Stereoisomeric semiconducting radical cation salts of chiral bis(2-hydroxypropylthio)ethylenedithioTTF with tetrafluoroborate anions

The new chiral TTF-based donor molecule bis(2-hydroxypropylthio)ethylenedithiotetrathiafulvalene has produced enantiopure R,R and S,S radical cation salts with the tetrafluoroborate anion as well as the nearly isostructural meso/racemate mixture. The enantiopure R,R or S,S salts are both 1:1 semiconducting salts with activation energies of 0.19–0.24 eV, both crystallising in the orthorhombic space group C2221. The semiconducting salt containing both meso and racemic donor cations has a very similar crystal structure but crystallising in the monoclinic space group C2/c (β = 91.39°) with similar S⋯S interactions but a smaller activation energy of 0.15–0.17 eV. This is in contrast to previous families of this type where the disordered racemate has a larger activation energy than its enantiopure salts

Gauge symmetry, chirality and parity violation in four-particle systems: Coulomb's law as a universal molecular function

Following recent work in search of a universal function (Van Hooydonk, Eur J Inorg Chem, 1999, 1617), we test symmetric potentials for reproducing molecular potential energy curves (PECs). For a bond, a four-particle system, charge inversion is the key to explain this shape generically. A parity adapted Hamiltonian reduces from ten to two terms. The analytical perturbed Coulomb function scales attractive and repulsive branches of 13 PECs (HH, HF, LiH, KH, AuH, LiLi, LiF, KLi, NaCs, RbRb,RbCs, CsCs and II) in a single straight line. Turning points are reproduced with a deviation of 0.3 % (0.007 angstrom). At the repulsive side, the deviation is 0.2 % (0.003 angstrom). The ab initio zero molecular parameter function gives PECs of acceptable quality, just using atomic ionisation energies. The function can be used as a model potential for inverting energy levels. The theory may be tested with femtochemistry. Reactions between hydrogen and anti-hydrogen, feasible in the near future, will probably produce normal HH.Comment: 90 p., 5 tables, 35 figure

Effect of VX-770 in Persons with Cystic Fibrosis and the G551D- CFTR Mutation

A new approach in the treatment of cystic fibrosis involves improving the function of mutant cystic fibrosis transmembrane conductance regulator (CFTR). VX-770, a CFTR potentiator, has been shown to increase the activity of wild-type and defective cell-surface CFTR in vitro

Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease

<div><p>Chronic lung infections in cystic fibrosis (CF) patients are composed of complex microbial communities that incite persistent inflammation and airway damage. Despite the high density of bacteria that colonize the lower airways, nutrient sources that sustain bacterial growth <i>in vivo</i>, and how those nutrients are derived, are not well characterized. In this study, we examined the possibility that mucins serve as an important carbon reservoir for the CF lung microbiota. While <i>Pseudomonas aeruginosa</i> was unable to efficiently utilize mucins in isolation, we found that anaerobic, mucin-fermenting bacteria could stimulate the robust growth of CF pathogens when provided intact mucins as a sole carbon source. 16S rRNA sequencing and enrichment culturing of sputum also identified that mucin-degrading anaerobes are ubiquitous in the airways of CF patients. The collective fermentative metabolism of these mucin-degrading communities <i>in vitro</i> generated amino acids and short chain fatty acids (propionate and acetate) during growth on mucin, and the same metabolites were also found in abundance within expectorated sputum. The significance of these findings was supported by <i>in vivo P</i>. <i>aeruginosa</i> gene expression, which revealed a heightened expression of genes required for the catabolism of propionate. Given that propionate is exclusively derived from bacterial fermentation, these data provide evidence for an important role of mucin fermenting bacteria in the carbon flux of the lower airways. More specifically, microorganisms typically defined as commensals may contribute to airway disease by degrading mucins, in turn providing nutrients for pathogens otherwise unable to efficiently obtain carbon in the lung.</p></div

Mucin-enrichment metabolite profiling.

<p>(A) short chain fatty acids (n = 8) and (B) amino acids (n = 10) were quantified in mucin enrichment cultures. Arginine and cysteine were unable to be quantified due to their co-elution with other metabolites.</p

<i>acsA</i> and <i>prpB</i> mutants are defective in mucin cross-feeding.

<p>PA14 mutants lacking genes required for acetate and propionate catabolism show a significant defect in co-culture with mucin-fermenting anaerobes. Asterisks indicate significance relative to PA14.</p

Short chain fatty acids are abundant in the CF airways.

<p>(A) Direct measurements of (A) acetate and (B) propionate in paired sputum and saliva samples from CF patients. Acetate concentrations were significantly higher in sputum (**, <i>p =</i> 0.004).</p

Model for the role of mucin fermenting bacteria in the progression of CF lung disease.

<p>(A) In healthy airways or CF newborns, airway surface liquid harbors a low number of aspirated oral bacteria. (B) In CF patients, impaired mucociliary clearance and defective immune responses increase the residence time of oral-associated anaerobes. In turn, their ability to degrade and ferment respiratory mucins modifies the airway environment for secondary colonizers. (C) The abundance of fermentation byproducts within sputum facilitates pathogen colonization, heightened inflammation, neutrophil recruitment and sputum accumulation. (D) In late stages of disease, host inflammatory responses and epithelial damage shape the bioavailable nutrient pool, increasing the abundance of pathogens while oral anaerobes are eliminated by the host and via broad spectrum antibiotic therapies.</p