Selective permeability of a biofilm matrix to some drugs has resulted in the development of drug tolerant bacteria. Here we studied the efficacy of a weak organic acid drug, N-acetyl-L-cysteine (NAC), on the eradication of biofilms formed by the mucoid strain of Pseudomonas aeruginosa and investigated the commonality of this drug with that of acetic acid. We showed that NAC and acetic acid at pH < pKa can penetrate the matrix and eventually kill 100% of the bacteria embedded in the biofilm. Once the bacteria are killed, the microcolonies swell in size and passively shed bacteria, suggesting that the bacteria act as crosslinkers within the extracellular matrix. Despite shedding of the bacteria, the remnant matrix remains intact and behaves as a pH-responsive hydrogel. These studies not only have implications for drug design but also offer a route to generate robust soft matter materials.
We compared the evolution of insulin resistance, hyperglycemia, and pancreatic β-cell dysfunction in the Nile rat (Arvicanthis niloticus), a diurnal rodent model of spontaneous type 2 diabetes (T2D), when maintained on regular laboratory chow versus a high-fiber diet. Chow-fed Nile rats already displayed symptoms characteristic of insulin resistance at 2 months (increased fat/lean mass ratio and hyperinsulinemia). Hyperglycemia was first detected at 6 months, with increased incidence at 12 months. By this age, pancreatic islet structure was disrupted (increased α-cell area), insulin secretion was impaired (reduced insulin secretion and content) in isolated islets, insulin processing was compromised (accumulation of proinsulin and C-peptide inside islets), and endoplasmic reticulum (ER) chaperone protein ERp44 was upregulated in insulin-producing β-cells. By contrast, high-fiber-fed Nile rats had normoglycemia with compensatory increase in β-cell mass resulting in maintained pancreatic function. Fasting glucose levels were predicted by the α/β-cell ratios. Our results show that Nile rats fed chow recapitulate the five stages of progression of T2D as occurs in human disease, including insulinresistant hyperglycemia and pancreatic islet β-cell dysfunction associated with ER stress. Modification of diet alone permits long-term β-cell compensation and prevents T2D.
343-356229:3 β-cell phenotype in type 2 diabetic Nile rats k yang and others
Frictional drag force on an object in Stokes flow follows a linear relationship with the velocity of translation and a translational drag coefficient. This drag coefficient is related to the size, shape, and orientation of the object. For rod-like objects, analytical solutions of the drag coefficients have been proposed based on three rough approximations of the rod geometry, namely the bead model, ellipsoid model, and cylinder model. These theories all agree that translational drag coefficients of rod-like objects are functions of the rod length and aspect ratio, but differ among one another on the correction factor terms in the equations. By tracking the displacement of the particles through stationary fluids of calibrated viscosity in magnetic tweezers setup, we experimentally measured the drag coefficients of micron-sized beads and their bead-chain formations with chain length of 2 to 27. We verified our methodology with analytical solutions of dimers of two touching beads, and compared our measured drag coefficient values of rod-like objects with theoretical calculations. Our comparison reveals several analytical solutions that used more appropriate approximation and derived formulae that agree with our measurement better.
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