Orange Arts and Economic Development: Identifying Non-Traditional Innovative Educational Opportunities for Economic Development in the Town of Orange, Massachusetts

The purpose of this collaboration is to develop creative, ‘out of the box’ solutions for a wide range of economic development issues in Franklin County, Massachusetts. One area of focus is in identifying innovative and educational opportunities that promote economic development strategies for the town of Orange, Massachusetts

Downtown Athol: A Revitalization Plan (Athol, MA)

The goal of the Master of Regional Planning Studio is to develop a student’s techniques for collecting, analyzing, and synthesizing spatial and non-spatial data and then presenting that collective data in a manner (i.e., report, video, presentation, and charettes) that is understandable to academics, professionals, and the public. Planning Studio allows students to integrate knowledge from coursework and research, and apply such knowledge to resolving representative planning problems. At UMASS Amherst, these problems are found in neighborhood, rural, urban, and/or regional settings. In the fall of 2014, three local governments contracted with the MRP Studio to create separate vision plans that focused on key aspects of community revitalization. Like other New England mill towns, the Town of Athol has been subject to the economic shocks of the last half century, which has seen major industries relocate out of state or off-shore. The consequences of the loss of major industry can be seen boarded up factory buildings and a Main Street struggling to maintain its identity. Athol tasked the graduate student team (Millers River Consulting) with delivering creative, out-of-the-box suggestions to help revitalize its downtown

European communication networks in the Early Modern Age

Recent contributions to knowledge about early journalism developed in different parts of Europe*Italy, France, England, Germany, the Netherlands, Portugal, Spain . . . *have made it possible to trace a fairly precise map for the historical origin of this phenomenon. However, the scope of work carried out with a view to developing frameworks of interpretation to explain the reasons for this appearance is not as far-reaching. This paper reviews the recurring theoretical models found to date in the specific bibliography and proposes a new framework of interpretation, capable of encompassing the complexity and pan-European nature of early journalism in history

The prevalence of diseases caused by lysosome-related genes in a cohort of undiagnosed patients

Lysosomal diseases (LD) comprise a group of approximately 60 hereditary conditions caused by progressive accumulation of metabolites due to defects in lysosomal enzymes and degradation pathways, which lead to a wide range of clinical manifestations. The estimated combined incidence of LD is between 1 in 4000 to 1 in 13,000 live births, with recent data from pilot newborn screening studies showing even higher incidence. We aimed to determine the prevalence of the classical LD and other diseases caused by lysosome-related genes in our cohort of diagnostic odyssey patients. The Individualized Medicine Clinic at Mayo Clinic is increasingly utilizing whole exome sequencing (WES) to determine the genetic etiology of undiagnosed Mendelian disease. From September 2012 to April 2017, WES results from 350 patients with unexplained symptoms were reviewed. Disease-causing variants were identified in MYO6, CLN6, LRBA, KCTD7, and ARSB revealing a genetic diagnosis of a LD in 8 individuals from 5 families. Based on our findings, lysosome-related disorders may be collectively common, reaching up to 1.5% prevalence in a cohort of patients with undiagnosed diseases presenting to a genetics clinic

RINT1 Bi-allelic variations cause infantile-onset recurrent acute liver failure and skeletal abnormalities

Pediatric acute liver failure (ALF) is life threatening with genetic, immunologic, and environmental etiologies. Approximately half of all cases remain unexplained. Recurrent ALF (RALF) in infants describes repeated episodes of severe liver injury with recovery of hepatic function between crises. We describe bi-allelic RINT1 alterations as the cause of a multisystem disorder including RALF and skeletal abnormalities. Three unrelated individuals with RALF onset ≤3 years of age have splice alterations at the same position (c.1333+1G>A or G>T) in trans with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del) in RINT1. ALF episodes are concomitant with fever/infection and not all individuals have complete normalization of liver function testing between episodes. Liver biopsies revealed nonspecific liver damage including fibrosis, steatosis, or mild increases in Kupffer cells. Skeletal imaging revealed abnormalities affecting the vertebrae and pelvis. Dermal fibroblasts showed splice-variant mediated skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay. Fibroblasts also revealed decreased RINT1 protein, abnormal Golgi morphology, and impaired autophagic flux compared to control. RINT1 interacts with NBAS, recently implicated in RALF, and UVRAG, to facilitate Golgi-to-ER retrograde vesicle transport. During nutrient depletion or infection, Golgi-to-ER transport is suppressed and autophagy is promoted through UVRAG regulation by mTOR. Aberrant autophagy has been associated with the development of similar skeletal abnormalities and also with liver disease, suggesting that disruption of these RINT1 functions may explain the liver and skeletal findings. Clarifying the pathomechanism underlying this gene-disease relationship may inform therapeutic opportunities