136 research outputs found
A Coarse-Grained Biophysical Model of E. coli and Its Application to Perturbation of the rRNA Operon Copy Number
We propose a biophysical model of Escherichia coli that predicts growth rate
and an effective cellular composition from an effective, coarse-grained
representation of its genome. We assume that E. coli is in a state of balanced
exponential steadystate growth, growing in a temporally and spatially constant
environment, rich in resources. We apply this model to a series of past
measurements, where the growth rate and rRNA-to-protein ratio have been
measured for seven E. coli strains with an rRNA operon copy number ranging from
one to seven (the wild-type copy number). These experiments show that growth
rate markedly decreases for strains with fewer than six copies. Using the
model, we were able to reproduce these measurements. We show that the model
that best fits these data suggests that the volume fraction of macromolecules
inside E. coli is not fixed when the rRNA operon copy number is varied.
Moreover, the model predicts that increasing the copy number beyond seven
results in a cytoplasm densely packed with ribosomes and proteins. Assuming
that under such overcrowded conditions prolonged diffusion times tend to weaken
binding affinities, the model predicts that growth rate will not increase
substantially beyond the wild-type growth rate, as indicated by other
experiments. Our model therefore suggests that changing the rRNA operon copy
number of wild-type E. coli cells growing in a constant rich environment does
not substantially increase their growth rate. Other observations regarding
strains with an altered rRNA operon copy number, such as nucleoid compaction
and the rRNA operon feedback response, appear to be qualitatively consistent
with this model. In addition, we discuss possible design principles suggested
by the model and propose further experiments to test its validity
Signal One and Two Blockade Are Both Critical for Non-Myeloablative Murine HSCT across a Major Histocompatibility Complex Barrier
Non-myeloablative allogeneic haematopoietic stem cell transplantation (HSCT) is rarely achievable clinically, except where donor cells have selective advantages. Murine non-myeloablative conditioning regimens have limited clinical success, partly through use of clinically unachievable cell doses or strain combinations permitting allograft acceptance using immunosuppression alone. We found that reducing busulfan conditioning in murine syngeneic HSCT, increases bone marrow (BM):blood SDF-1 ratio and total donor cells homing to BM, but reduces the proportion of donor cells engrafting. Despite this, syngeneic engraftment is achievable with non-myeloablative busulfan (25 mg/kg) and higher cell doses induce increased chimerism. Therefore we investigated regimens promoting initial donor cell engraftment in the major histocompatibility complex barrier mismatched CBA to C57BL/6 allo-transplant model. This requires full myeloablation and immunosuppression with non-depleting anti-CD4/CD8 blocking antibodies to achieve engraftment of low cell doses, and rejects with reduced intensity conditioning (≤75 mg/kg busulfan). We compared increased antibody treatment, G-CSF, niche disruption and high cell dose, using reduced intensity busulfan and CD4/8 blockade in this model. Most treatments increased initial donor engraftment, but only addition of co-stimulatory blockade permitted long-term engraftment with reduced intensity or non-myeloablative conditioning, suggesting that signal 1 and 2 T-cell blockade is more important than early BM niche engraftment for transplant success
Validation of reflectance pulse oximetry : An evaluation of a new sensor in piglets
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CCDC 261613: Experimental Crystal Structure Determination
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures
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