232 research outputs found
Probing the luminal microenvironment of reconstituted epithelial microtissues.
Polymeric microparticles can serve as carriers or sensors to instruct or characterize tissue biology. However, incorporating microparticles into tissues for in vitro assays remains a challenge. We exploit three-dimensional cell-patterning technologies and directed epithelial self-organization to deliver microparticles to the lumen of reconstituted human intestinal microtissues. We also develop a novel pH-sensitive microsensor that can measure the luminal pH of reconstituted epithelial microtissues. These studies offer a novel approach for investigating luminal microenvironments and drug-delivery across epithelial barriers
A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity
Developing tissues contain motile populations of cells that can self-organize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. The ducts and acini of the human mammary gland are prototypical heterogeneous and dynamic tissues comprising two concentrically arranged cell types. To investigate the consequences of cellular heterogeneity and plasticity on cell positioning in the mammary gland, we reconstituted its self-organization from aggregates of primary cells in vitro. We find that self-organization is dominated by the interfacial energy of the tissue–ECM boundary, rather than by differential homo- and heterotypic energies of cell–cell interaction. Surprisingly, interactions with the tissue–ECM boundary are binary, in that only one cell type interacts appreciably with the boundary. Using mathematical modeling and cell-type-specific knockdown of key regulators of cell–cell cohesion, we show that this strategy of self-organization is robust to severe perturbations affecting cell–cell contact formation. We also find that this mechanism of self-organization is conserved in the human prostate. Therefore, a binary interfacial interaction with the tissue boundary provides a flexible and generalizable strategy for forming and maintaining the structure of two-component tissues that exhibit abundant heterogeneity and plasticity. Our model also predicts that mutations affecting binary cell–ECM interactions are catastrophic and could contribute to loss of tissue architecture in diseases such as breast cancer
Annihilation of low energy antiprotons in silicon
The goal of the AEIS experiment at the Antiproton
Decelerator (AD) at CERN, is to measure directly the Earth's gravitational
acceleration on antimatter. To achieve this goal, the AEIS
collaboration will produce a pulsed, cold (100 mK) antihydrogen beam with a
velocity of a few 100 m/s and measure the magnitude of the vertical deflection
of the beam from a straight path. The final position of the falling
antihydrogen will be detected by a position sensitive detector. This detector
will consist of an active silicon part, where the annihilations take place,
followed by an emulsion part. Together, they allow to achieve 1 precision on
the measurement of with about 600 reconstructed and time tagged
annihilations.
We present here, to the best of our knowledge, the first direct measurement
of antiproton annihilation in a segmented silicon sensor, the first step
towards designing a position sensitive silicon detector for the
AEIS experiment. We also present a first comparison with
Monte Carlo simulations (GEANT4) for antiproton energies below 5 MeVComment: 21 pages in total, 29 figures, 3 table
Prospects for measuring the gravitational free-fall of antihydrogen with emulsion detectors
The main goal of the AEgIS experiment at CERN is to test the weak equivalence
principle for antimatter. AEgIS will measure the free-fall of an antihydrogen
beam traversing a moir\'e deflectometer. The goal is to determine the
gravitational acceleration g for antihydrogen with an initial relative accuracy
of 1% by using an emulsion detector combined with a silicon micro-strip
detector to measure the time of flight. Nuclear emulsions can measure the
annihilation vertex of antihydrogen atoms with a precision of about 1 - 2
microns r.m.s. We present here results for emulsion detectors operated in
vacuum using low energy antiprotons from the CERN antiproton decelerator. We
compare with Monte Carlo simulations, and discuss the impact on the AEgIS
project.Comment: 20 pages, 16 figures, 3 table
Opportunities for organoids as new models of aging.
The biology of aging is challenging to study, particularly in humans. As a result, model organisms are used to approximate the physiological context of aging in humans. However, the best model organisms remain expensive and time-consuming to use. More importantly, they may not reflect directly on the process of aging in people. Human cell culture provides an alternative, but many functional signs of aging occur at the level of tissues rather than cells and are therefore not readily apparent in traditional cell culture models. Organoids have the potential to effectively balance between the strengths and weaknesses of traditional models of aging. They have sufficient complexity to capture relevant signs of aging at the molecular, cellular, and tissue levels, while presenting an experimentally tractable alternative to animal studies. Organoid systems have been developed to model many human tissues and diseases. Here we provide a perspective on the potential for organoids to serve as models for aging and describe how current organoid techniques could be applied to aging research
A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity
Developing tissues contain motile populations of cells that can self-organize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. The ducts and acini of the human mammary gland are prototypical heterogeneous and dynamic tissues comprising two concentrically arranged cell types. To investigate the consequences of cellular heterogeneity and plasticity on cell positioning in the mammary gland, we reconstituted its self-organization from aggregates of primary cells in vitro. We find that self-organization is dominated by the interfacial energy of the tissue–ECM boundary, rather than by differential homo- and heterotypic energies of cell–cell interaction. Surprisingly, interactions with the tissue–ECM boundary are binary, in that only one cell type interacts appreciably with the boundary. Using mathematical modeling and cell-type-specific knockdown of key regulators of cell–cell cohesion, we show that this strategy of self-organization is robust to severe perturbations affecting cell–cell contact formation. We also find that this mechanism of self-organization is conserved in the human prostate. Therefore, a binary interfacial interaction with the tissue boundary provides a flexible and generalizable strategy for forming and maintaining the structure of two-component tissues that exhibit abundant heterogeneity and plasticity. Our model also predicts that mutations affecting binary cell–ECM interactions are catastrophic and could contribute to loss of tissue architecture in diseases such as breast cancer
IODP workshop: Core-Log Seismic Investigation at Sea – Integrating legacy data to address outstanding research questions in the Nankai Trough Seismogenic Zone Experiment
The first International Ocean Discovery Program (IODP) Core-Log-Seismic
Integration at Sea (CLSI@Sea) workshop, held in January–February 2018,
brought together an international, multidisciplinary team of 14 early-career
scientists and a group of scientific mentors specialized in subduction zone
processes at the Nankai Trough, one of the Earth's most active
plate-subduction zones located off the southwestern coast of Japan. The goal
of the workshop was to leverage existing core, log, and seismic data
previously acquired during the IODP's Nankai Trough Seismogenic Zone
Experiment (NanTroSEIZE), to address the role of the deformation front of the
Nankai accretionary prism in tsunamigenic earthquakes and slow slip in the
shallow portion of the subduction interface. The CLSI@Sea workshop was
organized onboard the D/V Chikyu concurrently with IODP Expedition
380, allowing workshop participants to interact with expedition scientists
installing a long-term borehole monitoring system (LTBMS) at a site where the
workshop's research was focused. Sedimentary cores from across the
deformation front were brought onboard Chikyu, where they were made
available for new description, sampling, and analysis. Logging data, drilling
parameters, and seismic data were also available for investigation by
workshop participants, who were granted access to Chikyu laboratory
facilities and software to perform analyses at sea.Multi-thematic presentations facilitated knowledge transfer between the
participants across field areas, and highlighted the value of
multi-disciplinary collaboration that integrates processes across different
spatiotemporal scales. The workshop resulted in the synthesis of existing
geophysical, geologic, and geochemical data spanning IODP Sites C0006,
C0007, C0011 and C0012 in the NanTroSEIZE area, the identification of key
outstanding research questions in the field of shallow subduction zone
seismogenesis, and fostered collaborative and individual research plans
integrating new data analysis techniques and multidisciplinary approaches.</p
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