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Communications Biology Apr 2024Cytosolic Ca and Na allosterically regulate Na/Ca exchanger (NCX) proteins to vary the NCX-mediated Ca entry/exit rates in diverse cell types. To resolve the...
Cytosolic Ca and Na allosterically regulate Na/Ca exchanger (NCX) proteins to vary the NCX-mediated Ca entry/exit rates in diverse cell types. To resolve the structure-based dynamic mechanisms underlying the ion-dependent allosteric regulation in mammalian NCXs, we analyze the apo, Ca, and Na-bound species of the brain NCX1.4 variant using hydrogen-deuterium exchange mass spectrometry (HDX-MS) and molecular dynamics (MD) simulations. Ca binding to the cytosolic regulatory domains (CBD1 and CBD2) rigidifies the intracellular regulatory loop (5L6) and promotes its interaction with the membrane domains. Either Na or Ca stabilizes the intracellular portions of transmembrane helices TM3, TM4, TM9, TM10, and their connecting loops (3L4 and 9L10), thereby exposing previously unappreciated regulatory sites. Ca or Na also rigidifies the palmitoylation domain (TMH2), and neighboring TM1/TM6 bundle, thereby uncovering a structural entity for modulating the ion transport rates. The present analysis provides new structure-dynamic clues underlying the regulatory diversity among tissue-specific NCX variants.
Topics: Animals; Protein Structure, Secondary; Mammals; Sodium-Calcium Exchanger
PubMed: 38627576
DOI: 10.1038/s42003-024-06159-9 -
Tree Physiology May 2024The oxygen and hydrogen isotopic composition (δ18O, δ2H) of plant tissues are key tools for the reconstruction of hydrological and plant physiological processes and...
The oxygen and hydrogen isotopic composition (δ18O, δ2H) of plant tissues are key tools for the reconstruction of hydrological and plant physiological processes and may therefore be used to disentangle the reasons for tree mortality. However, how both elements respond to soil drought conditions before death has rarely been investigated. To test this, we performed a greenhouse study and determined predisposing fertilization and lethal soil drought effects on δ18O and δ2H values of organic matter in leaves and tree rings of living and dead saplings of five European tree species. For mechanistic insights, we additionally measured isotopic (i.e. δ18O and δ2H values of leaf and twig water), physiological (i.e. leaf water potential and gas-exchange) and metabolic traits (i.e. leaf and stem non-structural carbohydrate concentration, carbon-to-nitrogen ratios). Across all species, lethal soil drought generally caused a homogenous 2H-enrichment in leaf and tree-ring organic matter, but a low and heterogenous δ18O response in the same tissues. Unlike δ18O values, δ2H values of tree-ring organic matter were correlated with those of leaf and twig water and with plant physiological traits across treatments and species. The 2H-enrichment in plant organic matter also went along with a decrease in stem starch concentrations under soil drought compared with well-watered conditions. In contrast, the predisposing fertilization had generally no significant effect on any tested isotopic, physiological and metabolic traits. We propose that the 2H-enrichment in the dead trees is related to (i) the plant water isotopic composition, (ii) metabolic processes shaping leaf non-structural carbohydrates, (iii) the use of carbon reserves for growth and (iv) species-specific physiological adjustments. The homogenous stress imprint on δ2H but not on δ18O suggests that the former could be used as a proxy to reconstruct soil droughts and underlying processes of tree mortality.
Topics: Plant Leaves; Droughts; Trees; Soil; Oxygen Isotopes; Water; Deuterium; Plant Stems
PubMed: 38618738
DOI: 10.1093/treephys/tpae043 -
American Journal of Veterinary Research Jun 2024The goal of this study was to characterize changes induced by a high-fat diet in body composition, insulin levels and sensitivity, blood lipids, and other key biomarkers...
OBJECTIVE
The goal of this study was to characterize changes induced by a high-fat diet in body composition, insulin levels and sensitivity, blood lipids, and other key biomarkers also associated with the metabolic dysfunction that occurs with natural aging.
ANIMALS
24 male Beagle dogs, 3 to 7 years of age, of mixed castration status.
METHODS
Dogs were randomly assigned to continue twice daily feeding of the commercial adult maintenance diet (n = 12, including 2 intact) that they were previously fed or to a high-fat diet (12, including 2 intact) for 17 weeks between December 1, 2021, and April 28, 2022. Assessments included body composition (weight, body condition score, and adipose mass determined by deuterium enrichment), clinical chemistries, plasma fatty acid quantification, oral glucose tolerance test, and histology of subcutaneous and visceral adipose biopsy samples.
RESULTS
The high-fat diet led to increased body weight, body condition score, fat mass and adipocyte size, hyperinsulinemia and peripheral insulin resistance, and elevations in serum lipids, including cholesterol, triglycerides, and several species of free fatty acids. Leptin levels increased in dogs fed a high-fat diet but not in control dogs. There were no significant changes in routine clinical chemistry values in either group.
CLINICAL RELEVANCE
Feeding a high-fat diet for 17 weeks led to potentially deleterious changes in metabolism similar to those seen in natural aging in dogs, including hyperinsulinemia, insulin resistance, and dyslipidemia. A high-fat diet model may provide insights into the similar metabolic dysfunction that occurs during natural aging.
Topics: Animals; Dogs; Male; Insulin Resistance; Diet, High-Fat; Hyperinsulinism; Dog Diseases; Dyslipidemias; Aging; Body Composition; Animal Feed; Random Allocation
PubMed: 38604223
DOI: 10.2460/ajvr.23.11.0253 -
Frontiers in Cellular Neuroscience 2024
PubMed: 38601024
DOI: 10.3389/fncel.2024.1401687 -
The Journal of Physical Chemistry. A Apr 2024While neutral reactions involved in methane oxidation have been intensively studied, much less information is known about the reaction dynamics of the oxygen radical...
While neutral reactions involved in methane oxidation have been intensively studied, much less information is known about the reaction dynamics of the oxygen radical anion with methane. Here, we study the scattering dynamics of this anion-molecule reaction using crossed-beam velocity map imaging with deuterated methane. Differential scattering cross sections for the deuterium abstraction channel have been determined at relative collision energies between 0.2 and 1.5 eV and ab initio calculations of the important stationary points along the reaction pathway have been performed. At lower collision energies, direct backscattering and indirect complex-mediated reaction dynamics are observed, whereas at higher energies, sideways deuterium stripping dominates the reaction. Above 0.7 eV collision energy, a suppressed cross section is observed at low product ion velocities, which is likely caused by the endoergic pathway of combined deuteron/deuterium transfer, forming heavy water. The measured product internal energy is attributed mainly to the low-lying deformation and out-of-plane bending vibrations of the methyl radical product. The results are compared with a previous crossed-beam result for the reaction of oxygen anions with nondeuterated ̧methane and with the related neutral-neutral reactions, showing similar dynamics and qualitative agreement.
PubMed: 38597714
DOI: 10.1021/acs.jpca.3c08274 -
Data in Brief Jun 2024This work presents the dataset of stable water isotopes of oxygen and hydrogen measured in water samples from different sources (precipitation, surface water,...
This work presents the dataset of stable water isotopes of oxygen and hydrogen measured in water samples from different sources (precipitation, surface water, groundwater, tap water) across Kazakhstan from 2017 to 2018 and from 2020 to 2023. The dataset includes results on isotopic composition of 399 water samples, namely precipitation: event-based ( = 108), cumulative monthly ( = 22); surface water: lakes, reservoirs, brooks, rivers, channels ( = 175), groundwater: shallow and artesian groundwater, spring ( = 85), tapwater ( = 9). For each sample name of the source, location, latitude, longitude and date of sampling, measurement uncertainty (one standard deviation) are available. The samples were assessed by plotting the data in dual δO vs. δH isotope space with reference to values found in the published literature and fitting a linear regression equation for Astana (event) precipitation. Overall, this is the first dataset covering wide range of sources across Kazakhstan, which could be used by global and regional water resource assessments and studies such as tracing water sources, hydrograph separation and end-member analyses, isotope mass balance, evapotranspiration partitioning, residence time analysis and groundwater recharge.
PubMed: 38590614
DOI: 10.1016/j.dib.2024.110360 -
Radiology. Imaging Cancer May 2024MR spectroscopy (MRS) is a noninvasive imaging method enabling chemical and molecular profiling of tissues in a localized, multiplexed, and nonionizing manner. As... (Review)
Review
MR spectroscopy (MRS) is a noninvasive imaging method enabling chemical and molecular profiling of tissues in a localized, multiplexed, and nonionizing manner. As metabolic reprogramming is a hallmark of cancer, MRS provides valuable metabolic and molecular information for cancer diagnosis, prognosis, treatment monitoring, and patient management. This review provides an update on the use of MRS for clinical cancer management. The first section includes an overview of the principles of MRS, current methods, and conventional metabolites of interest. The remainder of the review is focused on three key areas: advances in instrumentation, specifically ultrahigh-field-strength MRI scanners and hybrid systems; emerging methods for acquisition, including deuterium imaging, hyperpolarized carbon 13 MRI and MRS, chemical exchange saturation transfer, diffusion-weighted MRS, MR fingerprinting, and fast acquisition; and analysis aided by artificial intelligence. The review concludes with future recommendations to facilitate routine use of MRS in cancer management. MR Spectroscopy, Spectroscopic Imaging, Molecular Imaging in Oncology, Metabolic Reprogramming, Clinical Cancer Management © RSNA, 2024.
Topics: Humans; Artificial Intelligence; Magnetic Resonance Spectroscopy; Magnetic Resonance Imaging; Neoplasms
PubMed: 38578207
DOI: 10.1148/rycan.230101 -
Chemical Science Apr 2024A combined computational and experimental study reveals that -, - and -aminobiphenyl isomers undergo distinctly different photochemical reactions involving proton...
A combined computational and experimental study reveals that -, - and -aminobiphenyl isomers undergo distinctly different photochemical reactions involving proton transfer. Deuterium exchange experiments show that the -isomer undergoes a facile photoprotonation at a carbon atom excited-state intramolecular proton transfer (ESIPT). The -isomer undergoes water-assisted excited-state proton transfer (ESPT) and a photoredox reaction proton-coupled electron transfer (PCET). The -isomer undergoes a water-assisted ESPT reaction. All three reactions take place in the singlet excited-state, except for the photoredox process of the -isomer, which involves a triplet excited-state. Computations illustrate the important role of excited-state antiaromaticity relief in these photoreactions.
PubMed: 38577382
DOI: 10.1039/d4sc00642a -
RSC Chemical Biology Apr 2024Spectroscopic studies increasingly employ Raman tags exhibiting a signal in the cell - silent region of the Raman spectrum (1800-2800 cm), where bands arising from... (Review)
Review
Spectroscopic studies increasingly employ Raman tags exhibiting a signal in the cell - silent region of the Raman spectrum (1800-2800 cm), where bands arising from biological molecules are inherently absent. Raman tags bearing functional groups which contain a triple bond, such as alkyne and nitrile or a carbon-deuterium bond, have a distinct vibrational frequency in this region. Due to the lack of spectral background and cell-associated bands in the specific area, the implementation of those tags can help overcome the inherently poor signal-to-noise ratio and presence of overlapping Raman bands in measurements of biological samples. The cell - silent Raman tags allow for bioorthogonal imaging of biomolecules with improved chemical contrast and they have found application in analyte detection and monitoring, biomarker profiling and live cell imaging. This review focuses on the potential of the cell - silent Raman region, reporting on the tags employed for biomedical applications using variants of Raman spectroscopy.
PubMed: 38576725
DOI: 10.1039/d3cb00217a -
Nature Communications Apr 2024Deuterium/Tritium (D/T) handling in defined proportions are pivotal to maintain steady-state operation for fusion reactors. However, the hydrogen isotope effect in...
Deuterium/Tritium (D/T) handling in defined proportions are pivotal to maintain steady-state operation for fusion reactors. However, the hydrogen isotope effect in metal-hydrogen systems always disturbs precise D/T ratio control. Here, we reveal the dominance of kinetic isotope effect during desorption. To reconcile the thermodynamic stability and isotope effect, we demonstrate a quantitative indicator of T and further a local coordination design strategy that comprises thermodynamic destabilization with vibration enhancement of interstitial isotopes for isotope engineering. Based on theoretical screening analysis, an optimized Ti-Pd co-doped ZrTiCoPd alloy is designed and prepared. Compared to ZrCo alloy, the optimal alloy enables consistent isotope delivery together with a three-fold lower T, a five-fold lower energy barrier difference, a one-third lower isotopic composition deviation during desorption and an over two-fold higher cycling capacity. This work provides insights into the interaction between alloy and hydrogen isotopes, thus opening up feasible approaches to support high-performance fusion reactors.
PubMed: 38570487
DOI: 10.1038/s41467-024-47250-3