NMR studies of membrane structure and dynamics

Over the past decade, there has been considerable interest in the motional state of the phospholipid bilayer membrane. The motivation underlying these efforts has been the contention that the phospholipid bilayer is the basic matrix in which membrane proteins are embedded to form the biological membrane, and that the permeability and mechanical properties of the membrane, as well as the enzymatic activity of membrane proteins, are dependent upon the fluidity of the bilayer, especially the motional state of the hydrocarbon chains

Structure of cytochrome a3-Cua3 couple in cytochrome c oxidase as revealed by nitric oxide binding studies

The addition of NO to oxidized cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) causes the appearance of a high-spin heme electron paramagnetic resonance (EPR) signal due to cytochrome a3. This suggests that NO coordinates to Cu{a3}+2 and breaks the antiferromagnetic couple by forming a cytochrome a3+3-Cu{a3}+2-NO complex. The intensity of the high-spin cytochrome a3 signal depends on the method of preparation of the enzyme and maximally accounts for 58% of one heme. The effect of N3- on the cytochrome a3+3-Cu{a3}+2-NO complex is to reduce cytochrome a3 to the ferrous state, and this is followed by formation of a new complex that exhibits EPR signals characteristic of a triplet species. On the basis of optical and EPR results, a NO bridge between cytochrome a3+2 and Cu{a3}+2 is proposed-i.e., cytochrome a3+2-NO-Cu{a3}+2. The half-field transition observed at g = 4.34 in the EPR spectrum of this triplet species exhibits resolved copper hyperfine splittings with |A{}| = 0.020 cm-1, indicating that the Cu{a3}+2 in the cytochrome a3+2-NO-Cu{a3}+2 complex is similar to a type 2 copper site

Supervised machine learning based multi-task artificial intelligence classification of retinopathies

Artificial intelligence (AI) classification holds promise as a novel and affordable screening tool for clinical management of ocular diseases. Rural and underserved areas, which suffer from lack of access to experienced ophthalmologists may particularly benefit from this technology. Quantitative optical coherence tomography angiography (OCTA) imaging provides excellent capability to identify subtle vascular distortions, which are useful for classifying retinovascular diseases. However, application of AI for differentiation and classification of multiple eye diseases is not yet established. In this study, we demonstrate supervised machine learning based multi-task OCTA classification. We sought 1) to differentiate normal from diseased ocular conditions, 2) to differentiate different ocular disease conditions from each other, and 3) to stage the severity of each ocular condition. Quantitative OCTA features, including blood vessel tortuosity (BVT), blood vascular caliber (BVC), vessel perimeter index (VPI), blood vessel density (BVD), foveal avascular zone (FAZ) area (FAZ-A), and FAZ contour irregularity (FAZ-CI) were fully automatically extracted from the OCTA images. A stepwise backward elimination approach was employed to identify sensitive OCTA features and optimal-feature-combinations for the multi-task classification. For proof-of-concept demonstration, diabetic retinopathy (DR) and sickle cell retinopathy (SCR) were used to validate the supervised machine leaning classifier. The presented AI classification methodology is applicable and can be readily extended to other ocular diseases, holding promise to enable a mass-screening platform for clinical deployment and telemedicine.Comment: Supplemental material attached at the en

Doppler-free approach to optical pumping dynamics in the 6S1/2−5D5/26S_{1/2}- 5D_{5/2} electric quadrupole transition of Cesium vapor

The $6S_{1/2}-5D_{5/2}$ electric quadrupole transition is investigated in Cesium vapor at room temperature via nonlinear Doppler-free 6P-6S-5D three-level spectroscopy. Frequency-resolved studies of individual E2 hyperfine lines allow one to analyze optical pumping dynamics, polarization selection rules and line intensities. It opens the way to studies of transfer of light orbital angular momentum to atoms, and the influence of metamaterials on E2 line spectra.Comment: 4 pages, 5 figures, minor updates from previous versio

Coupling of atomic quadrupole transitions with resonant surface plasmons

We report on the coupling of an electric quadrupole transition in atom with plasmonic excitation in a nanostructured metallic metamaterial. The quadrupole transition at 685 nm in the gas of Cesium atoms is optically pumped, while the induced ground state population depletion is probed with light tuned on the strong electric dipole transition at 852 nm. We use selective reflection to resolve the Doppler-free hyperfine structure of Cesium atoms. We observed a strong modification of the reflection spectra at the presence of metamaterial and discuss the role of the spatial variation of the surface plasmon polariton on the quadrupole coupling.Comment: 6 pages, 5 figure

Electron Spin Relaxation of Cu_A and Cytochrome a in Cytochrome c Oxidase. Comparison to heme, copper, and sulfur radical complexes

The method of continuous saturation has been used to measure the electron spin relaxation parameter T_(1)T_(2) at temperatures between 10 and 50 K for a variety of S = 1/2 species including: Cu_A and cytochrome a of cytochrome c oxidase, the type 1 copper in several blue copper proteins, the type 2 copper in laccase, inorganic Cu(II) complexes, sulfur radicals, and low spin heme proteins. The temperature dependence and the magnitude of T_(1)T_(2) for all of the species examined are accounted for by assuming that the Van Vleck Raman process dominates the electron spin-lattice relaxation. Over the entire temperature range examined, the relaxation of the type 1 coppers in six to seven times faster than that of type 2 copper, inorganic copper, and sulfur radicals, in spite of the similar g-anisotropies of these species. This result may indicate that the coupling of the phonon bath to the spin center is more effective in type 1 coppers than in the other complexes studied. The relaxation of Cu_A of cytochrome oxidase exhibits an unusual temperature dependence relative to the other copper complexes studied, suggesting that the protein environment of this center is different from that of the other copper centers studied and/or that Cu_A is influenced by a magnetic dipolar interaction with another, faster-relaxing paramagnetic site in the enzyme. A comparison of the saturation characteristics of the Cu_A EPR signal in native and partially reduced CO complexes of the enzyme also suggests the existence of such an interaction. The implications of these results with respect to the disposition of the metal centers in cytochrome oxidase are discusse

Tryptophan- and arginine-rich antimicrobial peptides: Structures and mechanisms of action

AbstractAntimicrobial peptides encompass a number of different classes, including those that are rich in a particular amino acid. An important subset are peptides rich in Arg and Trp residues, such as indolicidin and tritrpticin, that have broad and potent antimicrobial activity. The importance of these two amino acids for antimicrobial activity was highlighted through the screening of a complete combinatorial library of hexapeptides. These residues possess some crucial chemical properties that make them suitable components of antimicrobial peptides. Trp has a distinct preference for the interfacial region of lipid bilayers, while Arg residues endow the peptides with cationic charges and hydrogen bonding properties necessary for interaction with the abundant anionic components of bacterial membranes. In combination, these two residues are capable of participating in cation–π interactions, thereby facilitating enhanced peptide–membrane interactions. Trp sidechains are also implicated in peptide and protein folding in aqueous solution, where they contribute by maintaining native and nonnative hydrophobic contacts. This has been observed for the antimicrobial peptide from human lactoferrin, possibly restraining the peptide structure in a suitable conformation to interact with the bacterial membrane. These unique properties make the Arg- and Trp-rich antimicrobial peptides highly active even at very short peptide lengths. Moreover, they lead to structures for membrane-mimetic bound peptides that go far beyond regular α-helices and β-sheet structures. In this review, the structures of a number of different Trp- and Arg-rich antimicrobial peptides are examined and some of the major mechanistic studies are presented

Correcting datasets leads to more homogeneous early-twentieth-century sea surface warming

Existing estimates of sea surface temperatures (SSTs) indicate that, during the early twentieth century, the North Atlantic and northeast Pacific oceans warmed by twice the global average, whereas the northwest Pacific Ocean cooled by an amount equal to the global average1,2,3,4. Such a heterogeneous pattern suggests first-order contributions from regional variations in forcing or in ocean–atmosphere heat fluxes5,6. These older SST estimates are, however, derived from measurements of water temperatures in ship-board buckets, and must be corrected for substantial biases7,8,9. Here we show that correcting for offsets among groups of bucket measurements leads to SST variations that correlate better with nearby land temperatures and are more homogeneous in their pattern of warming. Offsets are identified by systematically comparing nearby SST observations among different groups10. Correcting for offsets in German measurements decreases warming rates in the North Atlantic, whereas correcting for Japanese measurement offsets leads to increased and more uniform warming in the North Pacific. Japanese measurement offsets in the 1930s primarily result from records having been truncated to whole degrees Celsius when the records were digitized in the 1960s. These findings underscore the fact that historical SST records reflect both physical and social dimensions in data collection, and suggest that further opportunities exist for improving the accuracy of historical SST records9,11