Examining Doctoral Student Education for Collaborative Authorship in LIS

Doctoral students in Library and Information Science (LIS) are encouraged to publish formally by themselves, but also with faculty and peer collaborators. Ethical practices for evaluating authorship contribution in collaborative research projects are not, however, generally included as a formal aspect of doctoral education. How, then, can LIS doctoral students best learn about the ethical enactment of co-authorship? This paper presents and synthesizes literature and standards on authorship collaborations relevant to doctoral students and their mentors, and makes three recommendations to supplement authorship education in the curriculum of LIS doctoral programs. Special attention is devoted to interdisciplinary collaborations

Modulation of Neutrophil Function by Recombinant Human IgG1 Fc Hexamer in the Endogenous K/BxN Mouse Model of Rheumatoid Arthritis.

INTRODUCTION Neutrophils are a pivotal cell type in the K/BxN mouse model of rheumatoid arthritis and play an essential role in the progression of the arthritis. They are readily activated by immune complexes (ICs) via their FcγRs to release IL-1β in addition to other cytokines, which are inducing cartilage destruction. Neutrophils also release neutrophil-active chemokines to recruit themselves in an autocrine manner to perpetuate tissue destruction. FcγR-expression on neutrophils is of crucial importance for the recognition of ICs. METHODS In this study, due to its high avidity for binding to FcγRs, we investigated the potential anti-inflammatory effect of a recombinant IgG1 Fc hexamer (rFc-µTP-L309C) on neutrophils in the K/BxN mouse model of endogenously generated chronic arthritis. 200 mg/kg rFc-µTP-L309C and human serum albumin (HSA), used as controls, were administered subcutaneously every other day. Mouse ankle joints were monitored daily to generate a clinical score. Immunohistology was used to evaluate neutrophil infiltration and TUNEL to assess apoptosis. ELISA was used to measure IL-1β. RESULTS Treatment with rFc-µTP-L309C, but not HSA, was able to significantly ameliorate the arthritis in the K/BxN mice. Significant neutrophil infiltration into the ankle joint was found, but treatment with rFc-µTP-L309C resulted in significantly less neutrophil infiltration. There was no significant influence of rFc-µTP-L309C on neutrophil death or apoptosis. Less neutrophil infiltration could not be correlated to chemokine-mediated migration. Significantly less IL-1β was measured in mice treated with rFc-µTP-L309C. CONCLUSION In the endogenous K/BxN mouse model of rheumatoid arthritis, amelioration can be explained in part by inhibition of neutrophil infiltration into the joints as well as inhibition of IL-1β production. Given the observed inhibitory properties on neutrophils, rFc-µTP-L309C may be a potential therapeutic candidate to treat autoimmune and inflammatory conditions in which neutrophils are the predominant cell type involved in pathogenesis

Beta-Catenin Signaling Plays a Disparate Role in Different Phases of Fracture Repair: Implications for Therapy to Improve Bone Healing

In a study in mice Benjamin Alman and colleagues show that β-catenin functions differently in different stages of fracture repair; moreover, activation of β-catenin by lithium improves fracture healing when used in later phases of repair

T-Lymphocytes Enable Osteoblast Maturation via IL-17F during the Early Phase of Fracture Repair

While it is well known that the presence of lymphocytes and cytokines are important for fracture healing, the exact role of the various cytokines expressed by cells of the immune system on osteoblast biology remains unclear. To study the role of inflammatory cytokines in fracture repair, we studied tibial bone healing in wild-type and Rag1−/− mice. Histological analysis, µCT stereology, biomechanical testing, calcein staining and quantitative RNA gene expression studies were performed on healing tibial fractures. These data provide support for Rag1−/− mice as a model of impaired fracture healing compared to wild-type. Moreover, the pro-inflammatory cytokine, IL-17F, was found to be a key mediator in the cellular response of the immune system in osteogenesis. In vitro studies showed that IL-17F alone stimulated osteoblast maturation. We propose a model in which the Th17 subset of T-lymphocytes produces IL-17F to stimulate bone healing. This is a pivotal link in advancing our current understanding of the molecular and cellular basis of fracture healing, which in turn may aid in optimizing fracture management and in the treatment of impaired bone healing

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Design of an Extension to Punto Verde Environmental Theme Park

This report recommends a design plan for an extension to the Punto Verde environmental theme park. We analyzed the extension site, designed educational attractions, produced a site layout, and generated an itemized construction budget. The extension we designed encourages children to become better citizens by promoting environmental and social education through interaction, discovery, challenge, adventure, creativity, and sociability. Our recommendations promote appreciation of nature, social responsibility, and environmental awareness in visitors, inspiring them to be positive stewards of the environment

IL-17F promotes osteoblast maturation.

<p>(<b>A</b>) Treatment of MC3T3-E1 pre-osteoblast cell line cultures directly with pro-inflammatory cytokine IL-17F showed increased bone marker gene expression of Col1, Col2, BSP and osteocalcin, whereas, anti-inflammatory cytokine TGFβ treatment inhibited osteoblast maturation and showed significant decreases in expression of the entire panel of bone markers analyzed. (<b>B</b>) Left: Treatment of <i>Rag1^−/−</i> mice primary mesenchymal stromal cell cultures directly with pro-inflammatory cytokine IL-17F showed increased bone marker gene expression of Col1, Col2, and Runx2. Right: In contrast, treatment with anti-inflammatory cytokine TGFβ inhibited WT mice primary mesenchymal stromal cell maturation and showed significant decreases in expression of all the bone markers analyzed. (*p<0.05 and **p<0.01).</p

Healing of the fracture callus in <i>Rag1</i>

<p><i>⁻</i>^{<b><i>/</i></b><i>−</i>}<b>mice is delayed.</b> (<b>A</b>) Safranin O staining of WT and <i>Rag1^−/−</i> mice 28 days post fracture showed persistence of a cartilage template with more proteoglycan staining (black arrows) and less bridging bone across the fracture gap in <i>Rag1^−/−</i> compared to WT mice. (<b>B</b>) µCT analysis confirmed the presence of a wider, lower density callus in <i>Rag1^−/−</i> mice tibias at 28 days. (<b>C</b>) This was reflected by increased total callus volume (TV) measurements (p = 0.002) and decreased tissue mineral density (TMD) at 28 days in the <i>Rag1^−/−</i> compared to WT mice (p = 0.004). Torsional rigidity (TR) was significantly higher in <i>Rag1^−/−</i> mice compared to WT (p = 0.002). (<b>D</b>) Mechanical assessment of the samples using torsional mechanical testing showed a significantly higher ultimate torque and torsional stiffness in the <i>Rag1^−/−</i> mice at 28 days compared to WT (p = 0.002).</p

Osteogenesis is reduced in <i>Rag1</i>

<p><i>⁻</i>^{<b><i>/</i></b><i>−</i>}<b>mice during fracture repair.</b> (<b>A</b>) <i>In vitro</i> cultures of primary mesenchymal stromal cells differentiated to osteoblast colony-forming units (CFU) showed lower gene expression levels of bone markers Col1, Col2 and BSP and osteocalcin in <i>Rag1^−/−</i> mice compared to WT. *p<0.05, **p<0.01 (n = 10). (<b>B</b>) Alizarin red staining of osteoblast CFU showed significant decrease in mineralization at 20 days of culture in <i>Rag1^−/−</i> compared to WT. CFU-osteoblast was quantified by direct counting of all stained nodules positive to Alizarin Red using light microscopy. (<b>C</b>) Digital fluorescent microscopy images of calcein green administered mice 2 and 9 days prior to harvest at 21 and 28 days post fracture exhibited a smaller distance measured between mineralization fronts and hence, less bone formation in <i>Rag1^−/−</i> compared to WT mice (p<0.05). Unfractured limbs showed no significant differences in bone formation.</p

Proposed mechanistic scheme of T-cell mediated osteoblast differentiation and maturation.

<p>Upstream IL-6 increase early post fracture promotes naïve CD4+ T-cells to Th17 cells stimulating pre-osteoblast cell differentiation via IL-17F. Concomitantly, the Treg pathway is suppressed, decreasing TGFβ and IL-10 and inhibiting pre-osteoblast differentiation. The effect of IL-6 also has a direct role in the later stages of osteoblast differentiation in fracture healing.</p