted in reduced mineralization and elevated formation of lipid droplets. These findings shed light onto the pathophysiologic mechanisms underlying SMABF2 and assign a new biological role to ASCC1 acting as an important pro-osteoblastogenic and anti-adipogenic regulator.</p

Computer Algorithms To Detect Bloodstream Infections

Automated bloodstream infection surveillance using electronic data is an accurate alternative to surveillance using manually collected data

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Graduate recital in classic guitar

Includes recorded audio recordings in WAV and MP3 formats, 66:32 in length.The selection of works performed in this recital is intended to display a wide variety of musical styles in pieces which are challenging, both technically and interpretively, and are reflective of my personal interests and development as a musician and guitarist during the past two years of graduate study at CSUN. The six pavanes of Spanish vihuelist Luys Milan are from his famous treatise El Maestro (1536). Milan directs that each pavane be repeated, an unspecified number of times, with increasing ornamental variation. (See more in text)..

Excitons in the thallous halides

A thin film fabrication technique resulting in a considerable reduction in strain has been developed and has facilitated the optical and magneto-optical experiments on the Thallous Halides. The strain reduction achieved has revealed optical spectra of exceptional sharpness, Previously undiscovered absorption features have appeared and exciton effects have been established. A variety of experiments were performed to clarify the nature of the structure associated with the first exciton peak. Intrinsic structure and structure due to strain lifted degeneracy has been identified. These experiments also provided criteria for evaluating the films. Analysis of the optical absorption spectra to yield the optical constants was performed and the spectra correlated with the magnetoabsorption results. Both Faraday rotation and direct magneto-absorption experiments were performed. Analysis of the experiments yielded exciton binding energies, effective reduced and carrier masses, effective g values, the energy gaps, peak positions and spin orbit splittings. A phonon sideband to the first exciton peak has been found and its character extensively investigated. The sideband is believed to arise from an exciton-longitudinal optical phonon coupled state.U of I OnlyThesi

The Nutritional Value and Health Benefits of Chickpeas and Hummus

The 2015–2020 Dietary Guidelines for Americans advocate for increasing vegetable intake and replacing energy-dense foods with those that are nutrient-dense. Most Americans do not eat enough vegetables, and particularly legumes, each day, despite their well-established benefits for health. Traditional hummus is a nutrient-dense dip or spread made from cooked, mashed chickpeas, blended with tahini, olive oil, lemon juice, and spices. Consumers of chickpeas and/or hummus have been shown to have higher nutrient intakes of dietary fiber, polyunsaturated fatty acids, vitamin A, vitamin E, vitamin C, folate, magnesium, potassium, and iron as compared to non-consumers. Hummus consumers have also been shown to have higher Healthy Eating Index 2005 (HEI-2005) scores. This may be, in part, due to hummus’ higher Naturally Nutrient Rich (NNR) score as compared to other dips and spreads. Emerging research suggests that chickpeas and hummus may play a beneficial role in weight management and glucose and insulin regulation, as well as have a positive impact on some markers of cardiovascular disease (CVD). Raw or cooked chickpeas and hummus also contain dietary bioactives such as phytic acid, sterols, tannins, carotenoids, and other polyphenols such as isoflavones, whose benefits may extend beyond basic nutrition requirements of humans. With chickpeas as its primary ingredient, hummus—and especially when paired with vegetables and/or whole grains—is a nutritious way for Americans to obtain their recommended servings of legumes. This manuscript reviews the nutritional value and health benefits of chickpeas and hummus and explores how these foods may help improve the nutrient profiles of meals

Excitons in the thallous halides /

Diss. doct. phil. in physic