Recent advances in instrumentation for high-field Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) have enabled access to ∼70 000 unique molecular formulas in broadband mass ...spectral characterization of unfractionated/whole asphaltenes. The results accumulated over a decade highlight the need for an asphaltene molecular model that acknowledges the coexistence of (1) monofunctional and polyfunctional species; (2) island and archipelago structural motifs; and (3) heteroatom-depleted/highly aromatic compounds, as well as atypical species with low aromaticity but increased heteroatom content. Collectively, results from FT-ICR MS, preparatory-scale separations (extrography/interfacial material), gel permeation chromatography, precipitation behavior in heptane:toluene, thermal decomposition, and aggregate microstructure by atomic force microscopy (among other techniques), suggest that the strong aggregation of asphaltenes results from the synergy between several intermolecular forces: π-stacking, hydrogen bonding, London forces, and acid/base interactions. This review presents general features of asphaltene molecular composition reported over the past five decades. We focus on mass spectrometry characterization and expose the reasons why early results supported the dominance of single-core motifs. Then, the discussion shifts to recent advances in instrumentation for high-field FT-ICR MS, which have enabled the detection of thousands of species in asphaltene samples, whose molecular composition and fragmentation behavior in ultrahigh vacuum agree with the coexistence of single-core and multicore structural motifs. Furthermore, evidence that highlights the limitations of commercially available/custom-built ion sources and selective ionization effects is presented. Consequently, the limitations require separations (e.g., chromatography, extrography) to gain more-comprehensive molecular-level insights into the composition of these complex organic mixtures. The final sections present evidence for the role of aggregation in selective ionization and suggest that advanced characterization by both thermal desorption/decomposition and liquid chromatography with online FT-ICR MS detection can be employed to mitigate the effects of aggregation and provide unique insights in molecular composition/structure.
The search for potential biomarkers of psychiatric disorders is a central topic in biological psychiatry. This review concerns published studies on potential biomarkers of treatment-resistant ...depression (TRD). The search for biomarkers of TRD in the bloodstream has focused on cytokines and steroids as well as brain-derived neurotropic factor. Additional approaches to identifying biomarkers of TRD have dealt with cerebrospinal fluid analysis, magnetic resonance imaging, and positron emission tomography. Some studies have also investigated potential genetic and epigenetic factors in TRD. Most studies have, however, used a post hoc experimental design that failed to determine the association between biomarkers and the initial risk of TRD. Particular attention in future studies should be on shifting the experimental paradigm toward procedures that can determine the risk for developing treatment resistance in untreated depressed individuals.
Proton-transfer reactions (PTRs) have emerged as a powerful tool for the study of intact proteins. When coupled with m/z-selective kinetic excitation, such as parallel ion parking (PIP), one can ...exert exquisite control over rates of reaction with a high degree of specificity. This allows one to “concentrate”, in the gas phase, nearly all the signals from an intact protein charge state envelope into a single charge state, improving the signal-to-noise ratio (S/N) by 10× or more. While this approach has been previously reported, here we show that implementing these technologies on a 21 T FT-ICR MS provides a tremendous advantage for intact protein analysis. Advanced strategies for performing PTR with PIP were developed to complement this unique instrument, including subjecting all analyte ions entering the mass spectrometer to PTR and PIP. This experiment, which we call “PTR-MS1-PIP”, generates a pseudo-MS1 spectrum derived from ions that are exposed to the PTR reagent and PIP waveforms but have not undergone any prior true mass filtering or ion isolation. The result is an extremely rapid and significant improvement in the spectral S/N of intact proteins. This permits the observation of many more proteoforms and reduces ion injection periods for subsequent tandem mass spectrometry characterization. Additionally, the product ion parking waveform has been optimized to enhance the PTR rate without compromise to the parking efficiency. We demonstrate that this process, called “rapid park”, can improve reaction rates by 5–10× and explore critical factors discovered to influence this process. Finally, we demonstrate how coupling PTR-MS1 and rapid park provides a 10-fold reduction in ion injection time, improving the rate of tandem MS sequencing.
Mass spectrometry imaging has become a popular tool for probing the chemical complexity of biological surfaces. This led to the development of a wide range of instrumentation and preparation ...protocols. It is thus desirable to evaluate and compare the data output from different methodologies and mass spectrometers. Here, we present an approach for the comparison of mass spectrometry imaging data from different laboratories (often referred to as multicenter studies). This is exemplified by the analysis of mouse brain sections in five laboratories in Europe and the USA. The instrumentation includes matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF), MALDI-QTOF, MALDI-Fourier transform ion cyclotron resonance (FTICR), atmospheric-pressure (AP)-MALDI-Orbitrap, and cluster TOF-secondary ion mass spectrometry (SIMS). Experimental parameters such as measurement speed, imaging bin width, and mass spectrometric parameters are discussed. All datasets were converted to the standard data format imzML and displayed in a common open-source software with identical parameters for visualization, which facilitates direct comparison of MS images. The imzML conversion also allowed exchange of fully functional MS imaging datasets between the different laboratories. The experiments ranged from overview measurements of the full mouse brain to detailed analysis of smaller features (depending on spatial resolution settings), but common histological features such as the corpus callosum were visible in all measurements. High spatial resolution measurements of AP-MALDI-Orbitrap and TOF-SIMS showed comparable structures in the low-micrometer range. We discuss general considerations for planning and performing multicenter studies in mass spectrometry imaging. This includes details on the selection, distribution, and preparation of tissue samples as well as on data handling. Such multicenter studies in combination with ongoing activities for reporting guidelines, a common data format (imzML) and a public data repository can contribute to more reliability and transparency of MS imaging studies.
Comparison of MS imaging platforms in international multicenter study
Petroleum derived dissolved organic matter (DOM
HC
) samples were successfully cationized with barium, revealing many M-H + Ba
+
peaks in both dark and simulated sunlight treatments. The DOM
HC
...samples generated after light exposure exhibited a greater number of M-H + Ba
+
peaks compared to the dark control. Multiple M-H + Ba
+
peaks were investigated in the irradiated DOM
HC
using low resolution MS/MS in order to confirm the presence of diagnostic fragment ions,
m
/
z
139, 155 and 196 in each treatment. Due to the high complexity of the bariated DOM
HC
mixture, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS/MS) was employed to obtain molecular level information for both irradiated and dark treatments. The irradiated DOM
HC
treatments had more bariated oxygenated species over a wide range of H/C and O/C when compared to the dark controls. Doubly bariated species were also observed in DOM
HC
, which provides evidence that photochemistry transforms DOM
HC
to even more complex mixtures with multiple oxygenations per molecule. This study provides evidence that barium adduct mass spectrometry can be successfully applied to DOM
HC
screening for the presence of COOHs, both in dark samples and solar irradiated samples. Furthermore, direct evidence and molecular composition of aqueous phase crude oil photoproducts is provided by this technique.
Photochemistry plays a role in the dissolution of petroleum derived carboxylic acids.
Globally, groundwater represents a critical natural resource that is affected by changes in natural supply and renewal, as well as by increasing human demand and consumption. However, despite its ...critical role, groundwater is difficult to accurately quantify as it is beneath the Earth surface. Here, we review several state‐of‐the‐art remote sensing techniques useful for local‐ to global‐scale groundwater monitoring and assessment, including proxies for groundwater extraction. These include inferring changes in subsurface water from mass changes using gravitational measurements, and analyzing changes in the Earth surface height using Interferometric Synthetic Aperture Radar, Light Detection and Ranging, Airborne Electromagnetic Systems, and satellite altimetry. Remote sensing information is often used in tandem with ground‐based observations such as hydraulic head in wells, Global Navigational Satellite System monitoring, and numerical modeling to complement the space‐based approaches. In the future, fusing different remote sensing techniques capable of operating in various environments will yield additional insight on the state and rate of use for groundwater across the globe.
Key Points
Accurately measuring and monitoring groundwater storage and fluxes is critical for water, food, and energy security
Remote sensing approaches such as gravitational measurements, Interferometric Synthetic Aperture Radar, Global Navigational Satellite System, lidar altimetry, and Airborne Electromagnetic Systems can yield indirect yet valuable information about groundwater
Fusing multiple remotely sensed data sets or employing other tools such as numerical models increase the applicability of individual approaches
We report the discovery of an extraordinarily massive young cluster of stars in the Galaxy, having an inferred total initial cluster mass comparable to the most massive young clusters in the Galaxy. ...Using IRMOS, 2MASS, and Spitzer observations, we conclude that there are 14 red supergiants in the cluster, compared with five, in what was previously thought to be the richest Galactic cluster of such stars. We infer spectral types from near-infrared spectra that reveal deep CO bandhead absorption that can only be fit by red supergiants. We identify a gap of K sub(s) 6 4 mag between the stars and the bulk of the other stars in the region that can only be fit by models if the brightest stars in the cluster are red supergiants. We estimate a distance of 5.8 kpc to the cluster by associating an OH maser with the envelope of one of the stars. We also identify a "yellow" supergiant of G6 I type in the cluster. Assuming a Salpeter IMF, we infer an initial cluster mass of 20,000-40,000 M sub(z) for cluster ages of 7-12 Myr. Continuing with these assumptions, we find that 80% of the initial mass and 99% of the number of stars remain at the present time. We associate the cluster with an X-ray source (detected by ASCA and Einstein), a recently discovered very high energy g-ray source (detected by INTEGRAL and HESS), and several nonthermal radio sources, finding that these objects are likely related to recent supernovae in the cluster. In particular, we claim that the cluster has produced at least one recent supernova remnant with properties similar to the Crab Nebula.
Non-obstructive azoospermia (NOA), the lack of spermatozoa in semen due to impaired spermatogenesis affects nearly 1% of men. In about half of cases, an underlying cause for NOA cannot be identified. ...This study aimed to identify novel variants associated with idiopathic NOA. We identified a nonconsanguineous family in which multiple sons displayed the NOA phenotype. We performed whole-exome sequencing in three affected brothers with NOA, their two unaffected brothers and their father, and identified compound heterozygous frameshift variants (one novel and one extremely rare) in Telomere Repeat Binding Bouquet Formation Protein 2 (
TERB2
) that segregated perfectly with NOA. TERB2 interacts with TERB1 and Membrane Anchored Junction Protein (MAJIN) to form the tripartite meiotic telomere complex (MTC), which has been shown in mouse models to be necessary for the completion of meiosis and both male and female fertility. Given our novel findings of
TERB2
variants in NOA men, along with the integral role of the three MTC proteins in spermatogenesis, we subsequently explored exome sequence data from 1495 NOA men to investigate the role of MTC gene variants in spermatogenic impairment. Remarkably, we identified two NOA patients with likely damaging rare homozygous stop and missense variants in
TERB1
and one NOA patient with a rare homozygous missense variant in
MAJIN
. Available testis histology data from three of the NOA patients indicate germ cell maturation arrest, consistent with mouse phenotypes. These findings suggest that variants in MTC genes may be an important cause of NOA in both consanguineous and outbred populations.
Laser ablation ESI (LAESI) is a recent development in MS imaging. It has been shown that lipids and small metabolites can be imaged in various samples such as plant material, tissue sections or ...bacterial colonies without any sample pretreatment. Further, LAESI has been shown to produce multiply charged protein ions from liquids or solid surfaces. This presents a means to address one of the biggest challenges in MS imaging; the identification of proteins directly from biological tissue surfaces. Such identification is hindered by the lack of multiply charged proteins in common MALDI ion sources and the difficulty of performing tandem MS on such large, singly charged ions. We present here top‐down identification of intact proteins from tissue with a LAESI ion source combined with a hybrid ion‐trap FT‐ICR mass spectrometer. The performance of the system was first tested with a standard protein with electron capture dissociation and infrared multiphoton dissociation fragmentation to prove the viability of LAESI FT‐ICR for top‐down proteomics. Finally, the imaging of a tissue section was performed, where a number of intact proteins were measured and the hemoglobin α chain was identified directly from tissue using CID and infrared multiphoton dissociation fragmentation.
Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of ...270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.
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