Magnetic Resonance Investigation Research Articles

Nuclear magnetic resonance investigation of superconducting and normal state Nb3Sn

The superconductor Nb3Sn has important applications for construction of very high-field superconducting magnets. In this work we investigate its microscopic electronic structure with 93Nb nuclear magnetic resonance (NMR). The high-quality Nb3Sn powder sample was studied in both 3.2 T and 7 T magnetic fields in the temperature range from 4 K to 300 K. From measurement of the spectrum and its theoretical analysis, we find evidence for anisotropy despite its cubic crystal structure. Magnetic alignment of the powder grains in the superconducting state was also observed. The Knight shift and spin-lattice relaxation rate, T1−1 , were measured and the latter compared with BCS theory for the energy gap Δ(0)=2.7±0.3kBTc at 3.2 T and Δ(0)=2.33±0.07kBTc at 7 T, indicating suppression of the order parameter by magnetic field.

Simultaneous Positron Emission Tomography and Molecular Magnetic Resonance Imaging of Cardiopulmonary Fibrosis in a Mouse Model of Left Ventricular Dysfunction.

Aging-associated left ventricular dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)-magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in a left ventricular dysfunction model. Left ventricular dysfunction was induced by transverse aortic constriction (TAC) in 6-month-old senescence-accelerated prone mice, a subset of mice that received sham surgery. Three weeks after surgery, mice underwent simultaneous PET-MRI at 4.7 T. Collagen-targeted PET and fibrogenesis magnetic resonance (MR) probes were intravenously administered. PET signal was computed as myocardium- or lung-to-muscle ratio. Percent signal intensity increase and Δ lung-to-muscle ratio were computed from the pre-/postinjection magnetic resonance images. Elevated allysine in the heart (P=0.02) and lungs (P=0.17) of TAC mice corresponded to an increase in myocardial magnetic resonance imaging percent signal intensity increase (P<0.0001) and Δlung-to-muscle ratio (P<0.0001). Hydroxyproline in the heart (P<0.0001) and lungs (P<0.01) were elevated in TAC mice, which corresponded to an increase in heart (myocardium-to-muscle ratio, P=0.02) and lung (lung-to-muscle ratio, P<0.001) PET measurements. Pressure-volume loop and echocardiography demonstrated adverse left ventricular remodeling, function, and increased right ventricular systolic pressure in TAC mice. Administration of collagen-targeted PET and allysine-targeted MR probes led to elevated PET-magnetic resonance imaging signals in the myocardium and lungs of TAC mice. The study demonstrates the potential to detect fibrosis and fibrogenesis in cardiopulmonary disease through a dual molecular PET-magnetic resonance imaging protocol.

A Chromium-Based magnetic resonance probe for in situ gastric pH imaging

Effective monitoring of gastric fluid pH is crucial for diagnosing gastric diseases and evaluating anti-gastric-acid therapies. The invasiveness and low patient compliance with traditional gastric fluid aspiration methods highlight the need of a non-invasive, real-time technique for in situ gastric pH monitoring. This study introduces a novel chromium (Cr)-based magnetic resonance probe, Cr(OH)3@HSA, specifically designed for pH-sensitive gastric imaging. Synthesized via an albumin-mediated biomimetic mineralization process, Cr(OH)3@HSA possesses an amorphous structure that facilitates the sensitive release of paramagnetic Cr(III) ions in acidic environments. This release substantially decreases the longitudinal relaxation time of surrounding hydrogen protons, as demonstrated by an 18.29-fold increase in the longitudinal relaxation rate from pH 6.5 to pH 1.0. In vivo experiments show that Cr(OH)3@HSA accurately detects abnormal gastric pH levels and evaluates the efficacy of gastric antiacids, surpassing the performance of the conventional “always-on” contrast agent, Magnevist®. Notably, our research reveals that chromium picolinate, a common dietary supplement for diabetes, generates a “turn-on” signal in the gastrointestinal tract, suggesting potential MR signal interference in diabetic patients. Consequently, we recommend that diabetic patients avoid chromium-based dietary supplements prior to MRI procedures to prevent Cr(III)-induced signal alterations.

A chiral fluorescent probe for molecular recognition of basic amino acids in solutions and cells

A novel and readily available binaphthyl-based fluorescent probe (S)-1 was designed and synthesized. (S)-1 can be used to not only chemoselectively discriminate 3 basic amino acids out of common amino acids, but also enantioselectively recognize histidine. Encouragingly, enantioselective imaging of histidine in cells was achieved for the first time by the probe (S)-1. These performances endowed it potential application in the chiral analysis of basic amino acids in asymmetric synthesis and cell imaging for diagnosis of diseases caused by racemization of histidine. Nuclear magnetic resonance (NMR) and mass spectrometry investigations suggested that different reaction extent of (S)-1 with l/d-histidine and different product structures generated the observed enantioselective fluorescent response. The molecular structures and thermodynamic stability of the complexes, formed from (S)-1 + Zn2+ and enantiomers of histidine, were calculated by Gaussian 16 based on density functional theory (DFT) to validate the above action mechanism.

Noncontact In Situ Multidiagnostic NMR/Dielectric Spectroscopy.

Introduction of a dielectric material in a nuclear magnetic resonance (NMR) probe head modifies the frequency response of the probe circuit, a phenomenon revealed by detuning of the probe. For NMR spectroscopy, this detuning is corrected for by tuning and matching the probe head prior to the NMR measurement. The magnitude of the probe detuning, "the dielectric shift", provides direct access to the dielectric properties of the sample, enabling NMR spectrometers to simultaneously perform both dielectric and NMR spectroscopy. By measuring sample dielectric permittivity as a function of frequency, dielectric permittivity spectroscopy can be performed using the new methodology. As a proof of concept, this was evaluated on methanol, ethanol, 1-propanol, 1-pentanol, and 1-octanol using a commercial cross-polarization magic angle spinning (CPMAS) NMR probe head. The results accurately match the literature data collected by standard dielectric spectroscopy techniques. Subsequently, the method was also applied to investigate the solvent-surface interactions of water confined in the micropores of an MFI-type, hydrophilic zeolite with a Si/Al ratio of 11.5. In the micropores, water adsorbs to Bro̷nsted acid sites and defect sites, resulting in a drastically decreased dielectric permittivity of the nanoconfined water. Theoretical background for the new methodology is provided using an effective electric circuit model of a CPMAS probe head with a solenoid coil, describing the detuning resulting from the insertion of dielectric samples in the probe head.

Large dynamics of a phase separating arginine-glycine-rich domain revealed via nuclear and electron spins

Liquid-liquid phase separation is the key process underlying formation of membrane-less compartments in cells. A highly dynamic cellular body with rapid component exchange is Cajal body (CB), which supports the extensive compositional dynamics of the RNA splicing machinery, spliceosome. Here, we select an arginine-glycine (RG)-rich segment of coilin, the major component of CB, establish its RNA-induced phase separation, and through combined use of nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) probes, interrogate its dynamics within the crowded interior of formed droplets. Taking advantage of glycine-based singlet-states, we show that glycines retain a large level of sub-nanoseconds dynamics inside the coilin droplets. Furthermore, the continuous-wave (CW) and electron-electron dipolar (PELDOR) and electron-nucleus hyperfine coupling EPR data (HYSCORE) support the RNA-induced formation of dynamic coilin droplets with high coilin peptide concentrations. The combined NMR and EPR data reveal the high dynamics of the RG-rich coilin within droplets and suggest its potential role in the large dynamics of CBs.

Designing surface exposed sites on Bacillus subtilis lipase A for spin-labeling and hydration studies

Spin-labeling with electron paramagnetic resonance spectroscopy (EPR) is a facile method for interrogating macromolecular flexibility, conformational changes, accessibility, and hydration. Within we present a computationally based approach for the rational selection of reporter sites in Bacillus subtilis lipase A (BSLA) for substitution to cysteine residues with subsequent modification with a spin-label that are expected to not significantly perturb the wild-type structure, dynamics, or enzymatic function. Experimental circular dichroism spectroscopy, Michaelis-Menten kinetic parameters and EPR spectroscopy data validate the success of this approach to computationally select reporter sites for future magnetic resonance investigations of hydration and hydration changes induced by polymer conjugation, tethering, immobilization, or amino acid substitution in BSLA. Analysis of molecular dynamic simulations of the impact of substitutions on the secondary structure agree well with experimental findings. We propose that this computationally guided approach for choosing spin-labeled EPR reporter sites, which evaluates relative surface accessibility coupled with hydrogen bonding occupancy of amino acids to the catalytic pocket via atomistic simulations, should be readily transferable to other macromolecular systems of interest including selecting sites for paramagnetic relaxation enhancement NMR studies, other spin-labeling EPR studies or any method requiring a tagging method where it is desirable to not alter enzyme stability or activity.

Fractal and Multifractal Characteristics on Pore Structure of Coal-Based Sedimentary Rocks Using Nuclear Magnetic Resonance

Summary Unconventional reservoirs have nanoscale pores, complex pore structures, and heterogeneity that directly affect reservoir storage performance and fluid transport capacity. In this study, shale, mudstone, and sandstone, three typical coal sedimentary rocks from the Daqiang coal mine in the Tifa Basin, were selected for nuclear magnetic resonance (NMR) and scanning electron microscopy (SEM) investigation, with the aim to investigate the pore structure and multifractal characteristics of the coal sedimentary reservoirs and to qualitatively analyze the effects of the physical property parameters and the mineralogical compositions on the multifractal parameters. The distribution data of the NMR T2 spectra were analyzed. The results showed that (1) SEM analysis concluded that the pore system of the three different lithological samples (mudstone, shale, and sandstone) was dominated by mineral matrix pores (i.e., intergranular and intragranular pores) and in the sandstone samples, there were only a few biological pores found. (2) The distribution of the NMR T2 spectrum peaks indicates that the sandstone and shale T2 spectra are bimodal, dominated by micropores, and contain a small number of transitional pores; most of the T2 spectra of mudstone are single peaks in distribution, mainly dominated by micropores. (3) Multifractal parameters are positively correlated with porosity and significantly negatively correlated with permeability; multifractal parameters are significantly positively correlated with the content of clay minerals and kaolinite, which suggests that the increase in clay minerals and kaolinite content enhances the heterogeneity of the pore space. The negative correlation with the content of quartz suggests that the enrichment of quartz reduces the irregularity of the pore space.

Recent progress on MRI probes for metal ion detection and biological applications

The disorder of metal ion levels can have a significant impact on the ecological environment and human health due to their crucial role in complex biological metabolism processes and the overall ecological balance. Multiple magnetic resonance probes are used for detecting these metal ions.

Molecular Control of Triplet-Pair Spin Polarization and Its Optoelectronic Magnetic Resonance Probes.

ConspectusPreparing and manipulating pure magnetic states in molecular systems are the key initial requirements for harnessing the power of synthetic chemistry to drive practical quantum sensing and computing technologies. One route for achieving the requisite higher spin states in organic systems exploits the phenomenon of singlet fission, which produces pairs of triplet excited states from initially photoexcited singlets in molecular assemblies with multiple chromophores. The resulting spin states are characterized by total spin (quintet, triplet, or singlet) and its projection onto a specified molecular or magnetic field axis. These excited states are typically highly polarized but exhibit an impure spin population pattern. Herein, we report the prediction and experimental verification of molecular design rules that drive the population of a single pure magnetic state and describe the progress toward its experimental realization.A vital feature of this work is the close partnership among theory, chemical synthesis, and spectroscopy. We begin by presenting our theoretical framework for understanding spin manifold interconversion in singlet fission systems. This theory makes specific testable predictions about the intermolecular structure and orientation relative to an external magnetic field that should lead to pure magnetic state preparation and provides a powerful tool for interpreting magnetic spectra. We then test these predictions through detailed magnetic spectroscopy experiments on a series of new molecular architectures that meet one or more of the identified structural criteria. Many of these architectures rely on the synthesis of molecules with features unique to this effort: rigid bridges between chromophores in dimers, heteroacenes with tailored singlet/triplet-pair energy level matching, or side-group engineering to produce specific crystal structures. The spin evolution of these systems is revealed through our application and development of several magnetic resonance methods, each of which has different sensitivities and relevance in environments relevant to quantum applications.Our theoretical predictions prove to be remarkably consistent with our experimental results, though experimentally meeting all the structural prescriptions demanded by theory for true pure-state preparation remains a challenge. Our magnetic spectra agree with our model of triplet-pair behavior, including funneling of the population to the ms = 0 magnetic sublevel of the quintet under specified conditions in dimers and crystals, showing that this phenomenon is subject to control through molecular design. Moreover, our demonstration of novel and/or highly sensitive detection mechanisms of spin states in singlet fission systems, including photoluminescence (PL), photoinduced absorption (PA), and magnetoconductance (MC), points the way toward both a deeper understanding of how these systems evolve and technologically feasible routes toward experiments at the single-molecule quantum limit that are desirable for computational applications.

Magnetic resonance investigation of conformational responses of tau protein to specific phosphorylation

Intrinsically disordered proteins (IDPs) are known to adopt many rapidly interconverting structures, making it difficult to pinpoint the specific conformational states that are relevant for their function. Tau is an important IDP, and its conformation is known to be affected by post-translational modifications (PTMs), such as phosphorylation. To investigate the effect of specific phosphorylation on full-length Tau's dynamic global conformation, we employed a combination of nuclear magnetic resonance-based paramagnetic relaxation interference methods and electron paramagnetic resonance spectroscopy. By reproducing the AT8 epitope, comprising exclusive phosphorylation at residues S202 and T205, we were able to identify conformations specific to phosphorylated Tau, which exhibited a tendency towards less compact states. These mechanistic details are of significance to understand the path leading from soluble Tau to the ordered structure of Tau fibers. This approach proved to be successful for studying the conformational changes of (phosphorylated) full-length Tau and can potentially be extended to the study of other IDPs that undergo various PTMs.

Neurobiological mechanisms of ECT and TMS treatment in depression: study protocol of a multimodal magnetic resonance investigation

BackgroundNoninvasive neurostimulation treatments are increasingly being used to treat major depression, which is a common cause of disability worldwide. While electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) are both effective in treating depressive episodes, their mechanisms of action are, however, not completely understood. ECT is given under general anesthesia, where an electrical pulse is administered through electrodes placed on the patient’s head to trigger a seizure. ECT is used for the most severe cases of depression and is usually not prescribed before other options have failed. With TMS, brain stimulation is achieved through rapidly changing magnetic fields that induce electric currents underneath a ferromagnetic coil. Its efficacy in depressive episodes has been well documented. This project aims to identify the neurobiological underpinnings of both the effects and side effects of the neurostimulation techniques ECT and TMS.MethodsThe study will utilize a pre-post case control longitudinal design. The sample will consist of 150 subjects: 100 patients (bipolar and major depressive disorder) who are treated with either ECT (N = 50) or TMS (N = 50) and matched healthy controls (N = 50) not receiving any treatment. All participants will undergo multimodal magnetic resonance imaging (MRI) as well as neuropsychological and clinical assessments at multiple time points before, during and after treatment. Arterial spin labeling MRI at baseline will be used to test whether brain perfusion can predict outcomes. Signs of brain disruption, potentiation and rewiring will be explored with resting-state functional MRI, magnetic resonance spectroscopy and multishell diffusion weighted imaging (DWI). Clinical outcome will be measured by clinician assessed and patient reported outcome measures. Memory-related side effects will be investigated, and specific tests of spatial navigation to test hippocampal function will be administered both before and after treatment. Blood samples will be stored in a biobank for future analyses. The observation time is 6 months. Data will be explored in light of the recently proposed disrupt, potentiate and rewire (DPR) hypothesis.DiscussionThe study will contribute data and novel analyses important for our understanding of neurostimulation as well as for the development of enhanced and more personalized treatment.Trial registrationClinicalTrials.gov Identifier: NCT05135897.

Quantitative Magnetic Resonance Imaging to Assess Progression and Rupture Risk of Aortic Aneurysms: A Scoping Review.

In current practice, the diameter of an aortic aneurysm is utilized to estimate the rupture risk and decide upon timing of elective repair, although it is known to be imprecise and not patient-specific. Quantitative magnetic resonance imaging (MRI) enables the visualization of several biomarkers that provide information about processes within the aneurysm and may therefore facilitate patient-specific risk stratification. We performed a scoping review of the literature on quantitative MRI techniques to assess aortic aneurysm progression and rupture risk, summarized these findings, and identified knowledge gaps. Literature concerning primary research was of interest and the medical databases PubMed, Scopus, Embase, and Cochrane were systematically searched. This study used the PRISMA protocol extension for scoping reviews. Articles published between January 2010 and February 2023 involving animals and/or humans were included. Data were extracted by 2 authors using a predefined charting method. A total of 1641 articles were identified, of which 21 were included in the scoping review. Quantitative MRI-derived biomarkers were categorized into hemodynamic (8 studies), wall (5 studies) and molecular biomarkers (8 studies). Fifteen studies included patients and/or healthy human subjects. Animal models were investigated in the other 6 studies. A cross-sectional study design was the most common, whereas 5 animal studies had a longitudinal component and 2 studies including patients had a prospective design. A promising hemodynamic biomarker is wall shear stress (WSS), which is estimated based on 4D-flow MRI. Molecular biomarkers enable the assessment of inflammatory and wall deterioration processes. The ADAMTS4-specific molecular magnetic resonance (MR) probe showed potential to predict abdominal aortic aneurysm (AAA) formation and rupture in a murine model. Wall biomarkers assessed using dynamic contrast-enhanced (DCE) MRI showed great potential for assessing AAA progression independent of the maximum diameter. This scoping review provides an overview of quantitative MRI techniques studied and the biomarkers derived from them to assess aortic aneurysm progression and rupture risk. Longitudinal studies are needed to validate the causal relationships between the identified biomarkers and aneurysm growth, rupture, or repair. In the future, quantitative MRI could play an important role in the personalized risk assessment of aortic aneurysm rupture. The currently used maximum aneurysm diameter fails to accurately assess the multifactorial pathology of an aortic aneurysm and precisely predicts rupture in a patient-specific manner. Quantitative magnetic resonance imaging (MRI) enables the detection of various quantitative parameters involved in aneurysm progression and subsequent rupture. This scoping review provides an overview of the studied quantitative MRI techniques, the biomarkers derived from them, and recommendations for future research needed for the implementation of these biomarkers. Ultimately, quantitative MRI could facilitate personalized risk assessment for patients with aortic aneurysms, thereby reducing untimely repairs and improving rupture prevention.

Role of imperfect coordination of amorphous metal oxide in its chemical reaction with epoxy resin in metal − polymer hybrid material

The chemical bonding between laser − induced metal oxide and polymer highly determines the interfacial bonding performance of metal − polymer hybrid materials. To achieve reliable interfacial chemical bonding, it is crucial to gain a molecular/atomic level understanding of the chemical reaction mechanism between the metal oxide and epoxy resin (main components of epoxy polymer). Previous research has demonstrated that laser ablation induces the formation of amorphous aluminium oxide on aluminium alloy surfaces. Our solid − state nuclear magnetic resonance (ssNMR) investigation reveals that this amorphous aluminium oxide is consisted mainly of 4 − fold and 5 − fold coordinated Al sites. Through an innovative combination of ssNMR and density functional theory calculations, this aluminium oxide was confirmed to form Al − O − C bonds with epoxy resin, preferentially at imperfectly coordinated Al sites due to active donor − acceptor interactions. It is clarified that imperfect coordination of amorphous aluminium oxide plays a more critical role than its amorphous nature in forming stable adsorption structure with epoxy resin. Furthermore, compared to on crystalline surface, 5 − fold coordinated Al site on amorphous surface exhibits higher reactivity, and the origin of activity is revealed through distortion/interaction analysis. This study provides a research guidance for further regulation and optimization of interfacial reactivity and bonding characteristics of metal − polymer hybrid materials.

Low-Field Nuclear Magnetic Resonance Investigation on Early Hydration Characterization of Cement Paste Mixed with Mineral Admixtures

Mineral admixtures (MA), like fly ash (FA), silica fume (SF), and slag (S), are usually added to cement-based materials to improve their compactness and further enhance their mechanical properties, permeability resistance, and durability. In this study, low-field nuclear magnetic resonance (LF-NMR) is adopted to explore the evolution of the early hydration characterization of cement-based materials with MA by testing the transverse relaxation time T2. Meanwhile, the effect of MA on mechanical properties is analyzed by measuring compressive and flexural strength. The results show that, in the early hydration (0–7 days), the T2 distribution shows a trend of gradually moving to a short relaxation time and changes from a double peak to a single main peak. The decrease in T2i (main peak vertex) means that the evaporated water is gradually distributed in smaller pores with more motion constraints. However, the type and content of MA have little effect on T2i. Porosity gradually decreases in the period of early hydration. The addition of MA causes the porosity to decrease, and the order influence is FA &gt; S &gt; SF, i.e., the porosities of cement paste with 0%MA, 10%FA + 10%SF, 10%FA + 10%S, and 20%FA at 7 days are 48%, 44.5%, 40.7%, and 40.2%, respectively. Additionally, the addition of MA to cement-based materials also decreases the early strength, and the influence order is FA &gt; S &gt; SF, i.e., the compression strength values of cement paste with 0%MA, 10%FA + 10%SF, 10%FA + 10%S, and 20%FA at 7 days are 47.8 MPa, 40.1 MPa, 38.6 MPa, and 37 MPa, respectively.

Atomic Layer Deposition of the Geometry Separated Lewis and Brønsted Acid Sites for Cascade Glucose Conversion.

Solid acid catalysts with bi-acidity are promising as workhouse catalysts in biorefining to produce high-quality chemicals and fuels. Herein, we report a new strategy to develop bi-acidic cascade catalysts by separating both acid sites in geometry via the atomic layer deposition (ALD) of Lewis acidic alumina on Brønsted acidic supports. Visualized by transmission electron microscopy and electron energy loss spectroscopy mapping, the ALD-deposited alumina forms a conformal alumina domain with a thickness of around 3 nm on the outermost surface of mesoporous silica-alumina. Solid state nuclear magnetic resonance investigation shows that the dominant Lewis acid sites distribute on the outermost surface, whereas intrinsic Brønsted acid sites locate inside the nanopores within the silica-rich substrate. In comparison to other bi-acidic solid catalyst counterparts, the special geometric distance of Lewis and Brønsted acid sites minimized the synergetic effect, leading to a cascade reaction environment. For cascade glucose conversion, the designed ALD catalyst showed a highly enhanced catalytic performance.

(Invited) Investigating Polymorphism in Na2Fe2F7 and Its Effect on Electrochemical Properties

With the present materials supply crunch caused by the burgeoning Li-ion battery-based electric vehicle market, more sustainable battery chemistries are needed. When considering possible chemistries, sodium (Na) and iron (Fe) stand out as promising candidates for the intercalant ions and redox centers, respectively. Recently, weberite-type sodium metal fluorides (Na2 M 2+ Mʹ 3+F7) have emerged as potential high performance Na cathode materials1-4 with predicted energy densities in the 600 to 800 Wh/kg range (higher than any known Na cathode material) and high ionic conductivity and structural stability. One of the few weberites that has been electrochemically tested so far is Na2Fe2F7 and while one study has shown it to have great, high-rate performance,2 there have been inconsistent reports regarding the structure and electrochemical properties of Na2Fe2F7.In this study, we endeavor to reconcile these characteristics using a combined experimental-computational approach. Density functional theory calculations reveal the inherent metastability of the weberite phase and the close energetics of several Na2Fe2F7 polymorphic forms, as well as the predicted (de)intercalation behavior for each Na2Fe2F7 polymorph. Experimentally, we find that Na2Fe2F7 samples inevitably contain a mixture of weberite polymorphs as characterized using a broad suite of long-range and local probes sensitive to both amorphous and crystalline phases. Notably, we present the first ever 23Na nuclear magnetic resonance (NMR) investigation into weberites and showcase NMR’s ability to parse out different local environments despite the presence of polymorphism. Electrochemically, our Na2Fe2F7 material shows respectable early capacities yet exhibits steady capacity fade, which ex situ synchrotron X-ray diffraction and 23Na NMR reveal to be associated with transformation of the weberite phase upon cycling. However, fine tuning of electrode composition and design appears to be effective at reducing this effect.Overall, this study presents an in-depth characterization of Na2Fe2F7 and provides key insights that pave the way to unlocking weberites as high energy density Na-ion cathode materials.This work made use of the shared facilities of the UC Santa Barbara MRSEC (DMR 1720256) and Center for Scientific Computing (CNS 1725797, DMR 1720256). E. E. Foley and V. C. Wu were supported by the NSF Graduate Research Fellowship Program under Grant No. DGE 1650114. This work is supported by an NSF CAREER award under Grant No. DMR 2141754. Euchner, O. Clemens, and M.A. Reddy, Npt Comput. Mater. 5 31 (2019).Park, Y. Lee, M.-K. Cho, J. Kang, W. Ko, Y.H. Jung, T.-Y. Jeon, J. Hong, H. Kim, S.-T. Myung, and J. Kim, Energy Environ. Sci. 14 1469-1479 (2021).K. Dey, N. Barman, S. Ghosh, S. Sarkar, S.C. Peter, P. Senguttuvan, Chem. Mater. 31 295-299 (2019).Kang, J. Ahn, H. Park, W. Ko, Y. Lee, S. Lee, S. Lee, S.-K. Jung, J. Kim, J. Kang, J. Ahn, H. Park, W. Ko, Y. Lee, S. Lee, J. Kim and S.-K. Jung, Adv. Funct. Mater. 32 2201816 (2022). Fig. 1 , Charge- discharge curve for Na2Fe2F7 and the weberite structure. Figure 1

Tailored Chemical Reactivity Probes for Systemic Imaging of Aldehydes in Fibroproliferative Diseases.

During fibroproliferation, protein-associated extracellular aldehydes are formed by the oxidation of lysine residues on extracellular matrix proteins to form the aldehyde allysine. Here we report three Mn(II)-based, small-molecule magnetic resonance probes that contain α-effect nucleophiles to target allysine in vivo and report on tissue fibrogenesis. We used a rational design approach to develop turn-on probes with a 4-fold increase in relaxivity upon targeting. The effects of aldehyde condensation rate and hydrolysis kinetics on the performance of the probes to detect tissue fibrogenesis non-invasively in mouse models were evaluated by a systemic aldehyde tracking approach. We showed that, for highly reversible ligations, off-rate was a stronger predictor of in vivo efficiency, enabling histologically validated, three-dimensional characterization of pulmonary fibrogenesis throughout the entire lung. The exclusive renal elimination of these probes allowed for rapid imaging of liver fibrosis. Reducing the hydrolysis rate by forming an oxime bond with allysine enabled delayed phase imaging of kidney fibrogenesis. The imaging efficacy of these probes, coupled with their rapid and complete elimination from the body, makes them strong candidates for clinical translation.

Site-Specific Introduction of Alanines for the Nuclear Magnetic Resonance Investigation of Low-Complexity Regions and Large Biomolecular Assemblies.

Nuclear magnetic resonance (NMR) studies of large biomolecular machines and highly repetitive proteins remain challenging due to the difficulty of assigning frequencies to individual nuclei. Here, we present an efficient strategy to address this challenge by engineering a Pyrococcus horikoshii tRNA/alanyl-tRNA synthetase pair that enables the incorporation of up to three isotopically labeled alanine residues in a site-specific manner using in vitro protein expression. The general applicability of this approach for NMR assignment has been demonstrated by introducing isotopically labeled alanines into four distinct proteins: huntingtin exon-1, HMA8 ATPase, the 300 kDa molecular chaperone ClpP, and the alanine-rich Phox2B transcription factor. For large protein assemblies, our labeling approach enabled unambiguous assignments while avoiding potential artifacts induced by site-specific mutations. When applied to Phox2B, which contains two poly-alanine tracts of nine and twenty alanines, we observed that the helical stability is strongly dependent on the homorepeat length. The capacity to selectively introduce alanines with distinct labeling patterns is a powerful tool to probe structure and dynamics of challenging biomolecular systems.

A gerincvelő primer intramedulláris melanomája. Esetismertetés

Authors report the case of a79 year old man. After weakness, paraesthesia and walking disturbances developing within weeks he was admitted to the Neurology Department of our institution. Upon negativity of Computed Tomography the Magnetic Resonance Investigation of the spinal cord revealed space constrictor process corresponding to thoracic vertebrae X- XI. This mass wasremoved surgically. Histology supplemented by immuno-histochemistry had proved malignant melanoma. Genetic test out of the removed neoplastic tissue was negative to BRAF-V600 E. The repeated thoroughly performed checks on the entire integument as well as negativity of the ophthalmic status has raised the possibility of primary melanoma originated from the spinal cord. No lymph node metastasiswas detected.Aftersurgery targeted X-ray irradiation was performed, followed by Pembrolizumab administration in monotherapy. This treatment was, however suspended due to rapidly developing side effects. As next Carboplatin therapy was started which was stopped after the 5th cycle due to side effects. The temporary remission has lasted for 7 months but the initial symptoms had returned with increasing pain. From this time urinary infection and disturbance of intestinal passage have dominated the clinical picture. Decubital ulceration and sepsis developed and the patient died 21 months after first appearance of clinical symptoms. Extreme rarity and poor survival not exceeding 5 years are characteristics of the of reported cases