[Allergic bronchopullmonary aspergillosis (ABPA) - an Update].

Allergic bronchopulmonary aspergillosis (ABPA) is a regular occurrence in everyday pneumology. ABPA should be considered in patients with severe asthma, in mould allergic patients with very high serum IgE levels and in patients with cystic fibrosis. The aim should be to make the diagnosis as early as possible in the course of the disease to avoid late complications such as bronchiectasis and fibrotic lung remodelling.

Exploring the Reactivity of Donor-Acceptor Systems through a Combined Conceptual and Constrained DFT Approach.

In the context of the conceptual density functional theory (cDFT) and based on the computational efficiency of the constrained DFT (CDFT), we demonstrate that chemical reactivity can be governed by the difference between the local interacting chemical potentials of the reactants (referred as ), in agreement with Sanderson's equalization principle. In a proof-of-concept study, we investigated illustrative examples involving typical non-covalent donor-acceptor systems and reactive systems are provided. For the selected systems, our approach reveals significant mimicking between and the DFT-computed intermolecular interaction energy profiles.

Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease.

Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill defined. Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small-airway inflammation, emphysema, and severe breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased in early-stage COPD, and changes in molecular and functional neutrophil states correlate with lung function decline.

The Topological Analysis of the ELF Localization Function: Quantitative Prediction of Hydrogen Bonds in the Guanine-Cytosine Pair.

In this contribution, we recall and test a new methodology designed to identify the favorable reaction pathway between two reactants. Applied to the formation of the DNA guanine (G) -cytosine (C) pair, we successfully predict the best orientation between the base pairs held together by hydrogen bonds and leading to the formation of the typical Watson Crick structure of the GC pair. Beyond the global minimum, some local stationary points of the targeted pair are also clearly identified.

New insights in chemical reactivity from quantum chemical topology.

Based on the quantum chemical topology of the modified electron localization function ELF , an efficient and robust mechanistic methodology designed to identify the favorable reaction pathway between two reactants is proposed. We first recall and reshape how the supermolecular interaction energy can be evaluated from only three distinct terms, namely the intermolecular coulomb energy, the intermolecular exchange-correlation energy and the intramolecular energies of reactants. Thereafter, we show that the reactivity between the reactants is driven by the first-order variation in the coulomb intermolecular energy defined in terms of the response to changes in the number of electrons.

Novel approach to accurately predict bond strength and ligand lability in platinum-based anticancer drugs.

Prompted by the antineoplastic properties of cisplatin, a plethora of platinum(ii)-based complexes have been synthesized in the past decades. At present, their rational design is based on a number of structure-activity relationships involving the nature of the ligands initially coordinated to platinum(ii): either non-labile (acting as a carrier) or labile (undergoing substitution). The coordinate bond strength of the labile ligand plays a key role in the first step of the drug mechanism of action, i.

New Way for Probing Bond Strength.

The covalent chemical bond is intimately linked to electron sharing between atoms. The recent independent gradient model (IGM) and its δ descriptor provide a way to quantify locally this electron density interpenetration from wavefunction calculations. Each bond has its own IGM-δ signature.

Combined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth.

Toll-like receptors (TLRs) are located either on the cell surface or intracellularly in endosomes and their activation normally contributes to the induction of protective immune responses. However, in cancer their activation by endogenous ligands can modulate tumour progression. It is currently unknown how endosomal TLRs regulate endogenous anti-tumour immunity.

Differential immunomodulatory activity of tumor cell death induced by cancer therapeutic toll-like receptor ligands.

Synthetic toll-like receptor (TLR) ligands stimulate defined immune cell subsets and are currently tested as novel immunotherapeutic agents against cancer with, however, varying clinical efficacy. Recent data showed the expression of TLR receptors also on tumor cells. In this study we investigated immunological events associated with the induction of tumor cell death by poly(I:C) and imiquimod.

Survival of residual neutrophils and accelerated myelopoiesis limit the efficacy of antibody-mediated depletion of Ly-6G+ cells in tumor-bearing mice.

Expansion of Ly-6G(+) myeloid cells has been reported in most murine cancer models. However, divergent findings exist regarding the role and effect of these cells on host immunity and tumor progression. Antibody-mediated depletion of Ly-6G(+) cells is a common technique to assess the in vivo relevance of these cells.

Toll-like receptor 9 promotes cardiac inflammation and heart failure during polymicrobial sepsis.

Background: Aim was to elucidate the role of toll-like receptor 9 (TLR9) in cardiac inflammation and septic heart failure in a murine model of polymicrobial sepsis.

Methods: Sepsis was induced via colon ascendens stent peritonitis (CASP) in C57BL/6 wild-type (WT) and TLR9-deficient (TLR9-D) mice. Bacterial load in the peritoneal cavity and cardiac expression of inflammatory mediators were determined at 6, 12, 18, 24, and 36 h.