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Ying Yong Sheng Tai Xue Bao = the... Apr 2024Precipitation in the plum rain period accounts for 40%-50% of annual precipitation in the monsoon region. To clarify the temporal variability of the isotopic composition...
Precipitation in the plum rain period accounts for 40%-50% of annual precipitation in the monsoon region. To clarify the temporal variability of the isotopic composition of precipitation during the plum rain period from event to interannual time scale and identify the influencing factors, we analyzed the isotopic composition of precipitation and its influencing factors in Nanjing from 2015 to 2022. By using the Hybrid Single-particle Lagran-gian Integrated Trajectory (HYSPLIT) model with specific humidity analysis, we investigated the water vapor source and influencing factors. The results showed that 1) the isotopic abundance of atmospheric precipitation was depleted in the summer and enriched in winter. was lower in summer and higher in winter. The isotopic abundance of precipitation from the plum rain was depleted compared to mean value of the whole-year. 2) There was no significant correlation between δH and δO of the plum rain (precipitation) with local meteorological factors. However, was lower in light rain, reflecting the effect of sub-cloud evaporation. The average was higher during plum rain period in years with more total plum rain precipitation. 3) The low-latitude South China Sea and the western Pacific Ocean source area provided water vapor for the plum rain. The shift of moisture source region led to abrupt changes in precipitation isotopes. Our results could provide data support for studies on precipitation isotopes in the monsoon region, as well as a reference point for further understanding the precipitation mechanism of the plum rain and stu-dying the seasonal variability of atmospheric circulation in the East Asian monsoon region.
Topics: Rain; China; Seasons; Oxygen Isotopes; Environmental Monitoring; Deuterium; Isotopes; Prunus domestica
PubMed: 38884230
DOI: 10.13287/j.1001-9332.202404.017 -
Frontiers in Plant Science 2024The commonly used analytical tools for metabolomics cannot directly probe metabolic activities or distinguish metabolite differences between cells and suborgans in...
The commonly used analytical tools for metabolomics cannot directly probe metabolic activities or distinguish metabolite differences between cells and suborgans in multicellular organisms. These issues can be addressed by isotope labeling and mass spectrometry imaging (MSI), respectively, but the combination of the two, a newly emerging technology we call MSI, has been rarely applied to plant systems. In this study, we explored MSI of with DO labeling to study and visualize D-labeling in three classes of lipids: arabidopsides, chloroplast lipids, and epicuticular wax. Similar to other stress responses, DO-induced stress increased arabidopsides in an hour, but it was relatively minor for matured plants and reverted to the normal level in a few hours. The D-labeling isotopologue patterns of arabidopsides matched with those of galactolipid precursors, supporting the currently accepted biosynthesis mechanism. Matrix-assisted laser desorption/ionization (MALDI)-MSI was used to visualize the spatiotemporal distribution of deuterated chloroplast lipids, pheophytin , MGDGs, and DGDGs, after growing day-after-sowing (DAS) 28 plants in DO condition for 3-12 days. There was a gradual change of deuteration amount along the leaf tissues and with a longer labeling time, which was attributed to slow respiration leading to low DO concentration in the tissues. Finally, deuterium incorporation in epicuticular wax was visualized on the surfaces of the stem and flower. The conversion efficiency of newly synthesized C30 aldehyde to C29 ketone was very low in the lower stem but very high at the top of the stem near the flower or on the flower carpel. This study successfully demonstrated that MSI can unveil spatiotemporal metabolic activities in various tissues of .
PubMed: 38882571
DOI: 10.3389/fpls.2024.1379299 -
Science Advances Jun 2024Knowledge of the nucleosynthetic isotope composition of the outermost protoplanetary disk is critical to understand the formation and early dynamical evolution of the...
Knowledge of the nucleosynthetic isotope composition of the outermost protoplanetary disk is critical to understand the formation and early dynamical evolution of the Solar System. We report the discovery of outer disk material preserved in a pristine meteorite based on its chemical composition, organic-rich petrology, and N-rich, deuterium-rich, and O-poor isotope signatures. We infer that this outer disk material originated in the comet-forming region. The nucleosynthetic Fe, Mg, Si, and Cr compositions of this material reveal that, contrary to current belief, the isotope signature of the comet-forming region is ubiquitous among outer Solar System bodies, possibly reflecting an important planetary building block in the outer Solar System. This nucleosynthetic component represents fresh material added to the outer disk by late accretion streamers connected to the ambient molecular cloud. Our results show that most Solar System carbonaceous asteroids accreted material from the comet-forming region, a signature lacking in the terrestrial planet region.
PubMed: 38875339
DOI: 10.1126/sciadv.adp1613 -
Nature Communications Jun 2024Deuterium labeling compounds play a crucial role in organic and pharmaceutical chemistry. The synthesis of such compounds typically involves deuterated building blocks,...
Deuterium labeling compounds play a crucial role in organic and pharmaceutical chemistry. The synthesis of such compounds typically involves deuterated building blocks, allowing for the incorporation of deuterium atoms and functional groups into a target molecule in a single step. Unfortunately, the limited availability of synthetic approaches to deuterated synthons has impeded progress in this field. Here, we present an approach utilizing alkyl-substituted thianthrenium salts that efficiently and selectively introduce deuterium at the α position of alkyl chains through a pH-dependent HIE process, using DO as the deuterium source. The resulting α-deuterated alkyl thianthrenium salts, which bear two deuterium atoms, exhibit excellent selectivity and deuterium incorporation in electrophilic substitution reactions. Through in situ formation of isotopically labelled alkyl halides, these thianthrenium salts demonstrate excellent compatibility in a series of metallaphotoredox cross-electrophile coupling with (hetero)aryl, alkenyl, alkyl bromides, and other alkyl thianthrenium salts. Our technique allows for a wide range of substrates, high deuterium incorporation, and precise control over the site of deuterium insertion within a molecule such as the benzyl position, allylic position, or any alkyl chain in between, as well as neighboring heteroatoms. This makes it invaluable for synthesizing various deuterium-labeled compounds, especially those with pharmaceutical significance.
PubMed: 38871683
DOI: 10.1038/s41467-024-48590-w -
Molecular Cell Jun 2024Transcriptional coregulators and transcription factors (TFs) contain intrinsically disordered regions (IDRs) that are critical for their association and function in gene...
Transcriptional coregulators and transcription factors (TFs) contain intrinsically disordered regions (IDRs) that are critical for their association and function in gene regulation. More recently, IDRs have been shown to promote multivalent protein-protein interactions between coregulators and TFs to drive their association into condensates. By contrast, here we demonstrate how the IDR of the corepressor LSD1 excludes TF association, acting as a dynamic conformational switch that tunes repression of active cis-regulatory elements. Hydrogen-deuterium exchange shows that the LSD1 IDR interconverts between transient open and closed conformational states, the latter of which inhibits partitioning of the protein's structured domains with TF condensates. This autoinhibitory switch controls leukemic differentiation by modulating repression of active cis-regulatory elements bound by LSD1 and master hematopoietic TFs. Together, these studies unveil alternative mechanisms by which disordered regions and their dynamic crosstalk with structured regions can shape coregulator-TF interactions to control cis-regulatory landscapes and cell fate.
Topics: Histone Demethylases; Humans; Enhancer Elements, Genetic; Intrinsically Disordered Proteins; Transcription Factors; Animals; Protein Binding; Mice; Cell Differentiation; Gene Silencing
PubMed: 38870936
DOI: 10.1016/j.molcel.2024.05.017 -
Pharmacology Research & Perspectives Jun 2024According to the CDC, both Pfizer and Moderna COVID-19 vaccines contain nucleoside-modified messenger RNA (mRNA) encoding the viral spike glycoprotein of severe acute... (Review)
Review
According to the CDC, both Pfizer and Moderna COVID-19 vaccines contain nucleoside-modified messenger RNA (mRNA) encoding the viral spike glycoprotein of severe acute respiratory syndrome caused by corona virus (SARS-CoV-2), administered via intramuscular injections. Despite their worldwide use, very little is known about how nucleoside modifications in mRNA sequences affect their breakdown, transcription and protein synthesis. It was hoped that resident and circulating immune cells attracted to the injection site make copies of the spike protein while the injected mRNA degrades within a few days. It was also originally estimated that recombinant spike proteins generated by mRNA vaccines would persist in the body for a few weeks. In reality, clinical studies now report that modified SARS-CoV-2 mRNA routinely persist up to a month from injection and can be detected in cardiac and skeletal muscle at sites of inflammation and fibrosis, while the recombinant spike protein may persist a little over half a year in blood. Vaccination with 1-methylΨ (pseudouridine enriched) mRNA can elicit cellular immunity to peptide antigens produced by +1 ribosomal frameshifting in major histocompatibility complex-diverse people. The translation of 1-methylΨ mRNA using liquid chromatography tandem mass spectrometry identified nine peptides derived from the mRNA +1 frame. These products impact on off-target host T cell immunity that include increased production of new B cell antigens with far reaching clinical consequences. As an example, a highly significant increase in heart muscle 18-flourodeoxyglucose uptake was detected in vaccinated patients up to half a year (180 days). This review article focuses on medical biochemistry, proteomics and deutenomics principles that explain the persisting spike phenomenon in circulation with organ-related functional damage even in asymptomatic individuals. Proline and hydroxyproline residues emerge as prominent deuterium (heavy hydrogen) binding sites in structural proteins with robust isotopic stability that resists not only enzymatic breakdown, but virtually all (non)-enzymatic cleavage mechanisms known in chemistry.
Topics: Humans; COVID-19; COVID-19 Vaccines; mRNA Vaccines; Pseudouridine; Recombinant Proteins; RNA, Messenger; RNA, Viral; Spike Glycoprotein, Coronavirus; Vaccination; Vaccines, Synthetic
PubMed: 38867495
DOI: 10.1002/prp2.1218 -
Angewandte Chemie (International Ed. in... Jun 2024Isotopically labeled alkanes play a crucial role in organic and pharmaceutical chemistry. While some deuterated methylating agents are readily available, the limited...
Isotopically labeled alkanes play a crucial role in organic and pharmaceutical chemistry. While some deuterated methylating agents are readily available, the limited accessibility of other deuteroalkyl reagents has hindered the synthesis of corresponding products. In this study, we introduce a nickel-catalyzed system that facilitates the synthesis of various deuterium-labeled alkanes through the hydrodeuteroalkylation of d2-labeled alkyl TT salts with unactivated alkenes. Diverging from traditional deuterated alkyl reagents, alkyl thianthrenium (TT) salts can effectively and selectively introduce deuterium at α position of alkyl chains using D2O as the deuterium source via a single-step pH-dependent hydrogen isotope exchange (HIE). Our method allows for high deuterium incorporation, and offers precise control over the site of deuterium insertion within an alkyl chain. This technique proves to be invaluable for the synthesis of various deuterium-labeled compounds, especially those of pharmaceutical relevance.
PubMed: 38866703
DOI: 10.1002/anie.202409862 -
Protein Science : a Publication of the... Jul 2024Photoconvertible fluorescent proteins (pcFPs) undergo a slow photochemical transformation when irradiated with blue light. Since their emission is shifted from green to...
Photoconvertible fluorescent proteins (pcFPs) undergo a slow photochemical transformation when irradiated with blue light. Since their emission is shifted from green to red, pcFPs serve as convenient fusion tags in several cutting-edge biological imaging technologies. Here, a pcFP termed the Least Evolved Ancestor (LEA) was used as a model system to determine the rate-limiting step of photoconversion. Perdeuterated histidine residues were introduced by isotopic enrichment and chromophore content was monitored by absorbance. pH-dependent photoconversion experiments were carried out by exposure to 405-nm light followed by dark equilibration. The loss of green chromophore correlated well with the rise of red, and maximum photoconversion rates were observed at pH 6.5 (0.059 ± 0.001 min for red color acquisition). The loss of green and the rise of red provided deuterium kinetic isotope effects (DKIEs) that were identical within error, 2.9 ± 0.9 and 3.8 ± 0.6, respectively. These data indicate that there is one rate-determining step in the light reactions of photoconversion, and that CH bond cleavage occurs in the transition state of this step. We propose that these reactions are rate-limited on the min time scale by the abstraction of a proton at the His62 beta-carbon. A conformational intermediate such as a twisted or isomerized chromophore is proposed to slowly equilibrate in the dark to generate the red form. Additionally, His62 may shuttle protons to activate Glu211 to serve as a general base, while also facilitating beta-elimination. This idea is supported by a recent X-ray structure of methylated His62.
Topics: Kinetics; Luminescent Proteins; Green Fluorescent Proteins; Hydrogen-Ion Concentration; Photochemical Processes; Red Fluorescent Protein; Histidine; Deuterium; Light
PubMed: 38864740
DOI: 10.1002/pro.5069 -
Nature Communications Jun 2024Carboxylic acids are widely available and generally inexpensive from abundant biomass feedstocks, and they are suitable and generic coupling partners in synthetic...
Carboxylic acids are widely available and generally inexpensive from abundant biomass feedstocks, and they are suitable and generic coupling partners in synthetic chemistry. Reported herein is an electroreductive coupling of stable and versatile carboxylic acids with (hetero)arenes using protons as the hydrogen source. The application of an earth-abundant titanium catalyst has significantly improved the deoxygenative reduction process. Preliminary mechanistic studies provide insights into the deoxygenative reduction of in-situ generated ketone pathway, and the intermediacy generation of ketyl radical and alkylidene titanocene. Without the necessity of pressurized hydrogen or stoichiometric hydride as reductants, this protocol enables highly selective and straightforward synthesis of various functionalized and structurally diverse alkylbenzenes under mild conditions. The utility of this reaction is further demonstrated through practical and valuable isotope incorporation from readily available deuterium source.
PubMed: 38862567
DOI: 10.1038/s41467-024-49355-1 -
Chemistry (Weinheim An Der Bergstrasse,... Jun 2024The synthesis of a water-soluble, phosphine-pegylated iridium(I) catalyst and its application in hydrogen isotope exchange (HIE) reactions in buffer is reported. The...
The synthesis of a water-soluble, phosphine-pegylated iridium(I) catalyst and its application in hydrogen isotope exchange (HIE) reactions in buffer is reported. The longer polyethylene glycol side chains on the phosphine increased the water solubility independently from the pH. HIE reactions of polar substrates in protic solvents were studied. DFT calculations gave further insides into the catalytic processes. The scope and limitation of the pegylated catalyst was studied in HIE reactions of several complex compounds in borax buffer at pH 9 and the best conditions were applied in a tritium experiment with the drug telmisartan.
PubMed: 38861127
DOI: 10.1002/chem.202402038