A Helminth-Derived Chitinase Structurally Similar to Mammalian Chitinase Displays Immunomodulatory Properties in Inflammatory Lung Disease

The authors gratefully thank Marion Müller, Christiane Palissa, Yvonne Weber, Bettina Sonnenburg, and Beate Anders for the excellent technical assistance and Franziska Rohr for her help within the animal facility. We also thank Prof. Judith E. Allen for her expertise, critical advice, and intellectual discussion of the topic.Peer reviewe

A Helminth Derived Chitinase Structurally Similar to Mammalian Chitinase Displays Immunomodulatory Properties in Inflammatory Lung Disease

Immunomodulation of airway hyperreactivity by excretory secretory ES products of the first larval stage L1 of the gastrointestinal nematode Trichuris suis is reported by us and others. Here, we aimed to identify the proteins accounting for the modulatory effects of the T. suis L1 ES proteins and studied six selected T. suis L1 proteins for their immunomodulatory efficacy in a murine OVA induced allergic airway disease model. In particular, an enzymatically active T. suis chitinase mediated amelioration of clinical signs of airway hyperreactivity, primarily associated with suppression of eosinophil recruitment into the lung, the associated chemokines, and increased numbers of RELM amp; 945; interstitial lung macrophages. While there is no indication of T. suis chitinase directly interfering with dendritic cell activation or antigen presentation to CD4 T cells, treatment of allergic mice with the worm chitinase influenced the hosts own chitinase activity in the inflamed lung. The three dimensional structure of the T. suis chitinase as determined by high resolution X ray crystallography revealed high similarities to mouse acidic mammalian chitinase AMCase but a unique ability of T. suis chitinase to form dimers. Our data indicate that the structural similarities between the parasite and host chitinase contribute to the disease ameliorating effect of the helminth derived chitinase on allergic lung inflammatio

Elasticity and Petri nets

Digital electronic systems typically use synchronous clocks and primarily assume fixed duration of their operations to simplify the design process. Time elastic systems can be constructed either by replacing the clock with communication handshakes (asynchronous version) or by augmenting the clock with a synchronous version of a handshake (synchronous version). Time elastic systems can tolerate static and dynamic changes in delays (asynchronous case) or latencies (synchronous case) of operations that can be used for modularity, ease of reuse and better power-delay trade-off. This paper describes methods for the modeling, performance analysis and optimization of elastic systems using Marked Graphs and their extensions capable of describing behavior with early evaluation. The paper uses synchronous elastic systems (aka latency-tolerant systems) for illustrating the use of Petri nets, however, most of the methods can be applied without changes (except changing the delay model associated with events of the system) to asynchronous elastic systems.Peer ReviewedPostprint (author's final draft

A patient-derived explant (PDE) model of hormone-dependent cancer

Breast and prostate cancer research to date has largely been predicated on the use of cell lines in vitro or in vivo. These limitations have led to the development of more clinically relevant models, such as organoids or murine xenografts that utilize patient-derived material; however, issues related to low take rate, long duration of establishment, and the associated costs constrain use of these models. This study demonstrates that ex vivo culture of freshly resected breast and prostate tumor specimens obtained from surgery, termed patient-derived explants (PDEs), provides a high-throughput and cost-effective model that retains the native tissue architecture, microenvironment, cell viability, and key oncogenic drivers. The PDE model provides a unique approach for direct evaluation of drug responses on an individual patient's tumor, which is amenable to analysis using contemporary genomic technologies. The ability to rapidly evaluate drug efficacy in patient-derived material has high potential to facilitate implementation of personalized medicine approaches.Margaret M. Centenera, Theresa E. Hickey, Shalini Jindal, Natalie K. Ryan, Preethi Ravindranathan, Hisham Mohammed, Jessica L. Robinson, Matthew J. Schiewer, Shihong Ma, Payal Kapur, Peter D. Sutherland, Clive E. Hoffmann, Claus G. Roehrborn, Leonard G. Gomella, Jason S. Carroll, Stephen N. Birrell, Karen E. Knudsen, Ganesh V. Raj, Lisa M. Butler, Wayne D. Tille

What Physical Processes Drive the Interstellar Medium in the Local Bubble?

Recent 3D high-resolution simulations of the interstellar medium in a star form- ing galaxy like the Milky Way show that supernova explosions are the main driver of the structure and evolution of the gas. Its physical state is largely controlled by turbulence due to the high Reynolds numbers of the average flows. For a constant supernova rate a dynam- ical equilibrium is established within 200 Myr of simulation as a consequence of the setup of a galactic fountain. The resulting interstellar medium reveals a typical density/pressure pattern, i.e. distribution of so-called gas phases, on scales of 500–700 pc, with interstellar bubbles being a common phenomenon just like the Local Bubble and the Loop I superbub- ble, which are assumed to be interacting. However, modeling the Local Bubble is special, because it is driven by a moving group, passing through its volume, as it is inferred from the analysis of Hipparcos data. A detailed analysis reveals that between 14 and 19 super- novae have exploded during the last 15 Myr. The age of the Local Bubble is derived from comparison with HI and UV absorption line data to be 14.5±0.7 Myr. We further predict the 0.4merging of the two bubbles in about 3 Myr from now, when the interaction shell starts to fragment. The Local Cloud and its companion HI clouds are the consequence of a dynamical instability in the interaction shell between the Local and the Loop I bubble

The Psychological Science Accelerator’s COVID-19 rapid-response dataset

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data