Elucidating the regulation and function of circRNAs

Circular RNAs (circRNAs) are a newly appreciated class of RNAs that are expressed in a wide range of organisms, tissues, and disease states. The factors regulating circRNA biogenesis are poorly understood. CircRNAs are typically produced from exons of protein-coding genes through a process termed backsplicing. CircRNAs are enriched in the brain compared to other tissues in humans, and increase globally in expression during neuronal differentiation. In Chapter 2, we discovered that the neural-enriched splicing factor NOVA2 positively regulates hundreds of circRNAs in the developing mouse brain. We found that this regulation occurs through NOVA2 binding within introns flanking circRNA loci. This work identified the first RNA binding protein that facilitates circRNA enrichment in the mammalian brain.CircRNAs accumulate during aging across various organisms, especially in the brain. What functions, if any, do these age-related circRNAs have? A considerable roadblock to studying circRNA function has been the difficulty to establish circRNA-specific mutants. In Chapter 3 we identified sequences in introns that were important for circularization of two age-regulated circRNAs expressed from the crh-1 gene in the nematode C. elegans. Using CRISPRCas9, we generated intronic deletions that completely abolished crh-1 circRNAs without interrupting linear crh-1 mRNA expression. Remarkably, we found thatelimination of these circRNAs increased mean lifespan in C. elegans, suggesting that they contribute to age-related decline

ASSESSMENT OF A LINE TRANSECT FIELD METHOD TO DETERMINE WINTER TICK ABUNDANCE ON MOOSE

High infestations of winter ticks (Dermacentor albipictus) can exact high physiological costs on moose and are associated with high rates of juvenile mortality. Quantifying tick abundance on moose may help managers calculate overall mortality rates for moose and make harvest recommendations. We compared winter tick counts along hair transects on samples of moose hides to tick counts obtained from chemical digestion of those same samples. Winter tick counts from the two methods were strongly correlated (P <0.001, r2 = 0.88, n = 31). We field-tested the hair transect count method to determine its practicality at moose check stations. Tick counts on 4 body areas per moose (n = 60) generally took ≤10 minutes and were rapid, non-destructive, inexpensive, and easily employed. This method has potential to serve as an effective method to index winter tick loads on moose

The 2015 Plains Elevated Convection at Night Field Project

The central Great Plains region in North America has a nocturnal maximum in warm-season precipitation. Much of this precipitation comes from organized mesoscale convective systems (MCSs). This nocturnal maximum is counterintuitive in the sense that convective activity over the Great Plains is out of phase with the local generation of CAPE by solar heating of the surface. The lower troposphere in this nocturnal environment is typically characterized by a low-level jet (LLJ) just above a stable boundary layer (SBL), and convective available potential energy (CAPE) values that peak above the SBL, resulting in convection that may be elevated, with source air decoupled from the surface. Nocturnal MCS-induced cold pools often trigger undular bores and solitary waves within the SBL. A full understanding of the nocturnal precipitation maximum remains elusive, although it appears that bore-induced lifting and the LLJ may be instrumental to convection initiation and the maintenance of MCSs at night. To gain insight into nocturnal MCSs, their essential ingredients, and paths toward improving the relatively poor predictive skill of nocturnal convection in weather and climate models, a large, multiagency field campaign called Plains Elevated Convection At Night (PECAN) was conducted in 2015. PECAN employed three research aircraft, an unprecedented coordinated array of nine mobile scanning radars, a fixed S-band radar, a unique mesoscale network of lower-tropospheric profiling systems called the PECAN Integrated Sounding Array (PISA), and numerous mobile-mesonet surface weather stations. The rich PECAN dataset is expected to improve our understanding and prediction of continental nocturnal warm-season precipitation. This article provides a summary of the PECAN field experiment and preliminary findings

The verdict geometric quality library.

Verdict is a collection of subroutines for evaluating the geometric qualities of triangles, quadrilaterals, tetrahedra, and hexahedra using a variety of metrics. A metric is a real number assigned to one of these shapes depending on its particular vertex coordinates. These metrics are used to evaluate the input to finite element, finite volume, boundary element, and other types of solvers that approximate the solution to partial differential equations defined over regions of space. The geometric qualities of these regions is usually strongly tied to the accuracy these solvers are able to obtain in their approximations. The subroutines are written in C++ and have a simple C interface. Each metric may be evaluated individually or in combination. When multiple metrics are evaluated at once, they share common calculations to lower the cost of the evaluation

Large Proteoglycan Complexes and Disturbed Collagen Architecture in the Corneal Extracellular Matrix of Mucopolysaccharidosis Type VII (Sly Syndrome)

Purpose. Deficiencies in enzymes involved in proteoglycan (PG) turnover underlie a number of rare mucopolysaccharidoses (MPS), investigations of which can considerably aid understanding of the roles of PGs in corneal matrix biology. Here, the authors analyze novel pathologic changes in MPS VII (Sly syndrome) to determine the nature of PG-collagen associations in stromal ultrastructure. Methods. Transmission electron microscopy and electron tomography were used to investigate PG-collagen architectures and interactions in a cornea obtained at keratoplasty from a 22-year-old man with MPS VII, which was caused by a compound heterozygous mutation in the GUSB gene. Results. Transmission electron microscopy showed atypical morphology of the epithelial basement membrane and Bowman's layer in MPS VII. Keratocytes were packed with cytoplasmic vacuoles containing abnormal glycosaminoglycan (GAG) material, and collagen fibrils were thinner than in normal cornea and varied considerably throughout anterior (14–32 nm), mid (13–42 nm), and posterior (17–39 nm) regions of the MPS VII stroma. PGs viewed in three dimensions were striking in appearance in that they were significantly larger than PGs in normal cornea and formed highly extended linkages with multiple collagen fibrils. Conclusions. Cellular changes in the MPS VII cornea resemble those in other MPS. However, the wide range of collagen fibril diameters throughout the stroma and the extensive matrix presence of supranormal-sized PG structures appear to be unique features of this disorder. The findings suggest that the accumulation of stromal chondroitin-, dermatan-, and heparan-sulfate glycosaminoglycans in the absence of β-glucuronidase-mediated degradation can modulate collagen fibrillogenesis

Highlights From the Annual Meeting of the American Epilepsy Society 2022

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia

American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus

10.1002/acr.23834ARTHRITIS CARE & RESEARCH715579-59