Mosaic of Somatic Mutations in Earth's Oldest Living Organism, Pando.

Understanding how mutations arise and spread through individuals and populations is fundamental to evolutionary biology. Most organisms have a life cycle with unicellular bottlenecks during reproduction. However, some organisms like plants, fungi, or colonial animals can grow indefinitely, changing the manner in which mutations spread throughout both the individual and the population.

Spreading Standardized Documentation of Pediatric Occupational and Physical Therapy Dose: A Quality Improvement Initiative.

Importance: Clinicians and researchers can leverage clinical documentation of therapy services for quality improvement and research purposes. However, documentation is often institution specific and may not adequately capture the dose of therapy delivered, thus limiting collaboration.

Objective: To implement documentation of pediatric occupational and physical therapy dose from one institution to another institution.

Time-of-flight secondary ion mass spectrometry imaging in cultural heritage: A focus on old paintings.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging is a surface analysis technique that identifies and spatially resolves the chemical composition of a sample with a lateral resolution of less than 1 μm. Depth analyses can also be performed over thicknesses of several microns. In the case of a painting cross section, for example, TOF-SIMS can identify the organic composition, by detecting molecular ions and fragments of binders, as well as the mineral composition of most of the pigments.

TOF-SIMS Imaging of Biological Tissue Sections and Structural Determination Using Tandem MS.

Over the past couple of years, imaging mass spectrometry (IMS) has arisen as a powerful tool to answer research questions in the biomedical field. Imaging mass spectrometry allows for label-free chemical imaging by providing full molecular information. The IMS technique best positioned for cell and tissue analysis is time-of-flight secondary ion mass spectrometry (ToF-SIMS) because it has the best spatial resolution of all the molecular IMS techniques and can detect many biochemical species and especially lipids with high sensitivity.

Time-of-Flight Secondary Ion Mass Spectrometry Imaging of Cross Sections from the Bacchanals Paintings of Nicolas Poussin.

The two paintings Infant Bacchanals (Museo Nazionale d'Arte Antica, Palazzo Barberini, Rome, Italy) executed by Nicolas Poussin (Les Andelys, 1594-Rome, 1665) in around 1626 are thought to have been painted "a guazzo", which means either with a glue or with an egg binding medium. To date, this has never been confirmed through analysis. Dual-beam time-of-flight secondary ion mass spectrometry (TOF-SIMS), using a bismuth cluster liquid metal ion gun and an argon gas cluster ion beam, allows the mapping of organic and inorganic matter on paintings cross sections, with the possibility to acquire submicrometer-resolution mass spectrometry images of the sample, together with high mass resolution using a delayed extraction of secondary ions.

The European Reference Network for Rare Neurological Diseases.

While rare diseases (RDs) are by definition of low prevalence, the total number of patients suffering from an RD is high, and the majority of them have neurologic manifestations, involving central, peripheral nerve, and muscle. In 2017, 24 European Reference Networks (ERNs), each focusing on a specific group of rare or low-prevalence complex diseases, were formed to improve the care for patients with an RD. One major aim is to have "the knowledge travel instead of the patient," which has been put into practice by the implementation of the Clinical Patient Management System (CPMS) that enables clinicians to perform pan-European virtual consultations.

Narrow Aperture Detection Electrodes ICR Cell with Quadrupolar Ion Detection for FT-ICR MS at the Cyclotron Frequency.

Ion signal detection at the true (unperturbed) cyclotron frequency instead of the conventional reduced cyclotron frequency has remained a formidable challenge since the inception of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Recently, routine FT-ICR MS at the true cyclotron frequency has become a reality with the implementation of ICR cells with narrow aperture detection electrodes (NADEL). Here, we describe the development and implementation of the next generation of these cells, namely, a 2xNADEL ICR cell, which comprises four flat detect and four ∼45° cylindrical excite electrodes, enabling independent ion excitation and quadrupolar ion detection.

Multimodal Imaging Mass Spectrometry to Identify Markers of Pulmonary Arterial Hypertension in Human Lung Tissue Using MALDI-ToF, ToF-SIMS, and Hybrid SIMS.

Pulmonary arterial hypertension (PAH) is a rare and deadly disease affecting roughly 15-60 people per million in Europe with a poorly understood pathology. There are currently no diagnostic tools for early detection nor does a curative treatment exist. The lipid composition of arteries in lung tissue samples from human PAH and control patients were investigated using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) combined with time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging.

Stable or seral? Fire-driven alternative states in aspen forests of western North America.

As important centres for biological diversity, aspen forests are essential to the function and aesthetics of montane ecosystems in western North America. Aspen stands are maintained by a nuanced relationship with wildfire, although in recent decades aspen mortality has increased. The need to understand the baseline environmental conditions that favour aspen is clear; however, long-term fire history reconstructions are rare due to the scarcity of natural archives in dry montane settings.

Kidney Lipidomics by Mass Spectrometry Imaging: A Focus on the Glomerulus.

Lipid disorders have been associated with glomerulopathies, a distinct type of renal pathologies, such as nephrotic syndrome. Global analyses targeting kidney lipids in this pathophysiologic context have been extensively performed, but most often regardless of the architectural and functional complexity of the kidney. The new developments in mass spectrometry imaging technologies have opened a promising field in localized lipidomic studies focused on this organ.

Biosynthetic investigation of γ-lactones in Sextonia rubra wood using in situ TOF-SIMS MS/MS imaging to localize and characterize biosynthetic intermediates.

Molecular analysis by parallel tandem mass spectrometry (MS/MS) imaging contributes to the in situ characterization of biosynthetic intermediates which is crucial for deciphering the metabolic pathways in living organisms. We report the first use of TOF-SIMS MS/MS imaging for the cellular localization and characterization of biosynthetic intermediates of bioactive γ-lactones rubrynolide and rubrenolide in the Amazonian tree Sextonia rubra (Lauraceae). Five γ-lactones, including previously reported rubrynolide and rubrenolide, were isolated using a conventional approach and their structural characterization and localization at a lateral resolution of ~400 nm was later achieved using TOF-SIMS MS/MS imaging analysis.

Internal Energy Distribution of Secondary Ions Under Argon and Bismuth Cluster Bombardments: "Soft" Versus "Hard" Desorption-Ionization Process.

The emission/ionization process under massive argon cluster bombardment was investigated by measuring the internal energy distributions of a series of benzylpyridinium ions. Argon clusters with kinetic energies between 10 and 20 keV and cluster sizes ranging from 500 to 10,000 were used to establish the influence of their size, energy, and velocity on the internal energy distribution of the secondary ions. It is shown that the internal energy distribution of secondary ions principally depends on the energy per atom or the velocity of the cluster ion beam (E/n ∝ v).

Abiotic synthesis of amino acids in the recesses of the oceanic lithosphere.

Abiotic hydrocarbons and carboxylic acids are known to be formed on Earth, notably during the hydrothermal alteration of mantle rocks. Although the abiotic formation of amino acids has been predicted both from experimental studies and thermodynamic calculations, its occurrence has not been demonstrated in terrestrial settings. Here, using a multimodal approach that combines high-resolution imaging techniques, we obtain evidence for the occurrence of aromatic amino acids formed abiotically and subsequently preserved at depth beneath the Atlantis Massif (Mid-Atlantic Ridge).

Tandem Mass Spectrometry Imaging and in Situ Characterization of Bioactive Wood Metabolites in Amazonian Tree Species Sextonia rubra.

Driven by a necessity for confident molecular identification at high spatial resolution, a new time-of-flight secondary ion mass spectrometry (TOF-SIMS) tandem mass spectrometry (tandem MS) imaging instrument has been recently developed. In this paper, the superior MS/MS spectrometry and imaging capability of this new tool is shown for natural product study. For the first time, via in situ analysis of the bioactive metabolites rubrynolide and rubrenolide in Amazonian tree species Sextonia rubra (Lauraceae), we were able both to analyze and to image by tandem MS the molecular products of natural biosynthesis.

Radial distribution of wood extractives in European larch Larix decidua by TOF-SIMS imaging.

Wood extractives in the xylem of European larch Larix decidua were mapped by time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging, which allows the radial distribution of both mineral and lipophilic extractives in the xylem to be scrutinized with high spatial resolution for the first time. Results show that all the components are inhomogeneously distributed across the annual ring. Mineral nutrients including Na, K, Ca, and Cl ions exhibit no preferential localization between earlywood and latewood, whereas PO ion is exclusively present in the ray cells, indicating it may be related to acid phosphatase.

Long-term hypoxia uncouples Ca and eNOS in bradykinin-mediated pulmonary arterial relaxation.

Bradykinin-induced activation of the pulmonary endothelium triggers a rise in intracellular Ca that activates nitric oxide (NO)-dependent vasorelaxation. Chronic hypoxia is commonly associated with increased pulmonary vascular tone, which can cause pulmonary hypertension in responsive individuals. In the present study, we tested the hypothesis that long-term high-altitude hypoxia (LTH) diminishes bradykinin-induced Ca signals and inhibits endothelial nitric oxide synthase (eNOS), prostacyclin (PGI), and large-conductance K (BK) channels in sheep, which are moderately responsive to LTH, resulting in decreased pulmonary arterial vasorelaxation.

Insights into the MALDI Process after Matrix Deposition by Sublimation Using 3D ToF-SIMS Imaging.

Imaging mass spectrometry (IMS) has become a powerful tool to characterize the spatial distribution of biomolecules in thin tissue sections. In the case of matrix-assisted laser desorption ionization (MALDI) IMS, homogeneous matrix deposition is critical to produce high-quality ion images, and sublimation in particular has shown to be an excellent matrix deposition method for the imaging of lipids. Matrix deposition by sublimation is, however, a completely solvent-free system, which ought to prevent the mixing of matrix and analytes thought to be necessary for successful MALDI.

Long-term high-altitude hypoxia influences pulmonary arterial L-type calcium channel-mediated Ca signals and contraction in fetal and adult sheep.

Long-term hypoxia (LTH) has a profound effect on pulmonary arterial vasoconstriction in the fetus and adult. Dysregulation in Ca signaling is important during the development of LTH-induced pulmonary hypertension. In the present study, we tested the hypothesis that L-type Ca channels (Ca), which are voltage dependent and found in smooth, skeletal, and cardiac muscle, are important in the adaptation of pulmonary arterial contractions in postnatal maturation and in response to LTH.

An Integrative Approach to Decipher the Chemical Antagonism between the Competing Endophytes Paraconiothyrium variabile and Bacillus subtilis.

An integrative approach combining traditional natural products chemistry, molecular networking, and mass spectrometry imaging has been undertaken to decipher the molecular dialogue between the fungus Paraconiothyrium variabile and the bacterium Bacillus subtilis, which were isolated as endophytes from the conifer Cephalotaxus harringtonia and are characterized by a strong and mutual antibiosis. From this study, we highlight that bacterial surfactins and a fungal tetronic acid are involved in such competition and that the fungus is able to hydrolyze surfactins to fight against the bacterial partner.

Electrospun thermosensitive hydrogel scaffold for enhanced chondrogenesis of human mesenchymal stem cells.

Unlabelled: Hydrogels have shown great potential for cartilage tissue engineering applications due to their capability to encapsulate cells within biomimetic, 3-dimensional (3D) microenvironments. However, the multi-step fabrication process that is necessary to produce cell/scaffold constructs with defined dimensions, limits their off-the-shelf translational usage. In this study, we have developed a hybrid scaffolding system which combines a thermosensitive hydrogel, poly(ethylene glycol)-poly(N-isopropylacrylamide) (PEG-PNIPAAm), with a biodegradable polymer, poly(ε-caprolactone) (PCL), into a composite, electrospun microfibrous structure.

Correlative mass spectrometry imaging, applying time-of-flight secondary ion mass spectrometry and atmospheric pressure matrix-assisted laser desorption/ionization to a single tissue section.

Rationale: Mass spectrometry imaging (MSI) is a powerful tool for mapping the surface of a sample. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) and atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) offer complementary capabilities. Here, we present a workflow to apply both techniques to a single tissue section and combine the resulting data for the example of human colon cancer tissue.

Environmentally Friendly Procedure Based on Supercritical Fluid Chromatography and Tandem Mass Spectrometry Molecular Networking for the Discovery of Potent Antiviral Compounds from Euphorbia semiperfoliata.

A supercritical fluid chromatography-based targeted purification procedure using tandem mass spectrometry and molecular networking was developed to analyze, annotate, and isolate secondary metabolites from complex plant extract mixture. This approach was applied for the targeted isolation of new antiviral diterpene esters from Euphorbia semiperfoliata whole plant extract. The analysis of bioactive fractions revealed that unknown diterpene esters, including jatrophane esters and phorbol esters, were present in the samples.

Using Paleoecology to Inform Land Management as Climates Change: An Example from an Oak Savanna Ecosystem.

Oak savanna, a transitional ecosystem between open prairie and dense oak forest, was once widespread in Minnesota. Upon European settlement much of the oak savanna was destroyed. Recently, efforts to restore this ecosystem have increased and often include the reintroduction of fire.