The Deerfield Street Initiative (Greenfield, 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. For the fall 2018 Planning Studio, the Town of Greenfieldtasked the Masters of Regional Planning Studio to prepare a vision plan that focuses on improving Greenfield’sRoute 5 Southern/Deerfield Street Corridor. Greenfield’s Deerfield Street neighborhood serves as the southern gateway to the Downtown. This area has been in transition for several years as the City has invested in housing and infrastructure along this stretch. The key projects have been upgrade of sidewalks, creation of a small riverside park, renovation of distressed housing. Recently, the neighborhood has seen investment in new housing. The Arbors (constructed in 2007) is an upscale assisted housing residence thatalso has low-income housing units. The Green River Commons (2018) consists of eight newhigh performance (energy) modest-sized condominiums with units as fourlow-income housing. In addition, there are several multifamily homes have been or are scheduledfor rehabilitation under the City\u27s Housing Rehab Program

Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy

Autophagy, the process by which proteins and organelles are sequestered in double-membrane structures called autophagosomes and delivered to lysosomes for degradation, is critical in diseases such as cancer and neurodegeneration1,2. Much of our understanding of this process has emerged from analysis of bulk cytoplasmic autophagy, but our understanding of how specific cargo including organelles, proteins, or intracellular pathogens are targeted for selective autophagy is limited3. We employed quantitative proteomics to identify a cohort of novel and known autophagosome-enriched proteins, including cargo receptors. Like known cargo receptors, NCOA4 was highly enriched in autophagosomes, and associated with ATG8 proteins that recruit cargo-receptor complexes into autophagosomes. Unbiased identification of NCOA4-associated proteins revealed ferritin heavy and light chains, components of an iron-filled cage structure that protects cells from reactive iron species4 but is degraded via autophagy to release iron5,6 through an unknown mechanism. We found that delivery of ferritin to lysosomes required NCOA4, and an inability of NCOA4-deficient cells to degrade ferritin leads to decreased bioavailable intracellular iron. This work identifies NCOA4 as a selective cargo receptor for autophagic turnover of ferritin (ferritinophagy) critical for iron homeostasis and provides a resource for further dissection of autophagosomal cargo-receptor connectivity

Similar response rates and survival with PARP inhibitors for patients with solid tumors harboring somatic versus Germline BRCA mutations: a Meta-analysis and systematic review

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background PARP inhibitors (PARPi) have recently been approved for various malignancies based on the results of several clinical trials. However, these trials have mostly recruited patients with germline BRCA mutations, and it is unclear whether PARPi have similar efficacy in patients with somatic BRCA mutations. Our study aimed to determine the efficacy of PARPi in patients with somatic BRCA mutations. Methods We performed a meta-analysis comparing overall response rate to PARPi in patients harboring somatic versus germline BRCA mutations. We looked at studies including somatic and germline mutations in BRCA patients that received PARPi. Results After screening and removing duplicates, 18 studies met our criteria for including both somatic and germline BRCA mutations. Only 8 studies reported response rates for both somatic and germline BRCA mutations. In those studies, 24 out of 43 patients with somatic BRCA mutations (55.8%), and 69 out of 157 (43.9%) patients with germline BRCA patients had a response to therapy to PARPi. This difference was not statistically significant (p = 0.399). In all five studies that reported progression-free survival, there was no obvious difference in outcomes between somatic versus germline BRCA patients, however a precise statistical analysis could not be performed. Conclusion Our meta-analysis and systematic review of the literature indicates similar response rates of PARPi therapy in patients with somatic and germline BRCA mutations. Investigation of use of PARPi therapy in a broader patient population, and the inclusion of somatic BRCA mutations in further clinical trials is paramount in improving therapeutic options for our patients

Molecular definitions of autophagy and related processes.

Over the past two decades, the molecular machinery that underlies autophagic responses has been characterized with ever increasing precision in multiple model organisms. Moreover, it has become clear that autophagy and autophagy-related processes have profound implications for human pathophysiology. However, considerable confusion persists about the use of appropriate terms to indicate specific types of autophagy and some components of the autophagy machinery, which may have detrimental effects on the expansion of the field. Driven by the overt recognition of such a potential obstacle, a panel of leading experts in the field attempts here to define several autophagy-related terms based on specific biochemical features. The ultimate objective of this collaborative exchange is to formulate recommendations that facilitate the dissemination of knowledge within and outside the field of autophagy research

Early versus late endoscopic treatment of pancreatic necrotic collections: A Systematic review and meta-analysis

Background and aims Recently studies have compared early (4 weeks) endoscopic treatment of pancreatic necrotic collections (PNC) and have reported favorable results for early treatment. In this meta-analysis, we compared the efficacy and safety of early vs. late endoscopic treatment of PNC. Methods We reviewed several databases from inception to September 30, 2021 to identify studies that compared early with late endoscopic treatment of PNC. Our outcomes of interest were adverse events, resolution of PNC, performance of direct endoscopic necrosectomy, need for further interventions and mean number of endoscopic necrosectomy sessions. We calculated pooled risk ratios (RR) with 95% confidence intervals (CI) for categorical variables and mean differences (MD) with 95% CI for continuous variables. Data were analyzed by random effect model. Heterogeneity was assessed by I2 statistic. Results We included 4 studies with 427 patients. We found no significant difference in rates of adverse events, RR (95% CI) 1.70 (0.56, 5.20), resolution of necrotic or fluid collections, RR (95% CI) 0.89 (0.71, 1.11), need for further interventions, RR (95% CI) 1.47 (0.70, 3.08), direct necrosectomy, RR (95% CI) 1.39 (0.22, 8.80), mortality, RR (95% CI) 2.37 (0.26, 21.72) and mean number of endoscopic necrosectomy sessions, MD (95% CI) 1.58 (-0.20, 3.36) between groups. Conclusions Early endoscopic treatment of PNC can be considered for indications such as infected necrosis or sterile necrosis with symptoms or complications, however, future large multicenter studies are required to further evaluate its safety

Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis

NCOA4 is a selective cargo receptor for the autophagic turnover of ferritin, a process critical for regulation of intracellular iron bioavailability. However, how ferritinophagy flux is controlled and the roles of NCOA4 in iron-dependent processes are poorly understood. Through analysis of the NCOA4-FTH1 interaction, we demonstrate that direct association via a key surface arginine in FTH1 and a C-terminal element in NCOA4 is required for delivery of ferritin to the lysosome via autophagosomes. Moreover, NCOA4 abundance is under dual control via autophagy and the ubiquitin proteasome system. Ubiquitin-dependent NCOA4 turnover is promoted by excess iron and involves an iron-dependent interaction between NCOA4 and the HERC2 ubiquitin ligase. In zebrafish and cultured cells, NCOA4 plays an essential role in erythroid differentiation. This work reveals the molecular nature of the NCOA4-ferritin complex and explains how intracellular iron levels modulate NCOA4-mediated ferritinophagy in cells and in an iron-dependent physiological setting. DOI: http://dx.doi.org/10.7554/eLife.10308.00

Assessing dementia in people with learning disabilities : the relationship between two screening measures.

As life expectancy increases for people with learning disabilities, the impact of dementia on people with learning disabilities and their families, carers and services is becoming more apparent. Psychological services for learning disabilities are receiving an increasing number of referrals requesting dementia assessment. Health and social care services are adapting to the diverse needs of an ageing population with learning disabilities. This article describes a study investigating the relationship between two assessments for dementia in people with learning disabilities. Carers of people with learning disabilities over the age of 50 (or 40 if the individual had Down syndrome) completed the Dementia Questionnaire for Mentally Retarded People and the Adaptive Behaviour Scale–Residential and Community. Overall, the two questionnaire measures showed significant relationships. However, results suggested that both assessments have clinical value in informing individual needs and aiding diagnosis. Implications for both clinical and social care services are discussed