A Family of Diverse Kunitz Inhibitors from Echinococcus granulosus Potentially Involved in Host-Parasite Cross-Talk

The cestode Echinococcus granulosus, the agent of hydatidosis/echinococcosis, is remarkably well adapted to its definitive host. However, the molecular mechanisms underlying the successful establishment of larval worms (protoscoleces) in the dog duodenum are unknown. With the aim of identifying molecules participating in the E. granulosus-dog cross-talk, we surveyed the transcriptomes of protoscoleces and protoscoleces treated with pepsin at pH 2. This analysis identified a multigene family of secreted monodomain Kunitz proteins associated mostly with pepsin/H+-treated worms, suggesting that they play a role at the onset of infection. We present the relevant molecular features of eight members of the E. granulosus Kunitz family (EgKU-1 – EgKU-8). Although diverse, the family includes three pairs of close paralogs (EgKU-1/EgKU-4; EgKU-3/EgKU-8; EgKU-6/EgKU-7), which would be the products of recent gene duplications. In addition, we describe the purification of EgKU-1 and EgKU-8 from larval worms, and provide data indicating that some members of the family (notably, EgKU-3 and EgKU-8) are secreted by protoscoleces. Detailed kinetic studies with native EgKU-1 and EgKU-8 highlighted their functional diversity. Like most monodomain Kunitz proteins, EgKU-8 behaved as a slow, tight-binding inhibitor of serine proteases, with global inhibition constants (KI*) versus trypsins in the picomolar range. In sharp contrast, EgKU-1 did not inhibit any of the assayed peptidases. Interestingly, molecular modeling revealed structural elements associated with activity in Kunitz cation-channel blockers. We propose that this family of inhibitors has the potential to act at the E. granulosus-dog interface and interfere with host physiological processes at the initial stages of infection

Space-borne Bose-Einstein condensation for precision interferometry

Space offers virtually unlimited free-fall in gravity. Bose-Einstein condensation (BEC) enables ineffable low kinetic energies corresponding to pico- or even femtokelvins. The combination of both features makes atom interferometers with unprecedented sensitivity for inertial forces possible and opens a new era for quantum gas experiments. On January 23, 2017, we created Bose-Einstein condensates in space on the sounding rocket mission MAIUS-1 and conducted 110 experiments central to matter-wave interferometry. In particular, we have explored laser cooling and trapping in the presence of large accelerations as experienced during launch, and have studied the evolution, manipulation and interferometry employing Bragg scattering of BECs during the six-minute space flight. In this letter, we focus on the phase transition and the collective dynamics of BECs, whose impact is magnified by the extended free-fall time. Our experiments demonstrate a high reproducibility of the manipulation of BECs on the atom chip reflecting the exquisite control features and the robustness of our experiment. These properties are crucial to novel protocols for creating quantum matter with designed collective excitations at the lowest kinetic energy scales close to femtokelvins.Comment: 6 pages, 4 figure

Basement membrane components are key players in specialized extracellular matrices

More than three decades ago, basement membranes (BMs) were described as membrane-like structures capable of isolating a cell from and connecting a cell to its environment. Since this time, it has been revealed that BMs are specialized extracellular matrices (sECMs) with unique components that support important functions including differentiation, proliferation, migration, and chemotaxis of cells during development. The composition of these sECM is as unique as the tissues to which they are localized, opening the possibility that such matrices can fulfill distinct functions. Changes in BM composition play significant roles in facilitating the development of various diseases. Furthermore, tissues have to provide sECM for their stem cells during development and for their adult life. Here, we briefly review the latest research on these unique sECM and their components with a special emphasis on embryonic and adult stem cells and their niches

Structural basis of laminin binding to the LARGE glycans on dystroglycan

Dystroglycan is a highly glycosylated extracellular matrix receptor with essential functions in skeletal muscle and the nervous system. Reduced matrix binding by α-dystroglycan (α-DG) due to perturbed glycosylation is a pathological feature of several forms of muscular dystrophy. Like-acetylglucosaminyltransferase (LARGE) synthesizes the matrix-binding heteropolysaccharide [-glucuronic acid-β1,3-xylose- α1,3-]n. Using a dual exoglycosidase digestion, we confirm that this polysaccharide is present on native α-DG from skeletal muscle. The atomic details of matrix binding were revealed by a high-resolution crystal structure of laminin G-like (LG) domains 4-5 of laminin α2 bound to a LARGE-synthesized oligosaccharide. A single glucuronic acid- β1,3-xylose disaccharide repeat straddles a Ca2+ ion in the LG4 domain, with oxygen atoms from both sugars replacing Ca2+-bound water molecules. The chelating binding mode accounts for the high affinity of this protein-carbohydrate interaction. These results reveal a novel mechanism of carbohydrate recognition and provide a structural framework for elucidating the mechanisms underlying muscular dystrophy

Toward an Ethical Reflective Practice of a Theory in the Flesh: Embodied Subjectivities in a Youth Participatory Action Research Mural Project

The focus of this paper is to demonstrate how embodied subjectivities shape research experiences. Through an autoethnography of my involvement in a Youth Participatory Action Research (YPAR) after-school program with low-income and working-class youth of Color from predominantly Latinx communities I examined my embodied subjectivities, via an ethical reflective practice, as these surfaced in the research context. Autoethnography is presented as a tool to facilitate an ethical reflective practice that aligns with heart-centered work. Drawing from an epistemology of a theory in the flesh (Anzaldúa & Moraga, 1981), embodied subjectivities are defined by the lived experiences felt and expressed through the body, identities, and positionalities of the researcher. The article concludes with implications for the development of community psychology competencies that attend to the researcher\u27s embodied subjectivities

From Brazil with love: youth participation practice in Scotland

This chapter is based on a doctoral study that looked at youth participation practice in Scotland. It was driven by the belief that young people have the right to have a voice and should actively be involved in effecting change within their communities. The overall aim of the research was to gain insight into the lived experiences of young people who have taken part in youth participation projects, and to examine themes of social justice, empowerment and critical consciousness, empowerment and conscientisation. Paulo Freire’s (1996) theories and principles for transformative educational practice formed the theoretical framework for analysis of data

Space-borne Bose–Einstein condensation for precision interferometry

Owing to the low-gravity conditions in space, space-borne laboratories enable experiments with extended free-fall times. Because Bose–Einstein condensates have an extremely low expansion energy, space-borne atom interferometers based on Bose–Einstein condensation have the potential to have much greater sensitivity to inertial forces than do similar ground-based interferometers. On 23 January 2017, as part of the sounding-rocket mission MAIUS-1, we created Bose–Einstein condensates in space and conducted 110 experiments central to matter-wave interferometry, including laser cooling and trapping of atoms in the presence of the large accelerations experienced during launch. Here we report on experiments conducted during the six minutes of in-space flight in which we studied the phase transition from a thermal ensemble to a Bose–Einstein condensate and the collective dynamics of the resulting condensate. Our results provide insights into conducting cold-atom experiments in space, such as precision interferometry, and pave the way to miniaturizing cold-atom and photon-based quantum information concepts for satellite-based implementation. In addition, space-borne Bose–Einstein condensation opens up the possibility of quantum gas experiments in low-gravity conditions1,2

The modular X- and gamma-ray sensor (MXGS) of the ASIM Payload on the International Space Station

The Modular X- and Gamma-ray Sensor (MXGS) is an imaging and spectral X- and Gamma-ray instrument mounted on the starboard side of the Columbus module on the International Space Station. Together with the Modular Multi-Spectral Imaging Assembly (MMIA) (Chanrion et al. this issue) MXGS constitutes the instruments of the Atmosphere-Space Interactions Monitor (ASIM) (Neubert et al. this issue). The main objectives of MXGS are to image and measure the spectrum of X- and γ-rays from lightning discharges, known as Terrestrial Gamma-ray Flashes (TGFs), and for MMIA to image and perform high speed photometry of Transient Luminous Events (TLEs) and lightning discharges. With these two instruments specifically designed to explore the relation between electrical discharges, TLEs and TGFs, ASIM is the first mission of its kind. With an imaging system and a large detector area MXGS will, for the first time, allow estimation of the location of the source region and characterization of the energy spectrum of individual events. The sensors have fast readout electronics to minimize pileup effects, giving high time resolution of photon detection for comparison with measurements on μs-time scales of lightning processes measured by the MMIA and other sensors in space or on the ground. The detectors cover the large energy range of the relevant photon energies. In this paper we describe the scientific objectives, design, performance, imaging capabilities and operational modes of the MXGS instrument