Spatial models of pattern formation during phagocytosis.

Phagocytosis, the biological process in which cells ingest large particles such as bacteria, is a key component of the innate immune response. Fcγ receptor (FcγR)-mediated phagocytosis is initiated when these receptors are activated after binding immunoglobulin G (IgG). Receptor activation initiates a signaling cascade that leads to the formation of the phagocytic cup and culminates with ingestion of the foreign particle. In the experimental system termed "frustrated phagocytosis", cells attempt to internalize micropatterned disks of IgG. Cells that engage in frustrated phagocytosis form "rosettes" of actin-enriched structures called podosomes around the IgG disk. The mechanism that generates the rosette pattern is unknown. We present data that supports the involvement of Cdc42, a member of the Rho family of GTPases, in pattern formation. Cdc42 acts downstream of receptor activation, upstream of actin polymerization, and is known to play a role in polarity establishment. Reaction-diffusion models for GTPase spatiotemporal dynamics exist. We demonstrate how the addition of negative feedback and minor changes to these models can generate the experimentally observed rosette pattern of podosomes. We show that this pattern formation can occur through two general mechanisms. In the first mechanism, an intermediate species forms a ring of high activity around the IgG disk, which then promotes rosette organization. The second mechanism does not require initial ring formation but relies on spatial gradients of intermediate chemical species that are selectively activated over the IgG patch. Finally, we analyze the models to suggest experiments to test their validity.

Early results from implementation of a 'watch and wait' protocol for complete clinical response following chemoradiotherapy for rectal cancer.

BACKGROUND: Neoadjuvant long course chemoradiotherapy (NLCRT) for rectal cancer can result in complete pathological response (pCR). In 2017, we started offering patients who had a complete clinical response (cCR), a choice between total mesorectal excision (TME) and an intensive surveillance or 'watch and wait' (W&W) program. We report the early outcomes of this prospective study. METHODS: All patients undergoing NLCRT from 2017 to 2019 were included. All patients were restaged at 8 weeks, and those who had a cCR were offered TME or W&W. RESULTS: Of 59 patients who underwent NLCRT, 55 had restaging. Eleven of these patients had a cCR (20%). Three chose to have TME and all had a pCR. Eight were enrolled in W&W. Two patients were diagnosed with local regrowth and underwent TME at 7 and 17 months after NLCRT. A further nine patients, who were surgically unfit or refused TME, and had an excellent response to NLCRT, but one that did not reach criteria for a cCR, were also managed with W&W. Of these, two patients developed regrowth with distant metastases. From 2017 to 2019, of the 17 patients who were managed with a W&W approach, 13 patients have remained regrowth free after a median of 28 (13-58) months of W&W. CONCLUSION: Preliminary findings suggest management with W&W, following cCR, may be a safe alternative to TME. There have so far been no instances of distant failure, and those with cCR that had regrowth, were identified early and successfully managed with salvage TME.

Rates of Reaction of Atomic Oxygen III. Spiropentane, Cyclopentane, Cyclohexane, and Cycloheptane.

Rate constants have been measured from 307 to 652 K for the reactions of atomic oxygen (O3P) with spiropentane, cyclopentane, cyclohexane, and cycloheptane. The derived Arrhenius parameters are k(sp - C5H8) = 1013.60±0.10 exp[(-2890 ± 100)/T], k(cy - C5H10) = 1014.10±0.09 exp[(-2210 ± 100)/T], k(cy - C6H12) = 1014.35±0.09 exp[(-2350 ± 100)/T], and (cy - C7H14) = 1014.46±0.13 exp[(-2230 ± 100)/T] all in units of cm3 mol-1 s-1.