BubR1 allelic effects drive phenotypic heterogeneity in mosaic-variegated aneuploidy progeria syndrome

Mosaic-variegated aneuploidy (MVA) syndrome is a rare childhood disorder characterized by biallelic BUBR1, CEP57, or TRIP13 aberrations; increased chromosome missegregation; and a broad spectrum of clinical features, including various cancers, congenital defects, and progeroid pathologies. To investigate the mechanisms underlying this disorder and its phenotypic heterogeneity, we mimicked the BUBR1L1012P mutation in mice (BubR1L1002P) and combined it with 2 other MVA variants, BUBR1X753 and BUBR1H, generating a truncated protein and low amounts of wild-type protein, respectively. Whereas BubR1X753/L1002P and BubR1H/X753 mice died prematurely, BubR1H/L1002P mice were viable and exhibited many MVA features, including cancer predisposition and various progeroid phenotypes, such as short lifespan, dwarfism, lipodystrophy, sarcopenia, and low cardiac stress tolerance. Strikingly, although these mice had a reduction in total BUBR1 and spectrum of MVA phenotypes similar to that of BubR1H/H mice, several progeroid pathologies were attenuated in severity, which in skeletal muscle coincided with reduced senescence-associated secretory phenotype complexity. Additionally, mice carrying monoallelic BubR1 mutations were prone to select MVA-related pathologies later in life, with predisposition to sarcopenia correlating with mTORC1 hyperactivity. Together, these data demonstrate that BUBR1 allelic effects beyond protein level and aneuploidy contribute to disease heterogeneity in both MVA pa...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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You're reading 8 Nootropics to Stimulate Your Brain This Fall, originally posted on Pick the Brain | Motivation and Self Improvement. If you're enjoying this, please visit our site for more inspirational articles. Nootropics is a term coined by Dr. Corneliu E. Giurgea to describe a class of drugs, supplements, and other synthetic and naturally occurring compounds that improve cognitive function in our brains. They’re often called “smart drugs,” as they can help us think faster and more efficiently. Although used by pretty much everyone, these nootropic supplements are especially popular among youn...
Source: PickTheBrain | Motivation and Self Improvement - Category: Consumer Health News Authors: Tags: featured health and fitness self improvement nootropics pickthebrain Source Type: blogs
Hui-Min Liu1,2, Qin Hu3, Qiang Zhang4, Guan-Yue Su5, Hong-Mei Xiao1,2, Bo-Yang Li1,2, Wen-Di Shen1,2, Xiang Qiu1,2, Wan-Qiang Lv1,2 and Hong-Wen Deng1,2,6* 1Center of System Biology and Data Information, School of Basic Medical Science, Central South University, Changsha, China 2Center of Reproductive Health, School of Basic Medical Science, Central South University, Changsha, China 3Kangda College of Nanjing Medical University, Nanjing, China 4College of Public Health, Zhengzhou University, Zhengzhou, China 5Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, ...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
In this study, a link between mitochondrial changes and infant temperament has also been suggested. Maternal psychosocial stress and lifetime trauma have been associated with decreased mitochondrial DNA copy number in the placenta (115, 116).IndividualityChronic stress links changes in the epigenetic landscape with health conditions (117). Different cell types are characterized by distinct patterns of gene expression due to developmental, environmental, physiological, and pathological reasons (117). Epigenetic mechanisms affect gene function in a dynamic way as a result of different environmental exposures during fetal dev...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Conclusion In Table 1, an overview is presented of the complex roles of AAs described in this review regarding the microbiome-gut-immune-brain axis in ASD. Besides behavioral deficits, people with ASD are characterized by systemic inflammation, gastrointestinal immune-related disturbances and changes in the gut microbiota composition. Moreover, differences in levels of specific AAs in various body compartments, including the intestinal tract, blood, urine and brain have been reported in patients with ASD, as well as in rodent models for ASD. This review described that specific AAs can modulate the intestinal epithelial im...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Conclusion Analysis of the pleiotropic effects of IL-33 on multiple immunological cells (macrophages, mastocytes), as well as neurological cells of medulla oblongata, dorsal root ganglion, antigen-induced arthritis system, carrageen, and formalin, shows that this alarmin plays curtail, yet not fully known role in mediating inflammation, especially in chronic inflammatory pulmonary diseases such as asthma, COPD, and OSA. Taken into consideration the engagement in this process, in particular of mastocytes and their secretion of CXCL2, 4, 8, and other cytokines, there is no doubt regarding the etiopathogenic role of IL-33 in...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractThe association between social anxiety disorder (SAD) and attention-deficit/hyperactivity disorder (ADHD) is poorly established. In fact, increasing and converging evidences suggest that there is a close relationship between the two disorders. High comorbidity rate between these two disorders, follow-up studies showing high rates of later development of SAD in ADHD and treatment studies in which ADHD medications have been helpful for both conditions all indicate this relationship. Recently, we have published a hypothesis regarding the development of SAD secondary to ADHD. In this hypothesis, we recognized that pati...
Source: ADHD Attention Deficit and Hyperactivity Disorders - Category: Psychiatry Source Type: research
Much of what we think we know about cannabis may soon change as a result of new research that uncovers some surprising facts. Indeed, the topic, which can be emotionally charged, is the focus of intense scientific study. Is cannabis good for you? Is it addictive? What long-term harms can use cause? The answers to these questions are multi-layered and not always clear-cut, which is why cannabis research continues with even more urgency. FACTS ON CANNABIS ADDICTION AND DEPENDENCE Current estimates are that one in 10 cannabis users will develop cannabis addiction or dependence. The potency of the delta-9-tetrahydrocannabinol ...
Source: Psych Central - Category: Psychiatry Authors: Tags: Addictions Habits Healthy Living Memory and Perception Miscellaneous Drugs Neuroscience Substance Abuse Source Type: news
AbstractThe consequences of atopic dermatitis reach beyond the skin and past childhood. Patients with atopic dermatitis are at risk of developing allergic comorbidities, but less is known about the associations between atopic dermatitis and non-allergic conditions. Understanding these non-allergic comorbidities has the potential to improve patient outcomes and to help mitigate the cost and burdens associated with these conditions. Atopic dermatitis is associated with cutaneous bacterial infections, more severe forms/courses of cutaneous viral infections, and extra-cutaneous infections. Atopic dermatitis is also associated ...
Source: American Journal of Clinical Dermatology - Category: Dermatology Source Type: research
Abstract The 21st century has witnessed the discovery of multiple rare and common gene variants associated with attention deficit hyperactivity disorder (ADHD), and these discoveries have already provided a starting point for the investigation of the biology of the disorder and novel treatments. The purpose of this selective review is to examine genetic findings from the past 5 years and consider their implications for the conceptualization of ADHD and future clinical practice. Recent discoveries reveal the strong genetic overlaps between ADHD and autism spectrum disorder (ASD) as well as intellectual disability. ...
Source: The American Journal of Psychiatry - Category: Psychiatry Authors: Tags: Am J Psychiatry Source Type: research
Semin Hear 2018; 39: 321-333 DOI: 10.1055/s-0038-1666821This perspective explores common pediatric diagnoses that could present with central vestibular pathway dysfunction, leading to delays in motor development and postural control, and gaze instability. Specifically, the following diagnoses are considered: cerebral palsy, myelomeningocele, vestibular migraine, attention-deficit hyperactivity disorder, developmental coordination disorder, concussion, childhood cancer, congenital muscular torticollis, adolescent idiopathic scoliosis, and autism. Suggestions for clinical screening, vestibular function testing, and vestibula...
Source: Seminars in Hearing - Category: Audiology Authors: Tags: Review Article Source Type: research
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