Implanted porous precision templated scaffolds (PTS) with 40‐µm spherical pores reduce inflammation and foreign body reaction (FBR) while increasing vascular density upon implantation. Larger or smaller pores, however, promote chronic inflammation and FBR. While macrophage (MØ) recruitment and polarization participates in perpetuating this pore‐size‐mediated phenomenon, the driving mechanism of this unique pro‐healing response is poorly characterized. We hypothesized that the primarily myeloid PTS resident cells release small extracellular vesicles (sEVs) that induce pore‐size‐dependent pro‐healing effects in surrounding T cells. Upon profiling resident immune cells and their sEVs from explanted 40‐µm‐ (pro‐healing) and 100‐µm‐pore diameter (inflammatory) PTS, we found that PTS pore size did not affect PTS resident immune cell population ratios or the proportion of myeloid sEVs generated from explanted PTS. However, quantitative transcriptomic assessment indicated cell and sEV phenotype were pore size dependent. In vitro experiments demonstrated the ability of PTS cell‐derived sEVs to stimulate T cells transcriptionally and proliferatively. Specifically, sEVs isolated from cells inhabiting explanted 100 μm PTS significantly upregulated Th1 inflammatory gene expression in immortalized T cells. sEVs isolated from cell inhabiting both 40‐ and 100‐μm PTS upregulated essential Treg transcriptional markers in both primary and immortalized T cells. Finally, we investigated the effects of Treg depletion on explanted PTS resident cells. FoxP3+ cell depletion suggests Tregs play a unique role in balancing T cell subset ratios, thus driving host response in 40‐μm PTS. These results indicate that predominantly 40‐µm PTS myeloid cell‐derived sEVs affect T cells through a distinct, pore‐size‐mediated modality.
Uropathogenic Escherichia coli account for the largest proportion of nosocomial infections in the United States. Nosocomial infections are a major source of increased costs and treatment complications. Many infections are biofilm associated, rendering antibiotic treatments ineffective or cause additional complications (e.g., microbiome depletion). This work presents a potentially complementary non-antibiotic strategy to fight nosocomial infections by inhibiting the formation of amyloid fibrils, a proteinaceous structural reinforcement known as curli in E. coli biofilms. Despite extensive characterization of the fibrils themselves and their associated secretion system, mechanistic details of curli assembly in vivo remain unclear. We hypothesized that, like other amyloid fibrils, curli polymerization involves a unique secondary structure termed “α-sheet”. Biophysical studies herein confirmed the presence of α-sheet structure in prefibrillar species of CsgA, the major component of curli, as it aggregated. Binding of synthetic α-sheet peptides to the soluble α-sheet prefibrillar species inhibited CsgA aggregation in vitro and suppressed amyloid fibril formation in biofilms. Application of synthetic α-sheet peptides also enhanced antibiotic susceptibility and dispersed biofilm-resident bacteria for improved uptake by phagocytic cells. The ability of synthetic α-sheet peptides to reduce biofilm formation, improve antibiotic susceptibility, and enhance clearance by macrophages has broad implications for combating biofilm-associated infections.
Urban pressures on farm real estate taxes have led, in the last decade, to adoption of differential assessment of farmland in at least 16 states. Broadly speaking, the laws fall into three categories: Preferential assessment, deferred taxation, and restrictive agreements. The laws are analyzed both from the standpoint of tax policy and from the standpoint of development policy. In neither case is it possible, given the present state of knowledge, to conclude firmly that the laws are desirable or undesirable. The analysis does, however, suggest a number of potential problems which should be analyzed before decisions are made.
If we could get a nickel for every time the demise of the property tax has been predicted in this century, we probably could invest the proceeds and use the interest to finance a program of property tax reform. In a sense, this subject is old.In another sense, however, there is something very new about discussing alternative ways of raising money for local governments. In August 1971, the California Supreme Court issued its decision in the now well-known case of Serrano v. Priest; in March 1973, the U.S. Supreme Court overturned a similar ruling by a lower court in Texas. The Court ruled that the present system of financing local schools in California, which relies heavily on the property tax, unconstitutionally “conditions the full entitlement to such interest on wealth, classifies its recipients on the basis of their collective affluence and makes the quality of a child's education depend upon the resources of his school district and ultimately upon the pocketbook of his parents.” Since that time, more than 50 similar suits have been filed in some 31 states, and the U.S. Supreme Court is reviewing an appeal from Texas in a case similar to Serrano.
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