Petroleomics: Chemistry of the underworld Marshall, Alan G; Rodgers, Ryan P
Proceedings of the National Academy of Sciences - PNAS,
11/2008, Letnik:
105, Številka:
47
Journal Article
Recenzirano
Odprti dostop
Each different molecular elemental composition--e.g., CcHhNnOoSs--has a different exact mass. With sufficiently high mass resolving power (m/Δm₅₀% almost equal to 400,000, in which m is molecular ...mass and Δm₅₀% is the mass spectral peak width at half-maximum peak height) and mass accuracy (<300 ppb) up to almost equal to800 Da, now routinely available from high-field (greater-than-or-equal9.4 T) Fourier transform ion cyclotron resonance mass spectrometry, it is possible to resolve and identify uniquely and simultaneously each of the thousands of elemental compositions from the most complex natural organic mixtures, including petroleum crude oil. It is thus possible to separate and sort petroleum components according to their heteroatom class (NnOoSs), double bond equivalents (DBE = number of rings plus double bonds involving carbon, because each ring or double bond results in a loss of two hydrogen atoms), and carbon number. "Petroleomics" is the characterization of petroleum at the molecular level. From sufficiently complete characterization of the organic composition of petroleum and its products, it should be possible to correlate (and ultimately predict) their properties and behavior. Examples include molecular mass distribution, distillation profile, characterization of specific fractions without prior extraction or wet chemical separation from the original bulk material, biodegradation, maturity, water solubility (and oil:water emulsion behavior), deposits in oil wells and refineries, efficiency and specificity of catalytic hydroprocessing, "heavy ends" (asphaltenes) analysis, corrosion, etc.
A PERSONAL SCIENTIFIC HISTORY Marshall, Alan G.
Mass spectrometry reviews,
March/April 2022, 2022-03-00, 20220301, Letnik:
41, Številka:
2
Journal Article
Lysyl-tRNA synthetase (LysRS), a component of the translation apparatus, is released from the cytoplasmic multi-tRNA synthetase complex (MSC) to activate the transcription factor MITF in stimulated ...mast cells through undefined mechanisms. Here we show that Ser207 phosphorylation provokes a new conformer of LysRS that inactivates its translational function but activates its transcriptional function. The crystal structure of an MSC subcomplex established that LysRS is held in the MSC by binding to the N terminus of the scaffold protein p38/AIMP2. Phosphorylation-created steric clashes at the LysRS domain interface disrupt its binding grooves for p38/AIMP2, releasing LysRS and provoking its nuclear translocation. This alteration also exposes the C-terminal domain of LysRS to bind to MITF and triggers LysRS-directed production of the second messenger Ap4A that activates MITF. Thus our results establish that a single conformational change triggered by phosphorylation leads to multiple effects driving an exclusive switch of LysRS function from translation to transcription.
Display omitted
► Phosphorylation of Ser207 triggers a structural opening of LysRS in mast cell ► The open conformer releases LysRS from the multi-tRNA-synthetase complex ► It traps tRNA in an inactive state and switches off the canonical function of LysRS ► It drives Ap4A production and LysRS-MITF interaction for gene transcription in cell
High Resolution Mass Spectrometry Xian, Feng; Hendrickson, Christopher L; Marshall, Alan G
Analytical chemistry (Washington),
01/2012, Letnik:
84, Številka:
2
Journal Article
•IHSS Pony Lake and Suwannee River fulvic acid DOM reference samples compared.•Molecular constituents assigned and characterized using FT-ICR MS.•Complementary data obtained from fluorescence ...spectroscopy.•Proteinaceous signatures of Pony Lake DOM assigned from both analytical methods.•More reactive/microbial character for Pony Lake DOM than for Suwannee River DOM.
We present the extensive characterization of Antarctic Pony Lake (PL) dissolved organic matter (DOM), an International Humic Substance Society (IHSS) fulvic acid (FA) reference standard, using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) and excitation–emission matrix fluorescence spectroscopy (EEMS). PLFA is the first reference standard available through IHSS derived solely from a microbial source. A number of factors differentiate PLFA from other IHSS standards, including source material, geographic location, sunlight exposure, freeze–thaw conditions, and other in situ environmental influences. ESI FT-ICR MS and EEMS were used to compare the PLFA microbial DOM compositional signature with the IHSS Suwannee River (SR) FA, a standard frequently studied for environmental DOM analysis. Although CcHhOoNnSs (n=0, 1, or 2 and s=0 or 1) constituents were present in both IHSS samples, PLFA contained more N and S molecular species, whereas SRFA was dominated by CcHhOo compounds. Proteinaceous character was detected with both methods, in greater abundance for PLFA, which we attributed to its microbial source material and labile, potentially more reactive nature than SRFA. Characterization from both analytical techniques resulted in complementary data that reinforce the importance of PLFA as an IHSS reference standard that should be utilized for other microbiological environmental DOM comparisons.
We describe the design and initial performance of the first 21 tesla Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. The 21 tesla magnet is the highest field superconducting ...magnet ever used for FT-ICR and features high spatial homogeneity, high temporal stability, and negligible liquid helium consumption. The instrument includes a commercial dual linear quadrupole trap front end that features high sensitivity, precise control of trapped ion number, and collisional and electron transfer dissociation. A third linear quadrupole trap offers high ion capacity and ejection efficiency, and rf quadrupole ion injection optics deliver ions to a novel dynamically harmonized ICR cell. Mass resolving power of 150,000 (
m/Δm
50%
) is achieved for bovine serum albumin (66 kDa) for a 0.38 s detection period, and greater than 2,000,000 resolving power is achieved for a 12 s detection period. Externally calibrated broadband mass measurement accuracy is typically less than 150 ppb rms, with resolving power greater than 300,000 at
m/z
400 for a 0.76 s detection period. Combined analysis of electron transfer and collisional dissociation spectra results in 68% sequence coverage for carbonic anhydrase. The instrument is part of the NSF High-Field FT-ICR User Facility and is available free of charge to qualified users.
Graphical Abstract
ᅟ
Ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry has recently revealed that petroleum crude oil contains heteroatom-containing (N,O,S) organic components having more ...than 20 000 distinct elemental compositions (C c H h N n O o S s ). It is therefore now possible to contemplate the ultimate characterization of all of the chemical constituents of petroleum, along with their interactions and reactivity, a concept we denote as “petroleomics”. Such knowledge has already proved capable of distinguishing petroleum and its distillates according to their geochemical origin and maturity, distillation cut, extraction method, catalytic processing, etc. The key features that have opened up this new field have been (a) ultrahigh-resolution FT-ICR mass analysis, specifically, the capability to resolve species differing in elemental composition by C3 vs SH4 (i.e., 0.0034 Da); (b) higher magnetic field to cover the whole mass range at once; (c) dynamic range extension by external mass filtering; and (d) plots of Kendrick mass defect vs nominal Kendrick mass as a means for sorting different compound “classes” (i.e., numbers of N, O, and S atoms), “types” (rings plus double bonds), and alkylation ((−CH2) n ) distributions, thereby extending to >900 Da the upper limit for unique assignment of elemental composition based on accurate mass measurement. The same methods are also being applied successfully to analysis of humic and fulvic acids, coals, and other complex natural mixtures, often without prior or on-line chromatographic separation.
Background & Aims Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent desmoplastic microenvironment that contains many different immune cells. Activated pancreatic stellate cells ...(PSCs) contribute to the desmoplasia. We investigated whether distinct stromal compartments are differentially infiltrated by different types of immune cells. Methods We used tissue microarray analysis to compare immune cell infiltration of different pancreaticobiliary diseased tissues (PDAC, ampullary carcinoma, cholangiocarcinoma, mucinous cystic neoplasm, chronic inflammation, and chronic pancreatitis) and juxtatumoral stromal (<100 μm from tumor) and panstromal compartments. We investigated the association between immune infiltrate and patient survival times. We also analyzed T-cell migration and tumor infiltration in LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) mice and the effects of all-trans retinoic acid (ATRA) on these processes. Results Juxtatumoral compartments in PDAC samples from 2 independent groups of patients contained increased numbers of myeloperoxidase+ and CD68+ cells compared with panstromal compartments. However, juxtatumoral compartments of PDACs contained fewer CD8+ , FoxP3+ , CD56+ , or CD20+ cells than panstromal compartments, a distinction absent in ampullary carcinomas and cholangiocarcinomas. Patients with PDACs that had high densities of CD8+ T cells in the juxtatumoral compartment had longer survival times than patients with lower densities. In KPC mice, administration of ATRA, which renders PSCs quiescent, increased numbers of CD8+ T cells in juxtatumoral compartments. We found that activated PSCs express cytokines, chemokines, and adhesion molecules that regulate T-cell migration. In vitro migration assays showed that CD8+ T cells, from patients with PDAC, had increased chemotaxis toward activated PSCs, which secrete CXCL12, compared with quiescent PSCs or tumor cells. These effects could be reversed by knockdown of CXCL12 or treatment of PSCs with ATRA. Conclusions Based on studies of human PDAC samples and KPC mice, activated PSCs appear to reduce migration of CD8+ T cells to juxtatumoral stromal compartments, preventing their access to cancer cells. Deregulated signaling by activated PSCs could prevent an effective antitumor immune response.
Here, we present atmospheric pressure photoionization (APPI) Fourier transform ion cyclotron resonance (FTICR) mass analysis of a volcanic asphalt sample by acquiring data for 20 Da wide mass ...segments across a 1000 Da range, stitched into a single composite mass spectrum, and compare to a broad-band mass spectrum for the same sample. The segmented spectrum contained 170 000 peaks with magnitude greater than 6σ of the root-mean-square (rms) baseline noise, for which 126 264 unique elemental compositions could be assigned. Approximately two-thirds of those compositions represent monoisotopic (i.e., chemically different) species. That complexity is higher than that for any previously reported mass spectrum and almost 3 times greater than that obtained from the corresponding broad-band spectrum (59 015). For the segmented mass spectrum, the signal-to-noise ratio (S/N) was significantly higher throughout the spectrum, but especially at the lower and upper ends of mass distribution relative to that of the near-Gaussian broad-band mass distribution. Despite this S/N improvement, mass measurement accuracy was noticeably improved only at lower masses. The increased S/N did, however, yield a higher number of peaks and higher dynamic range throughout the entire segmented spectrum relative to the conventional broad-band spectrum. The additional assigned peaks include higher heteroatom species, as well as additional radicals and isotopologues. Segmenting can require a significant investment in data acquisition and analysis time over broad-band spectroscopy (∼1775% in this case) making it best suited for targeted analysis and/or when complete compositional coverage is important. Finally, the present segmented spectrum contains, to our knowledge, more assigned peaks than any spectrum of any kind (e.g., UV–vis, infrared, microwave, magnetic resonance, etc.).
PDF
