Donnelly College

La storia della Seconda guerra mondiale in Italia è profondamente segnata dalla complessità della geografia e della cronologia. Bombardamenti, governo alleato, occupazione tedesca, repubblica di Salò, fasi ed eventi dividono il territorio nazionale provocando esperienze e memorie specifiche a volte dissonanti rispetto al discorso pubblico.Il saggio si propone di analizzare il quadro complessivo di un contesto estremamente articolato, privilegiando un approccio di storia sociale che dia voce alle storie dei soggetti nei diversi momenti e nei diversi territori e faccia emergere le contraddizioni e le ambiguità che hanno contrassegnato le vicende delle comunità come delle vite individuali. Una particolare attenzione viene posta sul tema della memoria e del suo processo di costruzione: memorie pubbliche e memorie private, ricordo e rimozione. Viene approfondito il tema del trauma e vengono affrontate insieme le interpretazioni storiografiche che hanno accompagnato negli anni il dibattito pubblico e politico.

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Abstract Maintaining organ homeostasis requires complex functional synergy between distinct cell types, a snapshot of which is glimpsed through the simultaneously broad and granular analysis provided by single-cell atlases. Knowledge of the transcriptional programs underpinning the complex and specialized functions of human kidney cell populations at homeostasis is limited by difficulty accessing healthy, fresh tissue. Here, we present a single-cell perspective of healthy human kidney from 19 living donors, with equal contribution from males and females, profiling the transcriptome of 27677 high-quality cells to map healthy kidney at high resolution. Our sex-balanced dataset revealed sex-based differences in gene expression within proximal tubular cells, specifically, increased anti-oxidant metallothionein genes in females and the predominance of aerobic metabolism-related genes in males. Functional differences in metabolism were confirmed between male and female proximal tubular cells, with male cells exhibiting higher oxidative phosphorylation and higher levels of energy precursor metabolites. Within the immune niche, we identified kidney-specific lymphocyte populations with unique transcriptional profiles indicative of kidney-adapted functions and validated findings by flow cytometry. We observed significant heterogeneity in resident myeloid populations and identified an MRC1+ LYVE1+ FOLR2+ C1QC+ population as the predominant myeloid population in healthy kidney. This study provides a detailed cellular map of healthy human kidney, revealing novel insights into the complexity of renal parenchymal cells and kidney-resident immune populations.

Abstract Next generation sequencing has become a common tool in the diagnosis of genetic diseases. However, for the vast majority of genetic variants that are discovered, a clinical interpretation is not available. Variant effect mapping allows the functional effects of many single amino acid variants to be characterized in parallel. Here, we combine multiplexed functional assays with machine learning to assess the effects of amino acid substitutions in the human intellectual disability-associated gene,GDI1. We show that the resulting variant effect map can be used to discriminate pathogenic from benign variants. Our variant effect map recovers known biochemical and structural features ofGDI1and reveals additional aspects ofGDI1function. We explore how our functional assays can aid in the interpretation of novelGDI1variants as they are discovered, and to re-classify previously observed variants of unknown significance.

Pastoral Counseling Department, Loyola University, Columbia, Maryland (Dr Wicks); College of Nursing and Health Professions, Drexel University, Philadelphia, Pennsylvania (Dr Donnelly). Correspondence: Robert Wicks, PsyD, Pastoral Counseling Department, Loyola University Maryland, 8890 McGaw Road, Columbia, MD 21045 ([email protected]). The authors have disclosed no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Alternative splicing generates multiple transcript and protein isoforms from the same gene and thus is important in gene expression regulation. To date, RNA-sequencing (RNA-seq) is the standard method for quantifying changes in alternative splicing on a genome-wide scale. Understanding the current limitations of RNA-seq is crucial for reliable analysis and the lack of high quality, comprehensive transcriptomes for most species, including model organisms such as Arabidopsis, is a major constraint in accurate quantification of transcript isoforms. To address this, we designed a novel pipeline with stringent filters and assembled a comprehensive Reference Transcript Dataset for Arabidopsis (AtRTD2) containing 82,190 non-redundant transcripts from 34 212 genes. Extensive experimental validation showed that AtRTD2 and its modified version, AtRTD2-QUASI, for use in Quantification of Alternatively Spliced Isoforms, outperform other available transcriptomes in RNA-seq analysis. This strategy can be implemented in other species to build a pipeline for transcript-level expression and alternative splicing analyses.

Background: Spontaneous intracerebral hemorrhage (sICH) is associated with substantial disability, accounting for considerable resource utilization among stroke survivors. Debate exists about the timing and utilization of tracheostomy (Trach) and percutaneous gastrostomy (PEG) tube placement in sICH patients. We hypothesized that sICH survivors with PEG and/or Trach would have higher odds of 30-day readmission. Methods: We analyzed the 2013 Nationwide Readmissions Database, a nationally representative sample of hospital discharges. Patients with a primary discharge diagnosis of sICH (ICD-9 code 431) were included in the analysis. Repeat, pediatric, same-day events, head trauma, AVM/fistula, and discharges occurring in December were excluded. Patients who received PEG and/or Trach were identified using published algorithms. We defined readmission as any admission within 30-days of index hospitalization discharge. Odds ratios for 30-day readmission comparing exposed versus unexposed were estimated with adjustment for demographics, risk factors, and concurrent illness. All analyses were performed using survey design variables. Results: Among the 32,715 sICH index hospitalizations, 3,480 (10.6%) received a PEG and 1806 (5.5%) received a Trach. Overall 4,320 (13.2%) were readmitted within 30 days (PEG 20.5%, trach 18.9%). In the fully adjusted models, sICH patients with PEG had higher odds of readmission (OR 1.43, 95% CI 1.14-1.80), while patients with trach did not (OR 0.77, 95% CI 0.54-1.11). Predictors of readmission among individuals with and without PEG and Trach will be presented. Conclusions: sICH patients who underwent PEG placement had higher odds of 30-day readmission while patients receiving Trach did not. This finding suggests that heightened post-discharge surveillance of individuals receiving PEG may be warranted.

Hamilton, Cindy W. PHARMD, ELS; Donnelly, Julia PHD, BPHARM, MRPHARMS; Gertel, Art MS; Marchington, Jackie PHD, CMPP; Woolley, Karen PHD, CMPP Author Information

Cerium oxide nanoparticles (Nanoceria) have shown promise as catalytic antioxidants in the test tube, cell culture models and animal models of disease. However given the reactivity that is well established at the surface of these nanoparticles, the biological utilization of Nanoceria as a therapeutic still poses many challenges. Moreover the form that these particles take in a biological environment, such as the changes that can occur due to a protein corona, are not well established. This review aims to summarize the existing literature on biological use of Nanoceria, and to raise questions about what further study is needed to apply this interesting catalytic material to biomedical applications. These questions include: 1) How does preparation, exposure dose, route and experimental model influence the reported effects of Nanoceria in animal studies? 2) What are the considerations to develop Nanoceria as a therapeutic agent in regards to these parameters? 3) What biological targets of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are relevant to this targeting, and how do these properties also influence the safety of these nanomaterials?