159 research outputs found
Loss of DAP12 and FcRγ drives exaggerated IL-12 production and CD8(+) T cell response by CCR2(+) Mo-DCs
Dap12 and FcRγ, the two transmembrane ITAM-containing signaling adaptors expressed in dendritic cells (DC), are implicated in the regulation of DC function. Several activating and adhesion receptors including integrins require these chains for their function in triggering downstream signaling and effector pathways, however the exact role(s) for Dap12 and FcRγ remains elusive as their loss can lead to both attenuating and enhancing effects. Here, we report that mice congenitally lacking both Dap12 and FcRγ chains (DF) show a massively enhanced effector CD8(+) T cell response to protein antigen immunization or West Nile Virus (WNV) infection. Thus, immunization of DF mice with MHCI-restricted OVA peptide leads to accumulation of IL-12-producing monocyte-derived dendritic cells (Mo-DC) in draining lymph nodes, followed by vastly enhanced generation of antigen-specific IFNγ-producing CD8(+) T cells. Moreover, DF mice show increased viral clearance in the WNV infection model. Depletion of CCR2+ monocytes/macrophages in vivo by administration anti-CCR2 antibodies or clodronate liposomes completely prevents the exaggerated CD8+ T cell response in DF mice. Mechanistically, we show that the loss of Dap12 and FcRγ-mediated signals in Mo-DC leads to a disruption of GM-CSF receptor-induced STAT5 activation resulting in upregulation of expression of IRF8, a transcription factor. Consequently, Dap12- and FcRγ-deficiency exacerbates GM-CSF-driven monocyte differentiation and production of inflammatory Mo-DC. Our data suggest a novel cross-talk between DC-ITAM and GM-CSF signaling pathways, which controls Mo-DC differentiation, IL-12 production, and CD8(+) T cell responses
A Study of the \eta \pi^{0} Spectrum and Search for a J^{PC} = 1^{-+} Exotic Meson
A partial wave analysis (PWA) of the of the system (where ) produced in the charge exchange reaction at an incident momentum of 18 GeV is presented as a function of
invariant mass, , and momentum transfer squared,
, from the incident to the outgoing system. , and waves were included in the PWA. The
and states are clearly observed in the overall
effective mass distribution as well as in the amplitudes associated with
wave and waves respectively after partial wave decomposition. The observed
distributions in moments (averages of spherical harmonics) were compared to the
results from the PWA and the two are consistent. The distribution in
for individual waves associated with natural and
unnatural parity exchange in the -channel are consistent with Regge
phenomenology. Of particular interest in this study is the wave since this
leads to an exotic for the system. A wave is
present in the data, however attempts to describe the mass dependence of the
amplitude and phase motion with respect to the wave as a Breit-Wigner
resonance are problematic. This has implications regarding the existence of a
reported exotic meson decaying into with a mass
near 1.4 GeV.Comment: 19 pages, 29 figures, to appear in Phys. Rev.
Observation of the Dynamic Beta Effect at CESR with CLEO
Using the silicon strip detector of the CLEO experiment operating at the
Cornell Electron-positron Storage Ring (CESR), we have observed that the
horizontal size of the luminous region decreases in the presence of the
beam-beam interaction from what is expected without the beam-beam interaction.
The dependence on the bunch current agrees with the prediction of the dynamic
beta effect. This is the first direct observation of the effect.Comment: 9 page uuencoded postscript file, postscritp file also available
through http://w4.lns.cornell.edu/public/CLNS, submitted to Phys. Rev.
Macaques can contribute to greener practices in oil palm plantations when used as biological pest control.
Conversion of tropical forests into oil palm plantations reduces the habitats of many species, including primates, and frequently leads to human-wildlife conflicts. Contrary to the widespread belief that macaques foraging in the forest-oil palm matrix are detrimental crop pests, we show that the impact of macaques on oil palm yield is minor. More importantly, our data suggest that wild macaques have the potential to act as biological pest control by feeding on plantation rats, the major pest for oil palm crops, with each macaque group estimated to reduce rat populations by about 3,000 individuals per year (mitigating annual losses of 112 USD per hectare). If used for rodent control in place of the conventional method of poison, macaques could provide an important ecosystem service and enhance palm oil sustainability
MDCK Cystogenesis Driven by Cell Stabilization within Computational Analogues
The study of epithelial morphogenesis is fundamental to increasing our
understanding of organ function and disease. Great progress has been made
through study of culture systems such as Madin-Darby canine kidney (MDCK) cells,
but many aspects of even simple morphogenesis remain unclear. For example, are
specific cell actions tightly coupled to the characteristics of the cell's
environment or are they more often cell state dependent? How does the single
lumen, single cell layer cyst consistently emerge from a variety of cell
actions? To improve insight, we instantiated in silico analogues that used
hypothesized cell behavior mechanisms to mimic MDCK cystogenesis. We tested them
through in vitro experimentation and quantitative validation. We observed novel
growth patterns, including a cell behavior shift that began around day five of
growth. We created agent-oriented analogues that used the cellular Potts model
along with an Iterative Refinement protocol. Following several refinements, we
achieved a degree of validation for two separate mechanisms. Both survived
falsification and achieved prespecified measures of similarity to cell culture
properties. In silico components and mechanisms mapped to in vitro counterparts.
In silico, the axis of cell division significantly affects lumen number without
changing cell number or cyst size. Reducing the amount of in silico luminal cell
death had limited effect on cystogenesis. Simulations provide an observable
theory for cystogenesis based on hypothesized, cell-level operating
principles
Induction of Ig light chain gene rearrangement in heavy chain-deficient B cells by activated Ras
Computer Simulation of Cellular Patterning Within the Drosophila Pupal Eye
We present a computer simulation and associated experimental validation of assembly of glial-like support cells into the interweaving hexagonal lattice that spans the Drosophila pupal eye. This process of cell movements organizes the ommatidial array into a functional pattern. Unlike earlier simulations that focused on the arrangements of cells within individual ommatidia, here we examine the local movements that lead to large-scale organization of the emerging eye field. Simulations based on our experimental observations of cell adhesion, cell death, and cell movement successfully patterned a tracing of an emerging wild-type pupal eye. Surprisingly, altering cell adhesion had only a mild effect on patterning, contradicting our previous hypothesis that the patterning was primarily the result of preferential adhesion between IRM-class surface proteins. Instead, our simulations highlighted the importance of programmed cell death (PCD) as well as a previously unappreciated variable: the expansion of cells' apical surface areas, which promoted rearrangement of neighboring cells. We tested this prediction experimentally by preventing expansion in the apical area of individual cells: patterning was disrupted in a manner predicted by our simulations. Our work demonstrates the value of combining computer simulation with in vivo experiments to uncover novel mechanisms that are perpetuated throughout the eye field. It also demonstrates the utility of the Glazier–Graner–Hogeweg model (GGH) for modeling the links between local cellular interactions and emergent properties of developing epithelia as well as predicting unanticipated results in vivo
3D Multi-Cell Simulation of Tumor Growth and Angiogenesis
We present a 3D multi-cell simulation of a generic simplification of vascular tumor growth which can be easily extended and adapted to describe more specific vascular tumor types and host tissues. Initially, tumor cells proliferate as they take up the oxygen which the pre-existing vasculature supplies. The tumor grows exponentially. When the oxygen level drops below a threshold, the tumor cells become hypoxic and start secreting pro-angiogenic factors. At this stage, the tumor reaches a maximum diameter characteristic of an avascular tumor spheroid. The endothelial cells in the pre-existing vasculature respond to the pro-angiogenic factors both by chemotaxing towards higher concentrations of pro-angiogenic factors and by forming new blood vessels via angiogenesis. The tumor-induced vasculature increases the growth rate of the resulting vascularized solid tumor compared to an avascular tumor, allowing the tumor to grow beyond the spheroid in these linear-growth phases. First, in the linear-spherical phase of growth, the tumor remains spherical while its volume increases. Second, in the linear-cylindrical phase of growth the tumor elongates into a cylinder. Finally, in the linear-sheet phase of growth, tumor growth accelerates as the tumor changes from cylindrical to paddle-shaped. Substantial periods during which the tumor grows slowly or not at all separate the exponential from the linear-spherical and the linear-spherical from the linear-cylindrical growth phases. In contrast to other simulations in which avascular tumors remain spherical, our simulated avascular tumors form cylinders following the blood vessels, leading to a different distribution of hypoxic cells within the tumor. Our simulations cover time periods which are long enough to produce a range of biologically reasonable complex morphologies, allowing us to study how tumor-induced angiogenesis affects the growth rate, size and morphology of simulated tumors
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