The major histocompatibility complex (MHC) class I-related molecule MHC-class-I-related protein 1 (MR1) presents metabolites to distinct MR1-restricted T cell subsets, including mucosal-associated invariant T (MAIT) and MR1T cells. However, self-reactive MR1T cells and the nature of recognized antigens remain underexplored. Here, we report a cell endogenous carbonyl adduct of adenine (8-(9H-purin-6-yl)-2-oxa-8-azabicyclo[3.
View Article and Find Full Text PDFBackground: Heart-Smile Training (HST) is an interoceptive compassion-based behavioral intervention that in case reports has been beneficial for depression. Interoception refers to the awareness and regulation of physiological signals from inside the body. Depressed patients often have diminished interoceptive awareness and often experience disconnection from bodily needs and sensations.
View Article and Find Full Text PDFBackground: Adverse Childhood Experience (ACE) has detrimental impacts on neural development, especially hippocampal morphometry. Mindfulness-Based Interventions (MBI) has been shown to induce adaptive hippocampal changes especially at the subiculum. The present study aims to investigate the effects of MBI on subiculum volumes among ACE survivors, as well as the effects on episodic memory as a probe into hippocampal functionality.
View Article and Find Full Text PDFMR1T cells are a recently found class of T cells that recognize antigens presented by the major histocompatibility complex-I-related molecule MR1 in the absence of microbial infection. The nature of the self-antigens that stimulate MR1T cells remains unclear, hampering our understanding of their physiological role and therapeutic potential. By combining genetic, pharmacological, and biochemical approaches, we found that carbonyl stress and changes in nucleobase metabolism in target cells promote MR1T cell activation.
View Article and Find Full Text PDFBackground: Adverse Childhood Experience (ACE) has been shown to have detrimental impact on amygdala structure. Prior research found that adaptive psychological changes after Mindfulness-Based Interventions (MBI) were associated with amygdala volumetric changes. The present study aims to further investigate whether such effects also occur among ACE survivors and whether the effects are unique to MBI.
View Article and Find Full Text PDFThe changes in mean-squared charge radii of neutron-deficient gold nuclei have been determined using the in-source, resonance-ionization laser spectroscopy technique, at the ISOLDE facility (CERN). From these new data, nuclear deformations are inferred, revealing a competition between deformed and spherical configurations. The isotopes ^{180,181,182}Au are observed to possess well-deformed ground states and, when moving to lighter masses, a sudden transition to near-spherical shapes is seen in the extremely neutron-deficient nuclides, ^{176,177,179}Au.
View Article and Find Full Text PDFUsing the fusion-evaporation reaction ^{96}Ru(^{58}Ni,p4n)^{149}Lu and the MARA vacuum-mode recoil separator, a new proton-emitting isotope ^{149}Lu has been identified. The measured decay Q value of 1920(20) keV is the highest measured for a ground-state proton decay, and it naturally leads to the shortest directly measured half-life of 450_{-100}^{+170} ns for a ground-state proton emitter. The decay rate is consistent with l_{p}=5 emission, suggesting a dominant πh_{11/2} component for the wave function of the proton-emitting state.
View Article and Find Full Text PDFParamagnetic centers in biomolecules, such as specific metal ions that are bound to a protein, affect the nuclei in their surrounding in various ways. One of these effects is the pseudocontact shift (PCS), which leads to strong chemical shift perturbations of nuclear spins, with a remarkably long range of 50 Å and beyond. The PCS in solution NMR is an effect originating from the anisotropic part of the dipole-dipole interaction between the magnetic momentum of unpaired electrons and nuclear spins.
View Article and Find Full Text PDFCurr Treat Options Psychiatry
June 2021
Purpose Of Review: Survivors of childhood maltreatment are at high risk for developing complex psychiatric disorders. Traditional treatments, including psychopharmacology, tend to be less efficacious for this population. This scoping review aimed to discuss existing empirical studies on the effects of mindfulness-based interventions for adult childhood trauma survivors, as well as the documented clinical challenges and adaptations for this population.
View Article and Find Full Text PDFThe amygdala morphometry is highly sensitive to stress and is implicated in various psychopathologies that are common among individuals with childhood maltreatment histories. This pilot study investigated bilateral amygdala volumetric changes among 15 young adults with childhood maltreatment histories undergoing an eight-week mindfulness intervention compared to 19 matched participants in a waitlist control group. Results indicated significant cross-individual variability in amygdala volumetric changes after the intervention, which resulted in no significant group by time interaction effect.
View Article and Find Full Text PDFAn amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFHerein, a novel and rationally designed ortho-substituted pyridine activator is reported that reacts rapidly and selectively with cysteine thiols. It forms reduction-stable conjugates and induces large pseudocontact shifts, residual dipolar couplings and paramagnetic relaxation enhancement on both ubiquitin S57C and human carbonic anhydrase II S50C constructs under physiological conditions.
View Article and Find Full Text PDFChildhood maltreatment has long lasting impacts on neural development of the hippocampus, which is important for learning and memory. The present study aimed to assess the effects of a mindfulness based intervention on hippocampal morphometry and episodic memory in this population. We administered MRI, psychological questionnaires and an episodic memory task to 21 participants (5 males) before and after a mindfulness-based behavioral intervention, compared to 21 participants (7 males) on the waiting list.
View Article and Find Full Text PDFObjectives: Individuals with a childhood maltreatment history tend to have various psychological symptoms and impaired social functioning. This study aimed to investigate the related therapeutic effects of a mindfulness-based intervention in this population.
Methods: We analyzed self-report questionnaire scores of the Mindful Attention Awareness Scale (MAAS), Non-Attachment Scale (NAS), Adult Rejection Sensitivity Questionnaire (A-RSQ), Interpersonal Reactivity Index (IRI), PTSD CheckList (PCL), and Anxiety Sensitivity Index (ASI), from 16 (3 males) young adults (age range 22-29) with mild to moderate childhood maltreatment, compared to 18 matched participants (6 males) on a waiting list, during both pre- and post-intervention/waiting periods.
There is sparse direct experimental evidence that atomic nuclei can exhibit stable "pear" shapes arising from strong octupole correlations. In order to investigate the nature of octupole collectivity in radium isotopes, electric octupole (E3) matrix elements have been determined for transitions in ^{222,228}Ra nuclei using the method of sub-barrier, multistep Coulomb excitation. Beams of the radioactive radium isotopes were provided by the HIE-ISOLDE facility at CERN.
View Article and Find Full Text PDFProg Nucl Magn Reson Spectrosc
June 2020
In this review, lanthanide chelating tags and their applications to pseudocontact shift NMR spectroscopy as well as analysis of residual dipolar couplings are covered. A complete overview is presented of DOTA-derived and non-DOTA-derived lanthanide chelating tags, critical points in the design of lanthanide chelating tags as appropriate linker moieties, their stability under reductive conditions, e.g.
View Article and Find Full Text PDFBackground: Individuals who were maltreated during childhood are faced with increased risks for developing various psychological symptoms that are particularly resistant to traditional treatments. This pilot study investigated the effects of a mindfulness based behavioral intervention for young adults with a childhood maltreatment history.
Methods: This study looked at self-report psychological questionnaires from 20 subjects (5 males) before and after a mindfulness-based behavioral intervention, compared to 18 subjects (6 males) in the waiting list control group (age range 22-29); all subjects experienced mild-to-moderate childhood maltreatment.
The formylglycine generating enzyme (FGE) catalyzes oxidative conversion of specific peptidyl-cysteine residues to formylglycine. FGE mediates O-activation and hydrogen-atom abstraction in an active site that contains Cu(i) coordinated to two cysteine residues. Similar coordination geometries are common among copper-sensing transcription factors and copper-chaperone but are unprecedented among copper-dependent oxidases.
View Article and Find Full Text PDFHerein we report a DOTA-based lanthanide chelating tag (LCT) with rigidified backbone and a reduction-stable linker. The newly developed tag induces strong pseudocontact shifts suitable for paramagnetic protein nuclear magnetic resonance spectroscopy and the obtained anisotropic susceptibility parameters are in the range of the best performing LCTs.
View Article and Find Full Text PDFA sterically overcrowded lanthanide-chelating tag has been synthesized in order to investigate the influence on the obtained pseudocontact shifts and the anisotropic part of the magnetic susceptibility tensor compared to those of its predecessor DOTA-M8-(4R,4S)-SSPy. For the first time, a concise synthetic route is presented for isopropyl-substituted cyclen, the macrocyclic scaffold of the lanthanide-chelating tag, delivering the macrocycle in an overall yield of 6 % over 11 steps. The geometry of the lutetium complex has been assigned by ROESY experiments, adopting exclusively a Λ(δδδδ) conformation, and DFT calculations have confirmed a stabilization of 32.
View Article and Find Full Text PDFUnraveling the native structure of protein-ligand complexes in solution enables rational drug design. We report here the use of F pseudocontact shift (PCS) NMR as a method to determine fluorine positions of high affinity ligands bound within the drug target human carbonic anhydrase II with high accuracy. Three different ligands were localized within the protein by analysis of the obtained PCS from simple one-dimensional F spectra with an accuracy of up to 0.
View Article and Find Full Text PDFA rational strategy for the facile and efficient cyclization of amino acid-based linear precursors forming nine and twelve-membered cyclic peptidomimetics is reported. The resulting chiral lactams can readily be reduced to substituted cyclic polyamine analogues of 1,4,7,10-tetraaza-cyclododecane (cyclen) and 1,4,7-triaza-cyclononane (TACN).
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