911 research outputs found
A two-dimensional model of low-Reynolds number swimming beneath a free surface
Biological organisms swimming at low Reynolds number are often influenced by
the presence of rigid boundaries and soft interfaces. In this paper we present
an analysis of locomotion near a free surface with surface tension. Using a
simplified two-dimensional singularity model, and combining a complex variable
approach with conformal mapping techniques, we demonstrate that the deformation
of a free surface can be harnessed to produce steady locomotion parallel to the
interface. The crucial physical ingredient lies in the nonlinear hydrodynamic
coupling between the disturbance flow created by the swimmer and the free
boundary problem at the fluid surface
The Value of Comparative Animal Research : Krogh’s Principle Facilitates Scientific Discoveries
There are no conflicts of interest to declare. This paper developed from the 2016 Early Career Impact Award from the Federation of Associations in Behavioral & Brain Sciences to TJS. TJS has received funding from The Leverhulme Trust. FJPE is in receipt of funding from the BBSRC (BB/M001555/1). The National Institutes of Health has funded RDF (NS 034950, NS093277, NIMH 087930), AGO (HD079573, IOS-1354760) and AMK (HD081959). BAA is an Arnold O. Beckman postdoctoral fellow.Peer reviewedPostprin
Cellular aspect ratio and cell division mechanics underlie the patterning of cell progeny in diverse mammalian epithelia.
Cell division is essential to expand, shape, and replenish epithelia. In the adult small intestine, cells from a common progenitor intermix with other lineages, whereas cell progeny in many other epithelia form contiguous patches. The mechanisms that generate these distinct patterns of progeny are poorly understood. Using light sheet and confocal imaging of intestinal organoids, we show that lineages intersperse during cytokinesis, when elongated interphase cells insert between apically displaced daughters. Reducing the cellular aspect ratio to minimize the height difference between interphase and mitotic cells disrupts interspersion, producing contiguous patches. Cellular aspect ratio is similarly a key parameter for division-coupled interspersion in the early mouse embryo, suggesting that this physical mechanism for patterning progeny may pertain to many mammalian epithelia. Our results reveal that the process of cytokinesis in elongated mammalian epithelia allows lineages to intermix and that cellular aspect ratio is a critical modulator of the progeny pattern
LRH-1 mitigates intestinal inflammatory disease by maintaining epithelial homeostasis and cell survival.
Epithelial dysfunction and crypt destruction are defining features of inflammatory bowel disease (IBD). However, current IBD therapies targeting epithelial dysfunction are lacking. The nuclear receptor LRH-1 (NR5A2) is expressed in intestinal epithelium and thought to contribute to epithelial renewal. Here we show that LRH-1 maintains intestinal epithelial health and protects against inflammatory damage. Knocking out LRH-1 in murine intestinal organoids reduces Notch signaling, increases crypt cell death, distorts the cellular composition of the epithelium, and weakens the epithelial barrier. Human LRH-1 (hLRH-1) rescues epithelial integrity and when overexpressed, mitigates inflammatory damage in murine and human intestinal organoids, including those derived from IBD patients. Finally, hLRH-1 greatly reduces disease severity in T-cell-mediated murine colitis. Together with the failure of a ligand-incompetent hLRH-1 mutant to protect against TNFα-damage, these findings provide compelling evidence that hLRH-1 mediates epithelial homeostasis and is an attractive target for intestinal disease
Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche.
Epithelial surfaces form critical barriers to the outside world and are continuously renewed by adult stem cells1. Whereas dynamics of epithelial stem cells during homeostasis are increasingly well understood, how stem cells are redirected from a tissue-maintenance program to initiate repair after injury remains unclear. Here we examined infection by Heligmosomoides polygyrus, a co-evolved pathosymbiont of mice, to assess the epithelial response to disruption of the mucosal barrier. H. polygyrus disrupts tissue integrity by penetrating the duodenal mucosa, where it develops while surrounded by a multicellular granulomatous infiltrate2. Crypts overlying larvae-associated granulomas did not express intestinal stem cell markers, including Lgr53, in spite of continued epithelial proliferation. Granuloma-associated Lgr5- crypt epithelium activated an interferon-gamma (IFN-γ)-dependent transcriptional program, highlighted by Sca-1 expression, and IFN-γ-producing immune cells were found in granulomas. A similar epithelial response accompanied systemic activation of immune cells, intestinal irradiation, or ablation of Lgr5+ intestinal stem cells. When cultured in vitro, granuloma-associated crypt cells formed spheroids similar to those formed by fetal epithelium, and a sub-population of H. polygyrus-induced cells activated a fetal-like transcriptional program, demonstrating that adult intestinal tissues can repurpose aspects of fetal development. Therefore, re-initiation of the developmental program represents a fundamental mechanism by which the intestinal crypt can remodel itself to sustain function after injury
Global Ultrasound Elastography Using Convolutional Neural Network
Displacement estimation is very important in ultrasound elastography and
failing to estimate displacement correctly results in failure in generating
strain images. As conventional ultrasound elastography techniques suffer from
decorrelation noise, they are prone to fail in estimating displacement between
echo signals obtained during tissue distortions. This study proposes a novel
elastography technique which addresses the decorrelation in estimating
displacement field. We call our method GLUENet (GLobal Ultrasound Elastography
Network) which uses deep Convolutional Neural Network (CNN) to get a coarse
time-delay estimation between two ultrasound images. This displacement is later
used for formulating a nonlinear cost function which incorporates similarity of
RF data intensity and prior information of estimated displacement. By
optimizing this cost function, we calculate the finer displacement by
exploiting all the information of all the samples of RF data simultaneously.
The Contrast to Noise Ratio (CNR) and Signal to Noise Ratio (SNR) of the strain
images from our technique is very much close to that of strain images from
GLUE. While most elastography algorithms are sensitive to parameter tuning, our
robust algorithm is substantially less sensitive to parameter tuning.Comment: 4 pages, 4 figures; added acknowledgment section, submission type
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Magnetic-force-microscope study of interlayer "kinks" in individual vortices in underdoped cuprate YBaCuO superconductor
We use magnetic force microscopy to both image and manipulate individual
vortex lines threading single crystalline YBaCuO, a layered
superconductor. We find that when we pull the top of a pinned vortex, it may
not tilt smoothly. Sometimes, we observe a vortex to break into discrete
segments that can be described as short stacks of pancake vortices, similar to
the "kinked" structure proposed by Benkraouda and Clem. Quantitative analysis
gives an estimate of the pinning force and the coupling between the stacks. Our
measurements highlight the discrete nature of stacks of pancake vortices in
layered superconductors
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