Eutypa dieback of grapevine is an important disease caused by the generalist Ascomycete fungus Eutypa lata. Despite the relevance of this species to the global wine industry, its genomic diversity ...remains unknown, with only a single publicly available genome assembly. Whole-genome sequencing and comparative genomics was performed on forty Australian E. lata isolates to understand the genome evolution, adaptation, population size and structure of these isolates. Phylogenetic and linkage disequilibrium decay analyses provided evidence of extensive gene flow through sexual recombination between isolates obtained from different geographic locations and hosts. Investigation of the genetic diversity of these isolates suggested rapid population expansion, likely as a consequence of the recent growth of the Australian wine industry. Genomic regions affected by selective sweeps were shown to be enriched for genes associated with secondary metabolite clusters and included genes encoding proteins with a role in nutrient acquisition, degradation of host cell wall and metal and drug resistance, suggesting recent adaptation to both abiotic factors and potentially host genotypes. Genome synteny analysis using long-read genome assemblies showed significant intraspecific genomic plasticity with extensive chromosomal rearrangements impacting the secondary metabolite production potential of this species. Finally, k-mer based GWAS analysis identified a potential locus associated with mycelia recovery in canes of Vitis vinifera that will require further investigations.
Pharmaceutical aerosols play a key role in the treatment of lung disorders, but also systemic diseases, due to their ability to target specific areas of the respiratory system (RS). This article ...focuses on identifying and clarifying the influence of various factors involved in the generation of aerosol micro- and nanoparticles on their regional distribution and deposition in the RS. Attention is given to the importance of process parameters during the aerosolization of liquids or powders and the role of aerosol flow dynamics in the RS. The interaction of deposited particles with the fluid environment of the lung is also pointed out as an important step in the mass transfer of the drug to the RS surface. The analysis presented highlights the technical aspects of preparing the precursors to ensure that the properties of the aerosol are suitable for a given therapeutic target. Through an analysis of existing technical limitations, selected strategies aimed at enhancing the effectiveness of targeted aerosol delivery to the RS have been identified and presented. These strategies also include the use of smart inhaling devices and systems with built-in AI algorithms.
The knowledge of possible acute and long-term health effects of aerosols inhaled from electronic cigarettes (ECs) is still limited partially due to incomplete awareness of physical phenomena related ...to EC-aerosol dynamics. This short review discusses the basic processes of aerosol transformation (dynamics) upon inhalation, indicating also the need for the accurate determination of the size of droplets in the inhaled EC-mist. The significance of differences in the aerosol particle size distribution for the prediction of regional deposition of inhaled mist in the respiratory system is highlighted as a decisive factor in the interactions of inhaled EC-aerosols with the organism.
Health effects of inhaling aerosol produced by electronic cigarettes (ECs) are still uncertain. This work analyzes ECs as specific inhalation devices, which can be characterized by aerodynamic ...resistance, size distribution of released droplets, and predicted regional and total lung deposition as a function of inhalation maneuver.
The internal resistance of two types of EC and a conventional cigarette was evaluated by measuring ΔP-Q curves. Particle size distribution in EC-emitted mist was determined by laser diffraction. The measured data were used to calculate lung deposition based on two approaches: multipath particle dosimetry model (MPPD) and Finlay-Martin correlations. Computations were done for the set of ventilation parameters of an EC user, and also for a by-stander.
Tested ECs had higher aerodynamic resistance (1.6-1.9 mbar(0.5) min/L) than tobacco cigarette (0.56 mbar(0.5) min/L), and these values are much above the high-resistant DPIs. The average mass median diameter of droplets emitted from ECs was 410 nm, with the average GSD = 1.6. Predicted total lung deposition of the mainstream aerosol was 15%-45% depending on the breathing scheme. An expected increase of particle size in the exhaled aerosol led to predictions of 15%-30% deposition efficiency during passive vaping.
ECs are characterized by high inhalatory resistance, so they require stronger physical effort to transfer cloud of droplets to the lungs, as compared, for example, to DPIs. A significant amount of aerosol is then exhaled, forming an unintentional source of particles to which by-standers are exposed. From this perspective, ECs are not optimal personal aerosol delivery devices.
Inhalation of aerosolized pharmaceuticals is a non-invasive and convenient method of drug delivery typically used for local treatment of lung diseases. Large absorption area of the pulmonary region ...opens up the possibility of fast and effective transfer of inhaled medicines to the circulation in order to obtain systemic effects. This review is devoted to selected albeit essential challenges of targeting aerosolized drugs to the blood via the pulmonary part of the respiratory system. The special attention is given to some physicochemical aspects of drug formulation which are essential for overcoming the air-blood barrier present in the lungs. It is deemed that a careful analysis of multifarious physical and engineering problems, related to aerosol fate in the lungs, is indispensable for a better design of inhalation delivery systems for systemic drugs.
The grapevine trunk disease, Eutypa dieback (ED), causes significant vine decline and yield reduction. For many years, the fungus Eutypa lata was considered the main pathogen causing ED of grapevines ...in Australia. Recent studies showed other Diatrypaceous fungi were also associated with vines exhibiting dieback symptoms but there is limited information on how these fungal pathogens spread in vineyards. Thus, information on the spore dispersal patterns of Diatrypaceous fungi in different wine regions will assist in identifying high-risk infection periods in vineyards. Using more than 6800 DNA samples from airborne spores collected from eight wine regions in south-eastern Australia over 8 years using a Burkard spore trap, this study investigated the diversity and abundance of Diatrypaceous species, using multi-faceted molecular tools. A multi-target quantitative PCR (qPCR) assay successfully detected and quantified Diatrypaceous spores from 30% of the total samples with spore numbers and frequency of detection varying between regions and years. The high-resolution melting analysis (HRMA) coupled with DNA sequencing identified seven species, with E. lata being present in seven regions and the most prevalent species in the Adelaide Hills, Barossa Valley and McLaren Vale. Cryptovalsa ampelina and Diatrype stigma were the predominant species in the Clare Valley and Coonawarra, respectively while Eutypella citricola and Eu. microtheca dominated in the Hunter Valley and the Riverina regions. This study represents the first report of D. stigma and Cryptosphaeria multicontinentalis in Australian vineyards. This study further showed rainfall as a primary factor that triggers spore release, however, other weather factors that may influence the spore release in different climatic regions of Australia still requires further investigation.
Inhalation therapy is a convenient method of treating respiratory diseases. The key factors required for inhalation are the preparation of drug carriers (aerosol particles) allowing reproducible ...dosing during administration. These technical challenges are accomplished with a variety of inhalation devices (inhalers) and medicinal formulations, which are optimized to be easily converted into inhalable aerosols. Areas covered: This review is focused on the most important, but often overlooked, effects, which are required for the reliable and reproducible inhalable drug administration. The effects of patient-related issues that influence inhalation therapy, such as proper selection of inhalers for specific cases is discussed. We also discuss factors that are the most essential if generic inhalation product should be considered equivalent to the drugs with the clinically confirmed efficacy. Expert opinion: Proper device selection is crucial in clinical results of inhalation therapy. The patients' ability to coordinate inhalation with actuation, generation of optimal flow through the device, use of optimal inspiratory volume, all produces crucial effects on disease control. Also the severity of the disease process effects proper use of inhalers. Interchanging of inhalers can produce potentially conflicting problem regarding efficacy and safety of inhalation therapy.
This work investigates influence of different aluminosillicate nanoparticles (NPs) which are found in air in selected workplaces on the properties of the phospholipid (DPPC) monolayer at air–saline ...interface considered as ex vivo model of the lung surfactant (LS). The measurements were done under physiological-like conditions (deformable liquid interface at 37 °C) for NP concentrations matching the calculated lung doses after exposure in the working environment. Measured surface pressure–area (π–A) isotherms and compressibility curves demonstrated NP-induced changes in the structure and mechanical properties of the lipid monolayer. It was shown that hydrophilic nanomaterials (halloysite and bentonite) induced concentration-dependent impairment of DPPC’s ability of attaining high surface pressures on interfacial compression, suggesting a possibility of reduction of physiological function of natural LS. Hydrophobic montmorillonites affected DPPC monolayer in the opposite way; however, they significantly changed the mechanical properties of the air–liquid interface during compression. The results support the hypothesis of possible reduction or even degradation of the natural function of the lung surfactant induced by particle–phospholipid interactions after inhalation of nanoclays. Presented data do not only supplement the earlier results obtained with another LS model (animal-derived surfactant in oscillating bubble experiments) but also offer an explanation of physicochemical mechanisms responsible for detrimental effects which arise after deposition of inhaled nanomaterials on the surface of the respiratory system.
The effectiveness of inhalation therapy depends on aerosol size distribution, which determines the penetration and regional deposition of drug in the lungs. As the size of droplets inhaled from ...medical nebulizers varies depending on the physicochemical properties of the nebulized liquid, it can be adjusted by adding some compounds as viscosity modifiers (VMs) of a liquid drug. Natural polysaccharides have been recently proposed for this purpose and while they are biocompatible and generally recognized as safe (GRAS), their direct influence of the pulmonary structures is unknown. This work studied the direct influence of three natural VMs (sodium hyaluronate, xanthan gum, and agar) on the surface activity of the pulmonary surfactant (PS) measured in vitro using the oscillating drop method. The results allowed for comparing the variations of the dynamic surface tension during breathing-like oscillations of the gas/liquid interface with the PS, and the viscoelastic response of this system, as reflected by the hysteresis of the surface tension. The analysis was done using quantitative parameters, i.e., stability index (SI), normalized hysteresis area (
), and loss angle (
), depending on the oscillation frequency (
). It was also found that, typically, SI is in the range of 0.15-0.3 and increases nonlinearly with
, while
slightly decreases. The effect of NaCl ions on the interfacial properties of PS was noted, which was usually positive for the size of hysteresis with an
value up to 2.5 mN/m. All VMs in general were shown to have only a minor effect on the dynamic interfacial properties of PS, suggesting the potential safety of the tested compounds as functional additives in medical nebulization. The results also demonstrated relationships between the parameters typically used in the analysis of PS dynamics (i.e.,
and SI) and dilatational rheological properties of the interface, allowing for easier interpretation of such data.
The high rate of spreading of COVID-19 is attributed to airborne particles exhaled by infected but often asymptomatic individuals. In this review, the role of aerosols in SARS-CoV-2 coronavirus ...transmission is discussed from the biophysical perspective. The essential properties of the coronavirus virus transported inside aerosol droplets, their successive inhalation, and size-dependent deposition in the respiratory system are highlighted. The importance of face covers (respirators and masks) in the reduction of aerosol spreading is analyzed. Finally, the discussion of the physicochemical phenomena of the coronavirus entering the surface of lung liquids (bronchial mucus and pulmonary surfactant) is presented with a focus on a possible role of interfacial phenomena in pulmonary alveoli. Information given in this review should be important in understanding the essential biophysical conditions of COVID-19 infection via aerosol route as a prerequisite for effective strategies of respiratory tract protection, and possibly, indications for future treatments of the disease.
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