From mass spectral features to molecules in molecular networks: a novel workflow for untargeted metabolomics.

In the context of untargeted metabolomics, molecular networking is a popular and efficient tool which organizes and simplifies mass spectrometry fragmentation data (LC-MS/MS), by clustering ions based on a cosine similarity score. However, the nature of the ion species is rarely taken into account, causing redundancy as a single compound may be present in different forms throughout the network. Taking advantage of the presence of such redundant ions, we developed a new method named MolNotator. Using the different ion species produced by a molecule during ionization (adducts, dimers, trimers, in-source fragments), a predicted molecule node (or neutral node) is created by triangulation, and ultimately computing the associated molecule calculated mass. These neutral nodes provide researchers with several advantages. Firstly, each molecule is then represented in its ionization context, connected to all produced ions and indirectly to some coeluted compounds, thereby also highlighting unexpected widely present adduct species. Secondly, the predicted neutrals serve as anchors to merge the complementary positive and negative ionization modes into a single network. Lastly, the dereplication is improved by the use of all available ions connected to the neutral nodes, and the computed molecular masses can be used for exact mass dereplication. MolNotator is available as a Python library and was validated using the lichen database spectra acquired on an Orbitrap, computing neutral molecules for >90% of the 156 molecules in the dataset. By focusing on actual molecules instead of ions, MolNotator greatly facilitates the selection of molecules of interest.

Aspergillus flavus originated pure compound as a potential antibacterial

Problem Background Penicillin was the first and most famous fungal secondary metabolite used as broad spectrum antibiotic that revolutionarised pharmaceutical research and also saved millions of lives. The over optimistic belief in 1967 that sufficient antibiotics had been discovered to defeat infectious diseases was quickly crashed with the appearance of multidrug resistant (MDR) bacteria in 1990s. This has posed a serious threat to mankind. Although scientists are making efforts to synthesize and discover new antibiotics there are not enough new drugs in pharmaceutical pipeline to beat the pace at which MDR bacteria are emerging. In view of this there is an urgent and serious medical need for new bioactive compounds to be discovered to treat infections caused by MDR pathogens. The present study is aimed to investigate the antibacterial potential of Aspergillus flavus originated compounds that may act as drug leads to treat future infections. Methodology Among the 6 isolated fungal strains from the rhizosphere of Mentha piperetta, one was processed for isolation of secondary metabolites on the basis of preliminary antibacterial testing. Observation of morphological and microscopic features helped in identification of the fungal strain as Aspergillus flavus. Potato Dextrose Agar (PDA) medium was used for fungal growth while Czapec Yeast Broth (CYB) medium was used for production of fungal metabolites. Column chromatography technique was utilized for purification of compound from crude fungal extract and the mass of the compound was determined using Liquid Chromatography Mass Spectrometry (LCMS) method. Structure elucidation of the pure compound was performed using 500 Varian Nuclear Magnetic Resonance (NMR) machine. Docking was performed using Glide SP algorithm. Agar well diffusion method was used to determine the invitro antibacterial potential of the compound against two MDR bacterial strains i.e. Staphylococcus aureus and Proteus vulgaris. For this a total of 4 dose concentrations i.e. (100, 250, 500, 1000 μg mL− 1) of the compound were prepared and applied to bacterial strains on Mueller Hinton agar using tetracycline as control. Results The chemical name of the purified compound from A. flavus was determined as (2E)-3-[(3S, 4R)-8-hydroxy-3, 4-dimethyl-1-oxo-3, 4-dihydro-1H-2- benzopyran-7-yl] prop-2-enoic acid with the formula C14H14O5 and exact mass of 262.08. The in-Silico analysis showed that this compound has the potential to inhibit the binding pocket of S. aureus TyrRS (1JII) with docking score of − 8.67 Kcal mole− 1. The results obtained from invitro experiments were encouraging as at 1000 μg mL− 1 the compound showed 58.8% inhibition against S. aureus and 28% inhibition against P. vulgaris. Conclusions The pure compound with formula C14H14O5 and exact mass of 262 exhibited antibacterial potential both insilico and invitro against both Gram negative and Gram positive bacteria. The compound was more active against S. aureus in comparison to P. vulgaris. From the obtained results it is concluded that this compound can be used as potent antibacterial candidate but further studies will be needed prior to its use as antibiotic.

A Fast and Automated Strategy for the Identification and Risk Assessment of Unknown Substances (IAS/NIAS) in Plastic Food Contact Materials by GC-Q-Orbitrap HRMS: Recycled LDPE as a Proof-of-Concept

A fast and automated approach has been developed for the tentative identification and risk assessment of unknown substances in plastic food contact materials (FCM) by GC-Q-Orbitrap HRMS. The proposed approach combines GC-HRMS full scan data acquisition coupled to Compound Discoverer™ 3.2 software for automated data processing and compound identification. To perform the tentative identification of the detected features, a restrictive set of identification criteria was used, including matching with the NIST Mass Spectral Library, exact mass of annotated fragments, and retention index calculation. After the tentative identification, a risk assessment of the identified substances was performed by using the threshold of toxicological concern (TTC) approach. This strategy has been applied to recycled low-density polyethylene (LDPE), which could be used as FCM, as a proof-of-concept demonstration. In the analyzed sample, 374 features were detected, of which 83 were tentatively identified after examination of the identification criteria. Most of these were additives, such as plasticizers, used in a wide variety of plastic applications, oligomers of LDPE, and substances with chemical, industrial, or cosmetic applications. The risk assessment was performed and, according to the TTC approach, the obtained results showed that there was no risk associated with the release of the identified substances. However, complementary studies related to the toxicity of the unidentified substances and the potential mixture toxicity (cocktail effects) should be conducted in parallel using bioassays.

Optimisation of the magistral semisolid formulations with furazidine used in urogenital infections

Background: Urinary tract infections are the most common urogenital diseases, with an increased incidence in men and older people. Urogenital infections are caused by Gram-negative bacteria, in which Escherichia coli predominates with a share of 80%. The evolution of microbial resistance to preparations used in curative-prophylactic institutions, induces the need of the reintroduction of nitrofurans, noteworthy for their wide spectrum of antibacterial activity. Material and methods: For the study, suppositories with furazidine were prepared by hand rolling and by melting and molding methods. Quantitative analysis was performed spectrophotometrically on a UV-VIS Perkin Elmer Lambda 40 spectrophotometer. All solvents and reagents had the degree of purity ”pure for analysis” and ”chemically pure”. Results: Duble cast method was applied to identify the exact mass of hydrophobic (cocoa butter, suppocire) and hydrophylic (polyethylene glycol mixtures) excipients. All the formulated suppositories were subjected to quality tests and showed acceptable physical characteristics and uniformity of drug contents. The UV-VIS spectrophotometric method for quantitiative determination of furazidine was developed and validated. The validation results showed that the developed method is simple, fast, accurate and robust. Conclusions: Suppositories with furazidine were prepared by classic technological methods. Preparation of the suppositories with furazidine on cocoa butter excipient is a suitable alternative for individual medicinal prescriptions. The UV-VIS spectrophotometric dosing method for furazidine in suppositories was developed and validated

Mechanical Synchronization of MEMS Electrostatically Driven Coupled Beam Filters

Micro-electromechanical systems (MEMS) bandpass filters based on arrays of electrostatically driven coupled beams have been demonstrated at MHz frequencies. High performance follows from the high Q-factor of mechanical resonators, and electrostatic transduction allows tuning, matching and actuation. For high-order filters, there is a conflict between the transduction mechanism and the coupling arrangement needed for dynamic synchronization: it is not possible to achieve synchronization and tuning simultaneously using a single voltage. Here we propose a general solution, based on the addition of mass-loaded beams at the ends of the array. These beams deflect for direct current (DC) voltages, and therefore allow electrostatic tuning, but do not respond to in-band alternating current (AC) voltages and hence do not interfere with synchronization. Spurious modes generated by these beams may be damped, leaving a good approximation to the desired response. The approach is introduced using a lumped element model and verified using stiffness matrix and finite element models for in-plane arrays with parallel plate drives and shown to be tolerant of the exact mass value. The principle may allow compensation of fabrication-induced variations in complex filters.

Tetrahedra of varying density and their applications

We propose concepts to utilize basic mathematical principles for computing the exact mass properties of objects with varying densities. For objects given as 3D triangle meshes, the method is analytically accurate and at the same time faster than any established approximation method. Our concept is based on tetrahedra as underlying primitives, which allows for the object’s actual mesh surface to be incorporated in the computation. The density within a tetrahedron is allowed to vary linearly, i.e., arbitrary density fields can be approximated by specifying the density at all vertices of a tetrahedral mesh. Involved integrals are formulated in closed form and can be evaluated by simple, easily parallelized, vector-matrix multiplications. The ability to compute exact masses and centroids for objects of varying density enables novel or more exact solutions to several interesting problems: besides the accurate analysis of objects under given density fields, this includes the synthesis of parameterized density functions for the make-it-stand challenge or manufacturing of objects with controlled rotational inertia. In addition, based on the tetrahedralization of Voronoi cells we introduce a precise method to solve $$L_{2|\infty }$$ L 2 | ∞ Lloyd relaxations by exact integration of the Chebyshev norm. In the context of additive manufacturing research, objects of varying density are a prominent topic. However, current state-of-the-art algorithms are still based on voxelizations, which produce rather crude approximations of masses and mass centers of 3D objects. Many existing frameworks will benefit by replacing approximations with fast and exact calculations. Graphic abstract

Leismanicidal Activity of Propolis Collected in the Semiarid Region of Brazil

Objective: The aim of the current study is to investigate the chemical composition, cytotoxic effect, and leishmanicidal activity of propolis collected in the semi-arid region of Bahia, Brazil.Methods: EtOH extract, hexane, EtOAc and MeOH fractions from propolis were analyzed by ultra-performance liquid chromatography coupled with diode array detector and quadrupole time-of-flight mass spectrometry. The identification was based on the exact mass, general fragmentation behaviors and UV absorption of the flavonoids. The in vitro cytotoxic effect and leishmanicidal activity of ethanolic extract, hexane, ethyl acetate, and methanolic fractions of propolis were evaluated.Results: Five triterpenes and twenty-four flavonoids were identified. The propolis did not present toxicity to the host cell up to the maximum concentration tested. In addition, all tested samples showed statistically significant activity against promastigotes of Leishmania chagasi and Leishmania amazonensis. Regarding the activity against amastigote forms of L. amazonensis, the hexane fraction, presented statistically significant activity with IC50 of 1.3 ± 0.1 μg/ml.Conclusion: The results support the idea that propolis can be used for future antileishmania studies.

Adaptive Wavelet Methods for Earth Systems Modelling

This paper reviews how dynamically adaptive wavelet methods can be designed to simulate atmosphere and ocean dynamics in both flat and spherical geometries. We highlight the special features that these models must have in order to be valid for climate modelling applications. These include exact mass conservation and various mimetic properties that ensure the solutions remain physically realistic, even in the under-resolved conditions typical of climate models. Particular attention is paid to the implementation of complex topography in adaptive models. Using wavetrisk as an example, we explain in detail how to build a semi-realistic global atmosphere or ocean model of interest to the geophysical community. We end with a discussion of the challenges that remain to developing a realistic dynamically adaptive atmosphere or ocean climate models. These include scale-aware subgrid scale parameterizations of physical processes, such as clouds. Although we focus on adaptive wavelet methods, many of the topics we discuss are relevant for adaptive mesh refinement (AMR).

Adaptive Wavelet Methods for Earth Systems Modelling

This paper reviews how dynamically adaptive wavelet methods can be designed to simulate atmosphere and ocean dynamics in both flat and spherical geometries. We highlight the special features that these models must have in order to be valid for climate modelling applications. These include exact mass conservation and various mimetic properties that ensure the solutions remain physically realistic, even in the under-resolved conditions typical of climate models. Particular attention is paid to the implementation of complex topography in adaptive models. Using \textsc{wavetrisk} as an example, we explain in detail how to build a semi-realistic global atmosphere or ocean model of interest to the geophysical community. We end with a discussion of the challenges that remain to developing a realistic dynamically adaptive atmosphere or ocean climate models. These include scale-aware subgrid scale parameterizations of physical processes, such as clouds. Although we focus on adaptive wavelet methods, many of the topics we discuss are relevant for adaptive mesh refinement (AMR).

Extractives in Betula celtiberica stemwood and isolation and identification of diarylheptanoids in the hydrophilic extract

In Betula celtiberica (Iberian white birch) stemwood, the content and composition of lipophilic and hydrophilic extractives were determined; these have not been reported previously in this species. The total gravimetric amount of extractives was 2.2% of dry wood, of which lipophilic extractives accounted for 0.39% and hydrophilic extractives 1.84% (determined by gas chromatography–flame ionisation detection [GC–FID]). The lipophilic extract contained mainly triterpenoids and steroids. The hydrophilic extract (acetone–water 95:5 v v−1) contained mainly sugars, compounds not eluting on GC, and a large number of unidentified compounds, which accounted for 0.87% of dry wood and dominated the extract. The compounds were isolated from the extract by silica column chromatography and further purified. GC–electron impact (EI)-MS of the silylated compounds showed characteristic mass fragments that suggested them to be diarylheptanoids (DAHs). This is an interesting compound group, as many of them have shown a large variety of beneficial biological effects. Of over 80 detected DAHs, the exact mass of 17 compounds was determined by electrospray ionisation-quadrupole-time-of-flight (ESI-QTOF)-MS, and of these, the structure of 11 compounds was elucidated by nuclear magnetic resonance (NMR). One was a meta,para-bridged diphenylether and 10 were meta,meta-bridged biphenyls, of which one, 3,8,9,17-tetrahydroxy-[7,0]-metacyclophane, has not been described previously. Because of low concentrations, 21 DAHs were only tentatively identified, and of these, as many as 17 seem to be previously undescribed compounds.