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1.
Front Vet Sci ; 10: 1166032, 2023.
Article in English | MEDLINE | ID: mdl-37649563

ABSTRACT

Introduction: Cranial and upper-airway anatomy of short-nosed, flat-faced brachycephalic dogs predisposes them to brachycephalic obstructive airway syndrome (BOAS). Periodic apnoea increased inspiratory resistance, and an inability to thermoregulate effectively are characteristic of BOAS, but internationally accepted objective markers of BOAS severity are missing. The objective of this study was to compare the selected blood parameters between non-brachycephalic (NC) and brachycephalic (BC) dogs, exploring the possibility of developing a blood test for BOAS severity grading in the future. Methods: We evaluated blood biochemistry, complete blood cell counts, red blood cell (RBC) indices, reticulocyte counts, a blood-born marker of intermittent hypoxia (glutathione, NO production), RBC hydration, deformability, and blood markers of metabolic changes and stress between BC (n = 18) and NC (meso- and dolichocephalic, n = 22) dogs. Results: Reticulocyte counts and the abundance of middle-fluorescence immature reticulocytes were significantly (p < 0.05) higher in BC dogs compared to NC dogs. BC dogs had significantly more NO-derived NO2-/NO3- in plasma than NC dogs. RBCs of BC dogs were shedding significantly more membrane, as follows from the intensity of eosin maleimide staining, and had a significantly higher mean corpuscular hemoglobin concentration than NC dogs. Intracellular reduced glutathione content in RBCs of BC dogs was significantly lower, while plasma lactate was significantly higher in BC dogs compared to NC dogs. Plasma cholesterol and triglycerides were significantly lower, and cortisol was significantly higher in BC dogs compared to NC dogs. Eosinophil counts were significantly lower and the neutrophil-to-lymphocyte ratio was higher in BC dogs compared to NC dogs. Discussion: Taken together, our findings suggest that the brachycephalic phenotype in dogs is associated with alterations at the level of blood cells and, systemically, with oxidation and metabolic changes. The parameters identified within this study should be further investigated for their potential as objective indicators for BOAS.

2.
Cells ; 12(7)2023 03 24.
Article in English | MEDLINE | ID: mdl-37048064

ABSTRACT

Methemoglobinemia is an acquired or inherited condition resulting from oxidative stress or dysfunction of the NADH-cytochrome b5 reductase or associated pathways. This study describes the clinical, pathophysiological, and molecular genetic features of a cat with hereditary methemoglobinemia. Whole genome sequencing and mRNA transcript analyses were performed in affected and control cats. Co-oximetry, ektacytometry, Ellman's assay for reduced glutathione concentrations, and CYB5R activity were assessed. A young adult European domestic shorthair cat decompensated at induction of anesthesia and was found to have persistent methemoglobinemia of 39 ± 8% (reference range < 3%) of total hemoglobin which could be reversed upon intravenous methylene blue injection. The erythrocytic CYB5R activity was 20 ± 6% of normal. Genetic analyses revealed a single homozygous base exchange at the beginning of intron 3 of the CYB5R3 gene, c.226+5G>A. Subsequent mRNA studies confirmed a splice defect and demonstrated expression of two mutant CYB5R3 transcripts. Erythrocytic glutathione levels were twice that of controls. Mild microcytosis, echinocytes, and multiple Ca2+-filled vesicles were found in the affected cat. Erythrocytes were unstable at high osmolarities although highly deformable as follows from the changes in elongation index and maximal-tolerated osmolarity. Clinicopathological presentation of this cat was similar to other cats with CYB5R3 deficiency. We found that methemoglobinemia is associated with an increase in red blood cell fragility and deformability, glutathione overload, and morphological alterations typical for stress erythropoiesis.


Subject(s)
Methemoglobinemia , Cats , Animals , Methemoglobinemia/genetics , Methemoglobinemia/drug therapy , Methemoglobinemia/veterinary , Erythrocytes , Methylene Blue , RNA, Messenger/therapeutic use , Glutathione
3.
J Chem Theory Comput ; 17(9): 5684-5703, 2021 Sep 14.
Article in English | MEDLINE | ID: mdl-34469685

ABSTRACT

In this work, we demonstrate how to efficiently compute the one- and two-body reduced density matrices within the spin-adapted full configuration interaction quantum Monte Carlo (FCIQMC) method, which is based on the graphical unitary group approach (GUGA). This allows us to use GUGA-FCIQMC as a spin-pure configuration interaction (CI) eigensolver within the complete active space self-consistent field (CASSCF) procedure and hence to stochastically treat active spaces far larger than conventional CI solvers while variationally relaxing orbitals for specific spin-pure states. We apply the method to investigate the spin ladder in iron-sulfur dimer and tetramer model systems. We demonstrate the importance of the orbital relaxation by comparing the Heisenberg model magnetic coupling parameters from the CASSCF procedure to those from a CI-only (CASCI) procedure based on restricted open-shell Hartree-Fock orbitals. We show that the orbital relaxation differentially stabilizes the lower-spin states, thus enlarging the coupling parameters with respect to the values predicted by ignoring orbital relaxation effects. Moreover, we find that, while CASCI results are well fit by a simple bilinear Heisenberg Hamiltonian, the CASSCF eigenvalues exhibit deviations that necessitate the inclusion of biquadratic terms in the model Hamiltonian.

4.
J Phys Chem A ; 125(22): 4727-4740, 2021 Jun 10.
Article in English | MEDLINE | ID: mdl-34048648

ABSTRACT

Polynuclear transition-metal (PNTM) clusters owe their catalytic activity to numerous energetically low-lying spin states and stable oxidation states. The characterization of their electronic structure represents one of the greatest challenges of modern chemistry. We propose a theoretical framework that enables the resolution of targeted electronic states with ease and apply it to two [Fe(III)4S4] cubanes. Through direct access to their many-body wave functions, we identify important correlation mechanisms and their interplay with the geometrical distortions observed in these clusters, which are core properties in understanding their catalytic activity. The simulated magnetic coupling constants predicted by our strategy allow us to make qualitative connections between spin interactions and geometrical distortions, demonstrating its predictive power. Moreover, despite its simplicity, the strategy provides magnetic coupling constants in good agreement with the available experimental ones. The complexes are intrinsically frustrated anti-ferromagnets, and the obtained spin structures together with the geometrical distortions represent two possible ways to release spin frustration (spin-driven Jahn-Teller distortion). Our paradigm provides a simple, yet rigorous, route to uncover the electronic structure of PNTM clusters and may be applied to a wide variety of such clusters.

5.
J Chem Phys ; 154(16): 164302, 2021 Apr 28.
Article in English | MEDLINE | ID: mdl-33940817

ABSTRACT

Accurate ab initio calculations of 3d transition metal monoxide molecules have attracted extensive attention because of their relevance in physical and chemical science as well as theoretical challenges in treating strong electron correlation. Meanwhile, recent years have witnessed the rapid development of the full configuration interaction quantum Monte Carlo (FCIQMC) method to tackle electron correlation. In this study, we carry out FCIQMC simulations to ScO, TiO, and VO molecules and obtain accurate descriptions of 13 low-lying electronic states (ScO 2Σ+, 2Δ, 2Π; TiO 3Δ, 1Δ, 1Σ+, 3Π, 3Φ; VO 4Σ-, 4Φ, 4Π, 2Γ, 2Δ), including states that have significant multi-configurational character. The FCIQMC results are used to assess the performance of several other wave function theory and density functional theory methods. Our study highlights the challenging nature of the electronic structure of transition metal oxides and demonstrates FCIQMC as a promising technique going forward to treat more complex transition metal oxide molecules and materials.

6.
J Chem Phys ; 153(20): 204704, 2020 Nov 28.
Article in English | MEDLINE | ID: mdl-33261489

ABSTRACT

Oxygen vacancies are ubiquitous in TiO2 and play key roles in catalysis and magnetism applications. Despite being extensively investigated, the electronic structure of oxygen vacancies in TiO2 remains controversial both experimentally and theoretically. Here, we report a study of a neutral oxygen vacancy in TiO2 using state-of-the-art quantum chemical electronic structure methods. We find that the ground state is a color center singlet state in both the rutile and the anatase phases of TiO2. Specifically, embedded coupled cluster with singles, doubles, and perturbative triples calculations find, for an oxygen vacancy in rutile, that the lowest triplet state energy is 0.6 eV above the singlet state, and in anatase, the triplet state energy is higher by 1.4 eV. Our study provides fresh insights into the electronic structure of the oxygen vacancy in TiO2, clarifying earlier controversies and potentially inspiring future studies of defects with correlated wave function theories.

7.
J Chem Phys ; 153(3): 034107, 2020 Jul 21.
Article in English | MEDLINE | ID: mdl-32716189

ABSTRACT

We present NECI, a state-of-the-art implementation of the Full Configuration Interaction Quantum Monte Carlo (FCIQMC) algorithm, a method based on a stochastic application of the Hamiltonian matrix on a sparse sampling of the wave function. The program utilizes a very powerful parallelization and scales efficiently to more than 24 000 central processing unit cores. In this paper, we describe the core functionalities of NECI and its recent developments. This includes the capabilities to calculate ground and excited state energies, properties via the one- and two-body reduced density matrices, as well as spectral and Green's functions for ab initio and model systems. A number of enhancements of the bare FCIQMC algorithm are available within NECI, allowing us to use a partially deterministic formulation of the algorithm, working in a spin-adapted basis or supporting transcorrelated Hamiltonians. NECI supports the FCIDUMP file format for integrals, supplying a convenient interface to numerous quantum chemistry programs, and it is licensed under GPL-3.0.

8.
J Chem Phys ; 153(2): 024109, 2020 Jul 14.
Article in English | MEDLINE | ID: mdl-32668948

ABSTRACT

PySCF is a Python-based general-purpose electronic structure platform that supports first-principles simulations of molecules and solids as well as accelerates the development of new methodology and complex computational workflows. This paper explains the design and philosophy behind PySCF that enables it to meet these twin objectives. With several case studies, we show how users can easily implement their own methods using PySCF as a development environment. We then summarize the capabilities of PySCF for molecular and solid-state simulations. Finally, we describe the growing ecosystem of projects that use PySCF across the domains of quantum chemistry, materials science, machine learning, and quantum information science.

9.
EJHaem ; 1(1): 23-34, 2020 Jul.
Article in English | MEDLINE | ID: mdl-35847705

ABSTRACT

An increase in abundance and activity of N-methyl D-aspartate receptors (NMDAR) was previously reported for red blood cells (RBCs) of sickle cell disease (SCD) patients. Increased Ca2+ uptake through the receptor supported dehydration and RBC damage. In a pilot phase IIa-b clinical trial MemSID, memantine, a blocker of NMDAR, was used for treatment of four patients for 12 months. Two more patients that have enrolled into the study did not finish it. One of them had psychotic event following the involuntary overdose of the drug, whereas the other had vertigo and could not comply to the trial visits schedule. Acute and durable responses of RBCs of SCD patients to daily oral administration of memantine were monitored. Markers of RBC turnover, changes in cell density, and alterations in ion handling and RBC morphology were assessed. Acute transient shifts in intracellular Ca2+, volume and density, and reduction in plasma lactate dehydrogenate activity were observed already within the first month of treatment. Durable effects of memantine included (a) decrease in reticulocyte counts, (b) reduction in reticulocyte hemoglobinization, (c) advanced membrane maturation and its stabilization as follows from reduction in the number of NMDAR per cell and reduction in hemolysis, and (iv) rehydration and decrease in K+ leakage from patients' RBC. Memantine therapy resulted in reduction in number of cells with sickle morphology that was sustained at least over 2 months after therapy was stopped indicating an improvement in RBC longevity.

10.
J Chem Theory Comput ; 15(11): 5925-5964, 2019 Nov 12.
Article in English | MEDLINE | ID: mdl-31509407

ABSTRACT

In this Article we describe the OpenMolcas environment and invite the computational chemistry community to collaborate. The open-source project already includes a large number of new developments realized during the transition from the commercial MOLCAS product to the open-source platform. The paper initially describes the technical details of the new software development platform. This is followed by brief presentations of many new methods, implementations, and features of the OpenMolcas program suite. These developments include novel wave function methods such as stochastic complete active space self-consistent field, density matrix renormalization group (DMRG) methods, and hybrid multiconfigurational wave function and density functional theory models. Some of these implementations include an array of additional options and functionalities. The paper proceeds and describes developments related to explorations of potential energy surfaces. Here we present methods for the optimization of conical intersections, the simulation of adiabatic and nonadiabatic molecular dynamics, and interfaces to tools for semiclassical and quantum mechanical nuclear dynamics. Furthermore, the Article describes features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism, and properties. Finally, the paper describes a number of built-in and add-on features to support the OpenMolcas platform with postcalculation analysis and visualization, a multiscale simulation option using frozen-density embedding theory, and new electronic and muonic basis sets.

11.
Nutrients ; 11(7)2019 Jul 18.
Article in English | MEDLINE | ID: mdl-31323779

ABSTRACT

This study aimed to investigate the influence of a single dose of either beetroot juice (BR) or sodium nitrate (NIT) on performance in a 10 km handcycling time trial (TT) in able-bodied individuals and paracyclists. In total, 14 able-bodied individuals [mean ± SD; age: 28 ± 7 years, height: 183 ± 5 cm, body mass (BM): 82 ± 9 kg, peak oxygen consumption (VO2peak): 33.9 ± 4.2 mL/min/kg] and eight paracyclists (age: 40 ± 11 years, height: 176 ± 9cm, BM: 65 ± 9 kg, VO2peak: 38.6 ± 10.5 mL/min/kg) participated in the study. All participants had to perform three TT on different days, receiving either 6 mmol nitrate as BR or NIT or water as a placebo. Time-to-complete the TT, power output (PO), as well as oxygen uptake (VO2) were measured. No significant differences in time-to-complete the TT were found between the three interventions in able-bodied individuals (p = 0.80) or in paracyclists (p = 0.61). Furthermore, VO2 was not significantly changed after the ingestion of BR or NIT in either group (p < 0.05). The PO to VO2 ratio was significantly higher in some kilometers of the TT in able-bodied individuals (p < 0.05). The ingestion of BR or NIT did not increase handcycling performance in able-bodied individuals or in paracyclists.


Subject(s)
Beta vulgaris/chemistry , Fruit and Vegetable Juices , Nitrates/administration & dosage , Adult , Blood Pressure , Dietary Supplements , Heart Rate , Humans , Male , Middle Aged , Oxygen/metabolism , Plant Roots/chemistry , Spinal Cord Injuries
12.
J Med Virol ; 90(1): 41-49, 2018 01.
Article in English | MEDLINE | ID: mdl-28842994

ABSTRACT

The producers of influenza vaccines are not capable today to meet the global demand for an influenza vaccine in case of pandemic, so the World Health Organization recommends to develop the own influenza vaccine production in each country. A domestic preservative- and adjuvant-free trivalent split vaccine against seasonal influenza was developed at the Research Institute for Biological Safety Problems. The paper presents the results of assessing safety and immunogenicity of the influenza split vaccine after single immunization of healthy volunteers aged 18-50 years in the course of Phase I Clinical Trials. This study was randomized, blind, and placebo-controlled. The volunteers were intramuscularly vaccinated with a dose of split vaccine or placebo. The study has shown that all local and systemic reactions had low degree of manifestation and short-term character, so there was no need in medication. Serious side effects were not observed. On day 21 post vaccination the portion of vaccinated persons with fourfold seroconversions to influenza А/H1N1pdm09 virus was 100.0%, to influenza А/H3N2 virus-95.5%, to influenza B virus-81.8%, and in placebo group this index was 0%. Seroprotection rates against influenza А/H1N1pdm09, А/H3N2 and B viruses were 95.5, 86.3, and 72.7%, respectively. Geometric mean titers (GMT) of antibodies by day 21 post vaccination reached 175.7 for influenza А/H1N1pdm09 virus, 64.2 for influenza А/H3N2 virus, and 37.6 for influenza B virus; in placebo group GMT growth was not observed. So, the seasonal influenza split vaccine is well tolerated and fits all immunogenicity criteria for human influenza vaccines.


Subject(s)
Immunogenicity, Vaccine , Influenza Vaccines/adverse effects , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Adjuvants, Immunologic , Adolescent , Adult , Antibodies, Viral/blood , Female , Humans , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/immunology , Influenza B virus/immunology , Influenza Vaccines/administration & dosage , Influenza, Human/immunology , Influenza, Human/virology , Male , Middle Aged , Pandemics/prevention & control , Preservatives, Pharmaceutical , Seasons , Vaccination , Vaccines, Inactivated/administration & dosage , Young Adult
13.
Hum Vaccin Immunother ; 14(3): 609-614, 2018 03 04.
Article in English | MEDLINE | ID: mdl-29112488

ABSTRACT

BACKGROUND: The study was aimed at comparative evaluation of seasonal influenza vaccine RIBSP versus commercial vaccine VAXIGRIP® for immunogenicity and safety in the course of clinical trial phase II on healthy volunteers aged 18-60 years. METHODS: The trial involved 150 subjects in randomized 2:1 groups that received either RIBSP vaccine or comparator vaccine VAXIGRIP®. One dose (0.5 ml) of either vaccine contained 15 µg of hemagglutinin of each influenza virus strain recommended by WHO for the Northern hemisphere in 2016-2017 flu season. The observation period lasted 21 day. The trial was registered at ClinicalTrials.gov identifier NCT 03016143. RESULTS: Assessment of immunogenic activity of the vaccine under study showed that in 21 day the portion of participants with 4-fold seroconversions was 87.0% to A/H1N1; 63.0% to A/H3N2 and 59.0% to B virus. Antibody titer increase factor in the group of subjects that received RIBSP vaccine was 23.3 for A/H1N1; 4.4 for A/H3N2 and 4.5 for B virus. The volunteers that received RIBSP vaccine demonstrated 95% seroprotection level against A/H1N1; 84% against A/H3N2 and 80% against B virus. RIBSP vaccine met the CHMP criteria of the Committee for Medicinal Products for Human Use (CPMP/BWP/214/96). In the course of evaluating the vaccine safety no serious undesirable effects were recorded. All changes of laboratory data were slight and single in most cases. All recorded local reactions have been light in character and these have been predicted reactions observed at vaccination against influenza. CONCLUSION: Comparison of the allantoic inactivated split vaccine obtained in vaccines RIBSP and VAXIGRIP®, showed similar immunogenic activity. Both vaccines were safe for the study participants.


Subject(s)
Antibody Formation/immunology , Influenza Vaccines/adverse effects , Influenza Vaccines/immunology , Influenza, Human/immunology , Influenza, Human/prevention & control , Preservatives, Pharmaceutical/adverse effects , Antibodies, Viral/immunology , Female , Hemagglutination Inhibition Tests/methods , Humans , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/immunology , Influenza B virus/immunology , Kazakhstan , Male , Seasons , Vaccination/methods , Vaccines, Inactivated/immunology
14.
Redox Biol ; 13: 310-319, 2017 10.
Article in English | MEDLINE | ID: mdl-28601781

ABSTRACT

Our previous findings suggested that reversible thiol modifications of cysteine residues within the actuator (AD) and nucleotide binding domain (NBD) of the Na,K-ATPase may represent a powerful regulatory mechanism conveying redox- and oxygen-sensitivity of this multifunctional enzyme. S-glutathionylation of Cys244 in the AD and Cys 454-458-459 in the NBD inhibited the enzyme and protected cysteines' thiol groups from irreversible oxidation under hypoxic conditions. In this study mutagenesis approach was used to assess the role these cysteines play in regulation of the Na,K-ATPase hydrolytic and signaling functions. Several constructs of mouse α1 subunit of the Na,K-ATPase were produced in which Cys244, Cys 454-458-459 or Cys 244-454-458-459 were replaced by alanine. These constructs were expressed in human HEK293 cells. Non-transfected cells and those expressing murine α1 subunit were exposed to hypoxia or treated with oxidized glutathione (GSSG). Both conditions induced inhibition of the wild type Na,K-ATPase. Enzymes containing mutated mouse α1 lacking Cys244 or all four cysteines (Cys 244-454-458-459) were insensitive to hypoxia. Inhibitory effect of GSSG was observed for wild type murine Na,K-ATPase, but was less pronounced in Cys454-458-459Ala mutant and completely absent in the Cys244Ala and Cys 244-454-458-459Ala mutants. In cells, expressing wild type enzyme, ouabain induced activation of Src and Erk kinases under normoxic conditions, whereas under hypoxic conditions this effect was inversed. Cys454-458-459Ala substitution abolished Src kinase activation in response to ouabain treatment, uncoupled Src from Erk signaling, and interfered with O2-sensitivity of Na,K-ATPase signaling function. Moreover, modeling predicted that S-glutathionylation of Cys 458 and 459 should prevent inhibitory binding of Src to NBD. Our data indicate for the first time that cysteine residues within the AD and NBD influence hydrolytic as well as receptor function of the Na,K-ATPase and alter responses of the enzyme to hypoxia or upon treatment with cardiotonic steroids.


Subject(s)
Catalytic Domain , Sodium-Potassium-Exchanging ATPase/chemistry , Amino Acid Substitution , Cell Hypoxia , HEK293 Cells , Humans , Hydrolysis , MAP Kinase Signaling System , Oxygen/metabolism , Sodium-Potassium-Exchanging ATPase/genetics , Sodium-Potassium-Exchanging ATPase/metabolism
15.
J Med Virol ; 89(7): 1168-1173, 2017 07.
Article in English | MEDLINE | ID: mdl-28160490

ABSTRACT

The paper describes the results of preclinical testing of the preparation "Vaccine allantoic split-virus inactivated against seasonal influenza." Acute toxicity and local irritating effect, anaphylactic reactions to different antigens (vaccine and ovalbumin), delayed-type hypersensitivity to ram erythrocytes, humoral immune response in hemaggtination reaction, immunogenic activity was studied in laboratory animals of various species (mice, rats, guinea pigs). Comparative analysis of the results from testing immunogenic activity of the preparation under study and the commercial influenza vaccines was performed. The preclinical testing has demonstrated safety and immune response of the seasonal split influenza vaccine, so it may be recommended for clinical study on limited contingent of volunteers.


Subject(s)
Drug Evaluation, Preclinical , Influenza Vaccines/adverse effects , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Animals , Antibodies, Viral/blood , Erythrocytes , Guinea Pigs , Humans , Hypersensitivity, Delayed/prevention & control , Immunogenicity, Vaccine , Influenza A Virus, H1N1 Subtype/immunology , Influenza Vaccines/administration & dosage , Influenza Vaccines/chemistry , Influenza, Human/immunology , Mice , Orthomyxoviridae Infections/prevention & control , Preservatives, Pharmaceutical , Rats , Seasons , Sheep , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunology
16.
J Phys Condens Matter ; 29(3): 035502, 2017 Jan 25.
Article in English | MEDLINE | ID: mdl-27869641

ABSTRACT

In existing theoretical approaches to core-level excitations of transition-metal ions in solids relaxation and polarization effects due to the inner core hole are often ignored or described phenomenologically. Here we set up an ab initio computational scheme that explicitly accounts for such physics in the calculation of x-ray absorption and resonant inelastic x-ray scattering spectra. Good agreement is found with experimental transition-metal L-edge data for the strongly correlated d 9 cuprate Li2CuO2, for which we determine the absolute scattering intensities. The newly developed methodology opens the way for the investigation of even more complex d n electronic structures of group VI B to VIII B correlated oxide compounds.

17.
Sci Rep ; 6: 37925, 2016 11 30.
Article in English | MEDLINE | ID: mdl-27901091

ABSTRACT

Large anisotropic exchange in 5d and 4d oxides and halides open the door to new types of magnetic ground states and excitations, inconceivable a decade ago. A prominent case is the Kitaev spin liquid, host of remarkable properties such as protection of quantum information and the emergence of Majorana fermions. Here we discuss the promise for spin-liquid behavior in the 4d5 honeycomb halide α-RuCl3. From advanced electronic-structure calculations, we find that the Kitaev interaction is ferromagnetic, as in 5d5 iridium honeycomb oxides, and indeed defines the largest superexchange energy scale. A ferromagnetic Kitaev coupling is also supported by a detailed analysis of the field-dependent magnetization. Using exact diagonalization and density-matrix renormalization group techniques for extended Kitaev-Heisenberg spin Hamiltonians, we find indications for a transition from zigzag order to a gapped spin liquid when applying magnetic field. Our results offer a unified picture on recent magnetic and spectroscopic measurements on this material and open new perspectives on the prospect of realizing quantum spin liquids in d5 halides and oxides in general.

18.
Cell Calcium ; 60(4): 235-44, 2016 10.
Article in English | MEDLINE | ID: mdl-27292137

ABSTRACT

The N-methyl d-aspartate receptors (NMDARs) mediating Ca(2+) uptake upon stimulation with glutamate and glycine were recently discovered in red blood cells (RBC) of healthy humans. Activation of these receptors with agonists triggered transient Ca(2+)-dependent decrease in hemoglobin oxygen affinity in RBC suspension. The aim of this study was to assess the potential physiological relevance of this phenomenon. Two groups formed by either healthy untrained volunteers or endurance athletes were subjected to a stepwise incremental cycling test to exhaustion. Plasma glutamate levels, activity of the NMDARs, and hemoglobin O2 affinity were measured in blood samples obtained before and after the exercise in both groups. Increase in plasma glutamate levels following exercise was observed in both groups. Transient Ca(2+) accumulation in response to the NMDAR stimulation with NMDA and glycine was followed by facilitated Ca(2+) extrusion from the RBC and compensatory decrease in cytosolic Ca(2+) levels. Short-term activation of the receptors triggered a transient decrease in O2 affinity of hemoglobin in both groups. These exercise-induced responses were more pronounced in athletes compared to the untrained subjects. Athletes were initially presented with lower basal intracellular Ca(2+) levels and hemoglobin oxygen affinity compared to non-trained controls. High basal plasma glutamate levels were associated with induction of hemolysis and formation of echinocytes upon stimulation with the receptor agonists. These findings suggest that glutamate release occurring during exhaustive exercise bouts may acutely facilitate O2 liberation from hemoglobin and improve oxygen delivery to the exercising muscle.


Subject(s)
Amino Acids/blood , Athletes , Calcium/metabolism , Erythrocyte Membrane/metabolism , Erythrocytes/metabolism , Exercise , Adult , Female , Humans , Male , Young Adult
19.
Nat Commun ; 6: 7306, 2015 Jun 24.
Article in English | MEDLINE | ID: mdl-26105992

ABSTRACT

A promising route to tailoring the electronic properties of quantum materials and devices rests on the idea of orbital engineering in multilayered oxide heterostructures. Here we show that the interplay of interlayer charge imbalance and ligand distortions provides a knob for tuning the sequence of electronic levels even in intrinsically stacked oxides. We resolve in this regard the d-level structure of layered Sr2IrO4 by electron spin resonance. While canonical ligand-field theory predicts g||-factors less than 2 for positive tetragonal distortions as present in Sr2IrO4, the experiment indicates g|| is greater than 2. This implies that the iridium d levels are inverted with respect to their normal ordering. State-of-the-art electronic-structure calculations confirm the level switching in Sr2IrO4, whereas we find them in Ba2IrO4 to be instead normally ordered. Given the nonpolar character of the metal-oxygen layers, our findings highlight the tetravalent transition-metal 214 oxides as ideal platforms to explore d-orbital reconstruction in the context of oxide electronics.

20.
Transfusion ; 55(8): 1872-81, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25752902

ABSTRACT

BACKGROUND: Prolonged storage of red blood cells (RBCs) leads to storage lesions, which may impair clinical outcomes after transfusion. A hallmark of storage lesions is progressive echinocytic shape transformation, which can be partially reversed by washing in albumin solutions. Here we have investigated the impact of this shape recovery on biorheologic variables. STUDY DESIGN AND METHODS: RBCs stored hypothermically for 6 to 7 weeks were washed in a 1% human serum albumin (HSA) solution. RBC deformability was measured with osmotic gradient ektacytometry. The viscosity of RBC suspensions was measured with a Couette-type viscometer. The flow behavior of RBCs suspended at 40% hematocrit was tested with an artificial microvascular network (AMVN). RESULTS: Washing in 1% albumin reduced higher degrees of echinocytes and increased the frequency of discocytes, thereby shifting the morphologic index toward discocytosis. Washing also reduced RBC swelling. This shape recovery was not seen after washing in saline, buffer, or plasma. RBC shape normalization did not improve cell deformability measured by ektacytometry, but it tended to decrease suspension viscosities at low shear rates and improved the perfusion of an AMVN. CONCLUSIONS: Washing of stored RBCs in a 1% HSA solution specifically reduces echinocytosis, and this shape recovery has a beneficial effect on microvascular perfusion in vitro. Washing in 1% albumin may represent a new approach to improving the quality of stored RBCs and thus potentially reducing the likelihood of adverse clinical outcomes associated with transfusion of blood stored for longer periods of time.


Subject(s)
Blood Preservation/methods , Erythrocyte Transfusion , Erythrocytes/drug effects , Serum Albumin/pharmacology , Adenine/pharmacology , Adenosine Triphosphate/blood , Buffers , Cell Shape , Erythrocyte Indices , Erythrocytes/cytology , Erythrocytes, Abnormal/ultrastructure , Glucose/pharmacology , Glutathione/blood , Guanosine/pharmacology , Hemorheology , Humans , In Vitro Techniques , Mannitol/pharmacology , Models, Anatomic , Oxidation-Reduction , Perfusion , Plasma , Refrigeration , Sodium Chloride/pharmacology , Solutions
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