Alternative Dispute Resolution in U.S. Bankruptcy Practice

The use of ADR in bankruptcy cases, while firmly established in concept across the nation, has been realized in a minority of jurisdictions. Mediation training of judges, lawyers and professionals of other disciplines, together with the continued development of ADR programs, is necessary to achieve the vision of a judicial system in which both adjudicative and non-adjudicative, or negotiative, dispute resolution services are available to all parties in all cases

Defects in intracellular trafficking of fungal cell wall synthases lead to aberrant host immune recognition

Acknowledgments We acknowledge Jeanette Wagener and Louise Walker for performing the HPAEC-PAD analysis and Neil Gow for providing access to the Dionex HPAEC-PAD instrumentation. We thank Mike Cook and the Duke University Cancer Center Flow Cytometry Shared Resource for assistance with the flow cytometry. We also acknowledge Michelle Plue and the Duke University Shared Materials Institute Facility for performing the transmission electron microscopy. We thank Marcel Wu¨thrich for providing the MyD88-/-and TLR2/4-/- mice, and Mari Shinohara and Elizabeth Deerhake for providing the Dectin-1-/- mice. Funding: These experiments were supported by a National Institutes of Health grant awarded to JAA and FLW, Jr. (R01 AI074677, https://grants.nih.gov/grants/oer.html). CM and colleagues Jeanette Wagener, Louise Walker, Neil Gow were supported by the Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377, https://wellcome.ac.uk), Wellcome Trust Senior Investigator Award (101873) and the MRC Centre for Medical Mycology (MR/N006364/1, https://www.abdn.ac.uk/cmm/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Cholesterol and Lipoprotein Dynamics in a Hibernating Mammal

Hibernating mammals cease feeding during the winter and rely primarily on stored lipids to fuel alternating periods of torpor and arousal. How hibernators manage large fluxes of lipids and sterols over the annual hibernation cycle is poorly understood. The aim of this study was to investigate lipid and cholesterol transport and storage in ground squirrels studied in spring, summer, and several hibernation states. Cholesterol levels in total plasma, HDL and LDL particles were elevated in hibernators compared with spring or summer squirrels. Hibernation increased plasma apolipoprotein A-I expression and HDL particle size. Expression of cholesterol 7 alpha-hydroxylase was 13-fold lower in hibernators than in active season squirrels. Plasma triglycerides were reduced by fasting in spring but not summer squirrels. In hibernators plasma β-hydroxybutyrate was elevated during torpor whereas triglycerides were low relative to normothermic states. We conclude that the switch to a lipid-based metabolism during winter, coupled with reduced capacity to excrete cholesterol creates a closed system in which efficient use of lipoproteins is essential for survival

Candida-induced granulocytic myeloid-derived suppressor cells are protective against polymicrobial sepsis

ABSTRACT Polymicrobial intra-abdominal infections (IAI) can lead to life-threatening sepsis with significant morbidity and mortality, especially when pathogenic fungi are involved. We have employed an established clinically relevant mouse model of fungal/bacterial IAI and shown that immunization with low-virulence Candida species, that is, Candida dubliniensis, can induce responses that protect against sepsis via the suppression of lethal inflammation. This protection is dependent on long-lived Gr-1+ polymorphonuclear leukocytes that display characteristics consistent with myeloid-derived suppressor cells (MDSCs) and trained innate immunity. Here we aimed to functionally and phenotypically characterize these protective Gr-1+ leukocytes. Compared to nonimmunized control mice, we observed increased levels of CD11b+ Gr-1+ cells systemically and locally in the peritoneal cavity of immunized mice. Isolated peritoneal Gr-1+ cells displayed hallmark MDSC phenotypes including increased T-cell suppressor activity and increased MDSC effector activity. Furthermore, we observed increased levels of the anti-inflammatory MDSC cytokine interleukin (IL)-10 in the peritoneal cavity of immunized mice and, in contrast, increased inflammatory responses when Gr-1+ leukocytes were depleted from immunized mice prior to challenge. Flow cytometric analysis revealed that Ly6G+ granulocytic MDSCs (G-MDSCs) were preferentially increased over Ly6C+ monocytic MDSCs (M-MDSCs) in immunized mice. Importantly, G-MDSCs, but not M-MDSCs, as well as IL-10 production, are required for full protection against lethal sepsis. From these data, we conclude that the Gr-1+ leukocytes that protect against polymicrobial sepsis are bona fide MDSCs and hypothesize that the mechanism of MDSC-mediated protection includes abrogation of lethal inflammation by IL-10. IMPORTANCE Polymicrobial intra-abdominal infections are serious clinical infections that can lead to life-threatening sepsis, which is difficult to treat in part due to the complex and dynamic inflammatory responses involved. Our prior studies demonstrated that immunization with low-virulence Candida species can provide strong protection against lethal polymicrobial sepsis challenge in mice. This long-lived protection was found to be mediated by trained Gr-1+ polymorphonuclear leukocytes with features resembling myeloid-derived suppressor cells (MDSCs). Here we definitively characterize these cells as MDSCs and demonstrate that their mechanism of protection involves the abrogation of lethal inflammation, in part through the action of the anti-inflammatory cytokine interleukin (IL)-10. These studies highlight the role of MDSCs and IL-10 in controlling acute lethal inflammation and give support for the utility of trained tolerogenic immune responses in the clinical treatment of sepsis