The PPARγ Agonist Rosiglitazone Suppresses Syngeneic Mouse SCC (Squamous Cell Carcinoma) Tumor Growth through an Immune-Mediated Mechanism

Recent evidence suggests that PPARγ agonists may promote anti-tumor immunity. We show that immunogenic PDV cutaneous squamous cell carcinoma (CSCC) tumors are rejected when injected intradermally at a low cell number (1 × 106) into immune competent syngeneic hosts, but not immune deficient mice. At higher cell numbers (5 × 106 PDV cells), progressively growing tumors were established in 14 of 15 vehicle treated mice while treatment of mice with the PPARγ agonist rosiglitazone resulted in increased tumor rejection (5 of 14 tumors), a significant decrease in PDV tumor size, and a significant decrease in tumor cell Ki67 labeling. Rosiglitazone treatment had no effect on tumor rejection, tumor volume or PDV tumor cell proliferation in immune deficient NOD.CB17-PrkdcSCID/J mice. Rosiglitazone treatment also promoted an increase in tumor infiltrating CD3+ T-cells at both early and late time points. In contrast, rosiglitazone treatment had no significant effect on myeloid cells expressing either CD11b or Gr-1 but suppressed a late accumulation of myeloid cells expressing both CD11b and Gr-1, suggesting a potential role for CD11b+Gr-1+ myeloid cells in the late anti-tumor immune response. Overall, our data provides evidence that the PPARγ agonist rosiglitazone promotes immune-mediated anti-neoplastic activity against tumors derived from this immunogenic CSCC cell line

Best Practices for Staff Sharing

Medium to larger academic libraries often hire and train staff members to perform a variety of duties within a single department. However, in the current difficult budgetary environment, such academic libraries may use sharing of staff members between departments and cross-training in order to maintain the provision of high quality library service. This poster session will present a set of best practices for staff sharing, including scheduling and prioritizing tasks, as well as the advantages and disadvantages of such sharing from the perspectives of the supervisors and staff members. Examples of staff sharing as implemented at Booth Library, Eastern Illinois University will also be provided

Getting the Most Out of Your Student Worker Budget: A Survey of Tasks Performed by Student Assistants in Access Services Departments

University libraries invest considerable funds and staff time in the hiring, training, and employment of student assistants. Access Services departments within university libraries depend on student assistants to complete tasks and aid in the work flow in virtually all areas of the department. With the recent increases in minimum wage and uncertain library budgets, the need for the most efficient and effective use of student assistants has become an even greater concern. This poster session will present the results of a recently conducted survey of Access Services department supervisors on the hiring, training, and duties assigned to student assistants. Results of the survey will present new ideas and approaches that other libraries have employed on how to best make use of student assistants

Interlibrary Loan Patron Use Patterns: An Examination of Borrowing Requests at a Mid-sized Academic Library

The results of a recently conducted study of interlibrary loan fee-based borrowing requests are presented in this article. The study examined 3,074 borrowing requests completed over a three-year period from January 2007 to December 2009. An analysis of the statistics was made to determine patron behavior in submitting requests and the types of materials being requested

Getting the Most Out of Your Student Worker Budget: A Survey of Tasks Performed by Student Assistants in Access Services Departments

University libraries invest considerable funds and staff time in the hiring, training, and employment of student assistants. Access Services departments within university libraries depend on student assistants to complete tasks and aid in the work flow in virtually all areas of the department. With the recent increases in minimum wage and uncertain library budgets, the need for the most efficient and effective use of student assistants has become an even greater concern. This poster session will present the results of a recently conducted survey of Access Services department supervisors on the hiring, training, and duties assigned to student assistants. Results of the survey will present new ideas and approaches that other libraries have employed on how to best make use of student assistants

Valence and magnetic instabilities in Sm compounds at high pressures

We report on the study of the response to high pressures of the electronic and magnetic properties of several Sm-based compounds, which span at ambient pressure the whole range of stable charge states between the divalent and the trivalent. Our nuclear forward scattering of synchrotron radiation and specific heat investigations show that in both golden SmS and SmB6 the pressure-induced insulator to metal transitions (at 2 and about 4-7 GPa, respectively) are associated with the onset of long-range magnetic order, stable up to at least 19 and 26 GPa, respectively. This long-range magnetic order, which is characteristic of Sm(3+), appears already for a Sm valence near 2.7. Contrary to these compounds, metallic Sm, which is trivalent at ambient pressure, undergoes a series of pressure-induced structural phase transitions which are associated with a progressive decrease of the ordered 4f moment.Comment: 15 pages (including 7 figures) submitted to J. Phys.: Condens. Matte

Epidermal PPARγ influences subcutaneous tumor growth and acts through TNF-α to regulate contact hypersensitivity and the acute photoresponse

It is known that ultraviolet B (UVB) induces PPARγ ligand formation while loss of murine epidermal PPARγ (Pparg-/-epi) promotes UVB-induced apoptosis, inflammation, and carcinogenesis. PPARγ is known to suppress tumor necrosis factor-α (TNF-α) production. TNF-α is also known to promote UVB-induced inflammation, apoptosis, and immunosuppression. We show that Pparg-/-epi mice exhibit increased baseline TNF-α expression. Neutralizing Abs to TNF-α block the increased photo-inflammation and photo-toxicity that is observed in Pparg-/-epi mouse skin. Interestingly, the increase in UVB-induced apoptosis in Pparg-/-epi mice is not accompanied by a change in cyclobutane pyrimidine dimer clearance or in mutation burden. This suggests that loss of epidermal PPARγ does not result in a significant alteration in DNA repair capacity. However, loss of epidermal PPARγ results in marked immunosuppression using a contact hypersensitivity (CHS) model. This impaired CHS response was significantly alleviated using neutralizing TNF-α antibodies or loss of germline Tnf. In addition, the PPARγ agonist rosiglitazone reversed UVB-induced systemic immunosuppression (UV-IS) as well as UV-induced growth of B16F10 melanoma tumor cells in syngeneic mice. Finally, increased B16F10 tumor growth was observed when injected subcutaneously into Pparg-/-epi mice. Thus, we provide novel evidence that epidermal PPARγ is important for cutaneous immune function and the acute photoresponse

Human nasal wash RNA-Seq reveals distinct cell-specific innate immune responses in influenza versus SARS-CoV-2

BACKGROUND Influenza A virus (IAV) and SARS-CoV-2 are pandemic viruses causing millions of deaths, yet their clinical manifestations are distinctly different. METHODS With the hypothesis that upper airway immune and epithelial cell responses are also distinct, we performed single-cell RNA sequencing (scRNA-Seq) on nasal wash cells freshly collected from adults with either acute COVID-19 or influenza or from healthy controls. We focused on major cell types and subtypes in a subset of donor samples. Results Nasal wash cells were enriched for macrophages and neutrophils for both individuals with influenza and those with COVID-19 compared with healthy controls. Hillock-like epithelial cells, M2-like macrophages, and age-dependent B cells were enriched in COVID-19 samples. A global decrease in IFN-associated transcripts in neutrophils, macrophages, and epithelial cells was apparent in COVID-19 samples compared with influenza samples. The innate immune response to SARS-CoV-2 appears to be maintained in macrophages, despite evidence for limited epithelial cell immune sensing. Cell-to-cell interaction analyses revealed a decrease in epithelial cell interactions in COVID-19 and highlighted differences in macrophage-macrophage interactions for COVID-19 and influenza. Conclusions Our study demonstrates that scRNA-Seq can define host and viral transcriptional activity at the site of infection and reveal distinct local epithelial and immune cell responses for COVID-19 and influenza that may contribute to their divergent disease courses. Funding Massachusetts Consortium on Pathogen Readiness, the Mathers Foundation, and the Department of Defense (W81XWH2110029) COVID-19 Expansion for AIRe Program

Type I IFN-Driven Immune Cell Dysregulation in Rat Autoimmune Diabetes

Type 1 diabetes is a chronic autoimmune disease, characterized by the immune-mediated destruction of insulin-producing beta cells of pancreatic islets. Essential components of the innate immune antiviral response, including type I IFN and IFN receptor (IFNAR)-mediated signaling pathways, likely contribute to human type 1 diabetes susceptibility. We previously showed that LEW.1WR1 Ifnar1 (-/-) rats have a significant reduction in diabetes frequency following Kilham rat virus (KRV) infection. To delineate the impact of IFNAR loss on immune cell populations in KRV-induced diabetes, we performed flow cytometric analysis in spleens from LEW.1WR1 wild-type (WT) and Ifnar1 (-/-) rats after viral infection but before the onset of insulitis and diabetes. We found a relative decrease in CD8(+) T cells and NK cells in KRV-infected LEW.1WR1 Ifnar1 (-/-) rats compared with KRV-infected WT rats; splenic regulatory T cells were diminished in WT but not Ifnar1 (-/-) rats. In contrast, splenic neutrophils were increased in KRV-infected Ifnar1 (-/-) rats compared with KRV-infected WT rats. Transcriptional analysis of splenic cells from KRV-infected rats confirmed a reduction in IFN-stimulated genes in Ifnar1 (-/-) compared with WT rats and revealed an increase in transcripts related to neutrophil chemotaxis and MHC class II. Single-cell RNA sequencing confirmed that MHC class II transcripts are increased in monocytes and macrophages and that numerous types of splenic cells harbor KRV. Collectively, these findings identify dynamic shifts in innate and adaptive immune cells following IFNAR disruption in a rat model of autoimmune diabetes, providing insights toward the role of type I IFNs in autoimmunity