Systematic identification of gene combinations to target in innate immune cells to enhance T cell activation.

Genetic engineering of immune cells has opened new avenues for improving their functionality but it remains a challenge to pinpoint which genes or combination of genes are the most beneficial to target. Here, we conduct High Multiplicity of Perturbations and Cellular Indexing of Transcriptomes and Epitopes (HMPCITE-seq) to find combinations of genes whose joint targeting improves antigen-presenting cell activity and enhances their ability to activate T cells. Specifically, we perform two genome-wide CRISPR screens in bone marrow dendritic cells and identify negative regulators of CD86, that participate in the co-stimulation programs, including Chd4, Stat5b, Egr2, Med12, and positive regulators of PD-L1, that participate in the co-inhibitory programs, including Sptlc2, Nckap1l, and Pi4kb.

Long-range potentials and dipole moments of the CO electronic states converging to the ground dissociation limit.

The asymptotic, R → ∞, behavior of the potential-energy and dipole-moment functions (PEFs and DMFs) for all six (1,2)Σ+, (1,2)Π, Σ-, and Δ electronic states converging to the ground C(3P) + O(3P) dissociation limit of the CO molecule are studied in the framework of long-range (LR) perturbation theory. The analytical expressions for the leading coefficients of the LR expansion, C5/R5 for PEF and d4/R4 for DMF, in terms of the atomic quadrupole constants and static dipole polarizabilities are derived. The exact relationships between the LR coefficients for the states of different spatial symmetry are established as well.

Intensity anomalies in the rotational and ro-vibrational spectra of diatomic molecules.

We study the anomalies in the distributions of intensities of transitions in the purely rotational bands and the rotational branches of the vibrational bands within the unperturbed ground electronic states in spectra of diatomic molecules. While normally these distributions follow smooth patterns, sudden drops in intensity values are often observed. We analyze the origin of these anomalies in HF, DF, and CO and find that they are predominantly associated with specific forms of the dipole-moment functions (DMFs).

Peculiarities of high-overtone transition probabilities in carbon monoxide revealed by high-precision calculation.

In the recent work devoted to the calculation of the rovibrational line list of the CO molecule [G. Li et al., Astrophys.

Mechanisms of generation of local ΔpH in mitochondria and bacteria.

The concepts of global and local coupling between proton generators, the enzymes of the respiratory chain, and the consumer, the ATP synthase, coexist in the theory of oxidative phosphorylation. Global coupling is trivial proton transport via the aqueous medium, whereas local coupling implies that the protons pumped are consumed before they escape to the bulk phase. In this work, the conditions for the occurrence of local coupling are explored.

Mechanism of long-range proton translocation along biological membranes.

Recent experiments suggest that protons can travel along biological membranes up to tens of micrometers, but the mechanism of transport is unknown. To explain such a long-range proton translocation we describe a model that takes into account the coupled bulk diffusion that accompanies the migration of protons on the surface. We show that protons diffusing at or near the surface before equilibrating with the bulk desorb and re-adsorb at the surface thousands of times, giving rise to a power-law desorption kinetics.

Towards understanding the nature of the intensities of overtone vibrational transitions.

The overtone vibrational transitions, i.e., transitions between states separated by more than one vibrational quantum play important role in many fields of physics and chemistry.

Proton diffusion along biological membranes.

Biological surfaces are known to be capable of retaining protons and facilitating their lateral diffusion. Since the surface dynamically exchanges protons with the bulk, the proton movement from a source to a target at the surface acquires a complicated pattern of coupled surface and bulk (2D + 3D) diffusion of which the main feature is that the surface acts as a proton-collecting antenna enhancing the proton flux from the bulk. A phenomenological model of this process is reviewed and its applications to recent experiments on lipid bilayers and small unilaminar vesicles are discussed.

Determination of the intrinsic redox potentials of FeS centers of respiratory complex I from experimental titration curves.

Recently, Euro et al. [Biochem. 47, 3185 (2008) ] have reported titration data for seven of nine FeS redox centers of complex I from Escherichiacoli.

Electrostatics of the FeS clusters in respiratory complex I.

Respiratory complex I couples the transfer of electrons from NADH to ubiquinone and the translocation of protons across the mitochondrial membrane. A detailed understanding of the midpoint reduction potentials (E(m)) of each redox center and the factors which influence those potentials are critical in the elucidation of the mechanism of electron transfer in this enzyme. We present accurate electrostatic interaction energies for the iron-sulfur (FeS) clusters of complex I to facilitate the development of models and the interpretation of experiments in connection to electron transfer (ET) in this enzyme.

Theoretical and computational analysis of the membrane potential generated by cytochrome c oxidase upon single electron injection into the enzyme.

We have developed theory and the computational scheme for the analysis of the kinetics of the membrane potential generated by cytochrome c oxidase upon single electron injection into the enzyme. The theory allows one to connect the charge motions inside the enzyme to the membrane potential observed in the experiments by using data from the "dielectric topography" map of the enzyme that we have created. The developed theory is applied for the analysis of the potentiometric data recently reported by the Wikström group [I.

Protein dynamics control of electron transfer in photosynthetic reaction centers from Rps. sulfoviridis.

In the cycle of photosynthetic reaction centers, the initially oxidized special pair of bacteriochlorophyll molecules is subsequently reduced by an electron transferred over a chain of four hemes of the complex. Here, we examine the kinetics of electron transfer between the proximal heme c-559 of the chain and the oxidized special pair in the reaction center from Rps. sulfoviridis in the range of temperatures from 294 to 40 K.

[Relationship between microelements content of drinkable water and nephrolithiasis formation in Moscow region residents].

The article covers theoretical and practical matters on prevalence, incidence of nephrolithiasis in Moscow region and influencing ecological hazards. Predictive role of those matters is evaluated. The author presented features of drinkable water in Moscow region and revealed changes in nephrolithiasis prevalence in accordance with antropogenous load.

Role of viscosity and permeability of the erythrocyte plasma membrane in changes in oxygen-binding properties of hemoglobin during diabetes mellitus.

Changes in viscosity and permeability of the plasma membrane and conformation of erythrocyte hemoglobin hematoporphyrin were found in patients with diabetes mellitus. The decrease in oxygen binding and increase in deoxyhemoglobin concentration during diabetes mellitus were accompanied by changes in viscosity and permeability of the membrane for Na+, H+, Ca2+, and K+. Our results suggest that oxygen-binding properties of hemoglobin depend on viscosity and permeability of the erythrocyte plasma membrane.

The magnetic field effect in the presence of the electric field on fluorescence of a methylene-linked compound of pyrene and n,n-dimethylaniline doped in a polymer film.

Recent experimental data by Mizoguchi and Ohta are analyzed under the assumption of fast equilibrium between the locally excited (LE), radical-ion-pair (RIP), and exciplex states. In the absence of the equilibrium, no magnetic field effect on the LE fluorescence would be observed. Owing to the equilibrium, the relative electric-field-induced changes of the quantum yields of the LE and exciplex emissions as functions of the magnetic field are linearly connected to each other.

Analysis of the kinetics of the membrane potential generated by cytochrome c oxidase upon single electron injection.

In a recent work from this group (Popovic, D. M.; Stuchebrukhov A.

Kinetics of proton diffusion in the regimes of fast and slow exchange between the membrane surface and the bulk solution.

The phenomenological model developed in our recent publications [9,10] is used to investigate the kinetics of proton diffusion from a source to a detector on the membrane surface. In most cases the observed kinetics shows a single diffusional maximum with the exponential ascending front and the power-law descending tail. The kinetics depends on the distance between the source and the detector.

[Theoretical analysis of redox-dependent protonation of hema a and Cu(A) in cytochrome c oxidase and CO-inhibited binuclear center].

One of the proposed mechanisms of functioning of cytochrome c oxidase (COX) postulates that heme a is the element pumping protons across the membrane. It is generally believed that, to support this mechanism, a substantial proton uptake/release should exist upon heme a reduction/oxidation. Two direct measurements of proton uptake/release in oxidation/reduction of heme a in CO-bound mixed-valence COX were recently reported.

Proton transport via the membrane surface.

Some proton pumps, such as cytochrome c oxidase (C(c)O), translocate protons across biological membranes at a rate that considerably exceeds the rate of proton transport to the entrance of the proton-conducting channel via bulk diffusion. This effect is usually ascribed to a proton-collecting antenna surrounding the channel entrance. In this paper, we consider a realistic phenomenological model of such an antenna.

[A comparative study of conservative treatment schemes in chronic tonsillitis in children].

Three schemes of conservative treatment of chronic tonsillitis in children are compared. Chelidonium majus L. tincture improved tonsillar function, cellular and humoral immunity, nonspecific resistance, promoted a reduction in the number of recurrences.

Effect of protein dynamics on biological electron transfer.

Computer simulations of the effect of protein dynamics on the long distance tunneling mediated by the protein matrix have been carried out for a Ru-modified (His 126) azurin molecule. We find that the tunneling matrix element is a sensitive function of the atomic configuration of the part of the protein matrix in which tunneling currents (pathways) are localized. Molecular dynamics simulations show that fluctuations of the matrix element can occur on a time scale as short as 10 fs.

[The indices of central and peripheral hemodynamics and of autonomic nervous system function in subjects with arterial hypertension working under different manufacturing conditions].

As many as 318 persons with arterial hypertension working at an industrial enterprise, engaged in agricultural production, and in the sphere of mental work, were examined. The control group consisted of 40 essentially healthy subjects from the above cohorts. The following subgroups were identified in the groups observed: borderline arterial hypertension, I and II stage hypertensive disease.

[Prevention and treatment of early complications of surgical treatment of peptic ulcer].

An experience with the operative treatment of 1620 patients has shown that incidence of postoperative complications can be reduced by using active aspiration of the gastric stump content, early intestinal feeding, autohemotransfusions for the substitution of the intraoperative blood loss.