Investigating the effect of antibiotics on quorum sensing with whole-cell biosensing systems

Quorum sensing (QS) allows bacteria to communicate with one another by means of QS signaling molecules and control certain behaviors in a group-based manner, including pathogenicity and biofilm formation. Bacterial gut microflora may play a role in inflammatory bowel disease pathogenesis, and antibiotics are one of the available therapeutic options for Crohn’s disease. In the present study, we employed genetically engineered bioluminescent bacterial whole-cell sensing systems as a tool to evaluate the ability of antibiotics commonly employed in the treatment of chronic inflammatory conditions to interfere with QS. We investigated the effect of ciprofloxacin, metronidazole, and tinidazole on quorum sensing. Several concentrations of individual antibiotics were allowed to interact with two different types of bacterial sensing cells, in both the presence and absence of a fixed concentration of N-acylhomoserine lactone (AHL) QS molecules. The antibiotic effect was then determined by monitoring the biosensor’s bioluminescence response. Ciprofloxacin, metronidazole, and tinidazole exhibited a dose-dependent augmentation in the response of both bacterial sensing systems, thus showing an AHL-like effect. Additionally, such an augmentation was observed, in both the presence and absence of AHL. The data obtained indicate that ciprofloxacin, metronidazole, and tinidazole may interfere with bacterial communication systems. The results suggest that these antibiotics, at the concentrations tested, may themselves act as bacterial signaling molecules. The beneficial effect of these antibiotics in the treatment of intestinal inflammation may be due, at least in part, to their effect on QS-related bacterial behavior in the gut.     

Comparison of uranyl extraction mechanisms in an ionic liquid by use of malonamide or malonamide-functionalized ionic liquid

The extraction of uranyl from acidic (HNO(3)) aqueous solutions toward an ionic liquid phase, C(1)-C(4)-imTf(2)N (1-methyl,3-butylimidazolium Tf(2)N), has been investigated as a function of initial acid concentration and ligand concentration for two different extracting moieties: a classical malonamide, N,N'-dimethyl-N,N'-dibutylmalonamide (DMDBMA) and a functionalized IL composed of the Tf(2)N(-) anion and an imidazolium cation on which a malonamide pattern has been grafted (FIL-MA). The extraction mechanism, as demonstrated through the influence of added C(1)-C(4)-imCl or added LiTf(2)N in the aqueous phase, is slightly different between the DMDBMA and FIL-MA extracting agents. Modeling of the extraction data evidences a double extraction mechanism, with cation exchange of UO(2)(2+)versus 2 H(+) for DMDBMA or versus C(1)-C(4) -im(+) and H(+) for FIL-MA at low acidic values, and through anion exchange of [UO(2)(NO(3))(3)](-)versus Tf(2)N(-) for both ligands at high HNO(3) concentrations. The FIL-MA molecule is more efficient than its classical DMDBMA parent.     

Structural Synthon Approach to the Study of Stacking Faults in the Layered Double Hydroxides of Lithium and Aluminum

A single layer of the Li‐Al layered double hydroxide (LDH) can be considered to be a structural synthon that can be stacked in a number of ways to give rise to the polytypes of the Li‐Al LDH family. The topotactic imbibition of lithium into gibbsite and bayerite precursors gives rise to crystalline 2H and 1M₁ polytypes respectively. In contrast the sample formed through a gel to crystallite route is found to be a 1M₁ polytype with stacking disorders whose local symmetry corresponds to the 1M₂ polytype. On heating, a solid‐solid 1M₁→1H polytype transformation is observed.     

A scale value for the balance inside a historical opera house

In the framework of opera house acoustics, the term "balance" refers to the acoustical competition between the singer on the stage and the orchestra in the pit. The mechanism allowing the operatic singers to be heard over the orchestra has to do with their skill in enhancing the vocal emission by a peculiar use of the formant frequencies. This vital factor is sensed by the listeners and, apart from the obvious sound power ratio of the stage and the pit sources, is the main cue that helps to formulate a subjective impression of the balance. To achieve its objective qualification, two calibrated sound sources can be placed on the stage and in the pit, respectively, and their sound level difference is measured at the listeners' seats. The scope of this work is to investigate the relationship between the subjective impression and the objective indicator of the balance and to develop a scale value for the parameter in the case of a historical opera house. For this scope a set of acoustical data from the Teatro Comunale in Ferrara will be used to create synthetic sound fields with controlled conditions of the balance between the stage and the pit. This methodology employs an anechoic piece for soprano (with piano accompaniment) and is implemented in a dead room equipped with an acoustical rendering system. The sound fields are used to investigate the appropriate balance values by means of listening tests. The results of the scaling exercise show that a suitable range of values can be extracted and that the sound from the stage and the pit is perceived as balanced when the loudness difference between the two is comprised within -2.0 dBA and +2.3 dBA.     

A Molecular Tool Targeting the Base-Flipping Activity of Human UHRF1

During DNA replication, ubiquitin-like, containing PHD and RING fingers domains 1 (UHRF1) plays key roles in the inheritance of methylation patterns to daughter strands by recognizing through its SET and RING-associated domain (SRA) the methylated CpGs and recruiting DNA methyltransferase 1 (DNMT1). Herein, our goal is to identify UHRF1 inhibitors targeting the 5′-methylcytosine (5mC) binding pocket of the SRA domain to prevent the recognition and flipping of 5mC and determine the molecular and cellular consequences of this inhibition. For this, we used a multidisciplinary strategy combining virtual screening and molecular modeling with biophysical assays in solution and cells. We identified an anthraquinone compound able to bind to the 5mC binding pocket and inhibit the base-flipping process in the low micromolar range. We also showed in cells that this hit impaired the UHRF1/DNMT1 interaction and decreased the overall methylation of DNA, highlighting the critical role of base flipping for DNMT1 recruitment and providing the first proof of concept of the druggability of the 5mC binding pocket. The selected anthraquinone appears thus as a key tool to investigate the role of UHRF1 in the inheritance of methylation patterns, as well as a starting point for hit-to-lead optimizations.     

Approximating eigenfunctions of Fredholm operators in Banach spaces

A singular Fredholm operator A is perturbed by an operator of finite rank to obtain an invertible operator B. Theory previously developed for A and B in Hilbert spaces is extended here to Banach spaces. The operator B^?1 is used to construct independent elements in the null spaces N(A), N(A²),…, N(A^k), for some positive integer k, and a basis for N(A) and N(A²). The theory is used to compute approximations to eigenfunctions and generalized eigenfunctions of integral operators.     

Stability and extensibility results for abstract skew-product semiflows

In this paper we present new stability and extensibility results for skew-product semiflows with a minimal base flow. In particular, we describe the structure of uniformly stable and uniformly asymptotically stable sets admitting backwards orbits and the structure of omega-limit sets. As an application, the occurrence of almost periodic and almost automorphic dynamics for monotone non-autonomous infinite delay functional differential equations is analyzed.