Pterin metabolism, inflammation and oxidative stress biochemical markers in schizophrenia: Factor analysis and assessment of clinical symptoms associations.

Various aspects of folate and tetrahydrobiopterin (BH4) metabolism disturbances have been detected in patients with schizophrenia.Data were obtained that disturbances in the pterins (folates and BH4) metabolism can be associated with oxidative stress and inflammation, but has not yet been confirmed in clinical studies in schizophrenia. Within the framework of this study, a correlation and factor analysis of biochemical markersof pterin metabolism, inflammation and redox imbalance in patients with schizophrenia was performed in order to test the hypothesis of the single etiopathogenetic node, including the studied biochemical processes. Methods: 125 patients with schizophrenia and 95 healthy volunteers were randomly selected and evaluated with a biochemical examination of BH4, folate, B12, homocysteine, C-reactive protein, interleukin-6, reduced glutathione levels in the blood serum; activity of superoxide dismutase and catalase - in erythrocytes; malondialdehyde - in blood plasma. All patients underwent an examination using standardized psychopathology rating scales. Spearman rank coefficient (ρ) with Benjamini-Hochberg correction was used for the correlation analysis. The principal components analysis (PCA) was used as a factor analysis. Results: Significant correlations were found within groups of pterin metabolism, inflammatory markers and redox-imbalance, and also between separate inflammation, oxidative stress and markers of pterin metabolism. The performed factor analysis made it possible to distinguish two components: 1 - pterin metabolism, 2 - oxidativeinflammatory markers. Despite the weak statistical associations and, possibly, functional relationships between pterin metabolism and oxidative/inflammation markers, each of the components has its own clinical correlates and, probably, a separate contribution to the pathology of schizophrenia.

Single-particle and collective excitations of polar water molecules confined in nano-pores within a cordierite crystal lattice.

Recently, the low-temperature phase of water molecules confined within nanocages formed by the crystalline lattice of water-containing cordierite crystals has been reported to comprise domains with ferroelectrically ordered dipoles within the a, b-planes which are antiferroelectrically alternating along the c-axis. In the present work, comprehensive broad-band dielectric spectroscopy is combined with specific heat studies and molecular dynamics and Monte Carlo simulations in order to investigate in more detail the collective modes and single-particle excitations of nanoconfined water molecules. From DFT-MD simulations we reconstruct the potential-energy landscape experienced by the H2O molecules. A rich set of anisotropic temperature-dependent excitations is observed in the terahertz frequency range. Their origin is associated with the complex rotational/translational vibrations of confined H2O molecules. A strongly temperature dependent relaxational excitation, observed at radio-microwave frequencies for the electric field parallel to the crystallographic a-axis, E||a is analyzed in detail. The temperature dependences of loss-peak frequency and dielectric strength of the excitation together with specific heat data confirm a ferroelectric order-disorder phase transition at T0 ≈ 3 K in the network of H2O dipoles. Additional dielectric data are also provided for polarization E||b, too. Overall, these combined experimental investigations enable detailed conclusions concerning the dynamics of the confined water molecules that develop within their microscopic energy landscapes.

Homocysteine in Schizophrenia: Independent Pathogenetic Factor with Prooxidant Activity or Integral Marker of Other Biochemical Disturbances?

A wide range of studies have demonstrated that hyperhomocysteinemia is associated with the risk of schizophrenia, but currently available assumptions about the direct involvement of homocysteine (Hcy) in the pathogenesis of schizophrenia are hypothetical. It is possible that in vivo Hcy is only a marker of folate metabolism disturbances (which are involved in methylation processes) and is not a pathogenetic factor per se. Only one study has been conducted in which associations of hyperhomocysteinemia with oxidative stress in schizophrenia (oxidative damage to protein and lipids) have been found, and it has been suggested that the oxidative stress may be induced by the elevated Hcy in schizophrenic patients. But the authors did not study the level of reduced glutathione (GSH), as well as possible causes of hyperhomocysteinemia-disturbances of folate metabolism. The aim of this work is to analyze the association of Hcy levels with the following: (1) redox markers in schizophrenia GSH, markers of oxidative damage of proteins and lipids, and the activity of antioxidant enzymes in blood serum; (2) with the level of folate and cobalamin (В12); and (3) with clinical features of schizophrenia measured using the Positive and Negative Syndrome Scale (PANSS). 50 patients with schizophrenia and 36 healthy volunteers, matched by sex and age, were examined. Hcy in patients is higher than in healthy subjects (p = 0.0041), and this may be due to the lower folate level in patients (p = 0.0072). In patients, negative correlation was found between the level of Hcy both with the level of folate (ρ = -0.38, p = 0.0063) and with the level of B12 (ρ = -0.36, p = 0.0082). At the same time, patients showed higher levels of oxidative modification of serum proteins (p = 0.00046) and lower catalase (CAT) activity (p = 0.014). However, Hcy is not associated with the studied markers of oxidative stress in patients. In the group of patients with an increased level of Hcy (>10 µmol/l, n = 42) compared with other patients (n = 8), some negative symptoms (PANSS) were statistically significantly more pronounced: difficulty in abstract thinking (N5, p = 0.019), lack of spontaneity and flow in conversation (N6, p = 0.022), stereotyped thinking (N7, p = 0.013), and motor retardation (G7, p = 0.050). Thus, in patients with schizophrenia, hyperhomocysteinemia caused by deficiency of folate and B12 is confirmed and can be considered a marker of disturbances of vitamin metabolism. The redox imbalance is probably not directly related to hyperhomocysteinemia and is hypothetically caused by other pathological processes or by an indirect effect of Hcy, for example, on the enzymatic antioxidant defence system (CAT activity), which requires further exploration. Further study of the role of Hcy in the pathogenesis of schizophrenia is relevant, since the proportion of patients with hyperhomocysteinemia is high and correlations of its level with negative symptoms of schizophrenia are noted.

Dielectric ordering of water molecules arranged in a dipolar lattice.

Intermolecular hydrogen bonds impede long-range (anti-)ferroelectric order of water. We confine H2O molecules in nanosized cages formed by ions of a dielectric crystal. Arranging them in channels at a distance of ~5 Å with an interchannel separation of ~10 Å prevents the formation of hydrogen networks while electric dipole-dipole interactions remain effective. Here, we present measurements of the temperature-dependent dielectric permittivity, pyrocurrent, electric polarization and specific heat that indicate an order-disorder ferroelectric phase transition at T0 ≈ 3 K in the water dipolar lattice. Ab initio molecular dynamics and classical Monte Carlo simulations reveal that at low temperatures the water molecules form ferroelectric domains in the ab-plane that order antiferroelectrically along the channel direction. This way we achieve the long-standing goal of arranging water molecules in polar order. This is not only of high relevance in various natural systems but might open an avenue towards future applications in biocompatible nanoelectronics.

Redox chemistry in the pigment eumelanin as a function of temperature using broadband dielectric spectroscopy.

Conductive biomolecular systems are investigated for their promise of new technologies. One biomolecular material that has garnered interest for device applications is eumelanin. Its unusual properties have led to its incorporation in a wide set of platforms including transistor devices and batteries. Much of eumelanin's conductive properties are due to a solid state redox comproportionation reaction. However, most of the work that has been done to demonstrate the role of the redox chemistry in eumelanin has been via control of eumelanin's hydration content with scant attention given to temperature dependent behavior. Here we demonstrate for the first time consistency between hydration and temperature effects for the comproportionation conductivity model utilizing dielectric spectroscopy, heat capacity measurements, frequency scaling phenomena and recognizing that activation energies in the range of ∼0.5 eV correspond to proton dissociation events. Our results demonstrate that biomolecular conductivity models should account for temperature and hydration effects coherently.

Observation of dynamic charge stripes in Tm0.19Yb0.81B12 at the metal-insulator transition.

Accurate low temperature charge transport measurements in combination with high-precision x-ray diffraction experiments have allowed detection of the symmetry lowering in the single domain Tm0.19Yb0.81B12 crystals that belong to the family of dodecaborides with metal-insulator transition. Based on the fine structure analysis we discover the formation of dynamic charge stripes within the semiconducting matrix of Tm0.19Yb0.81B12. The charge dynamics in these conducting nano-size channels is characterized by broad-band optical spectroscopy that allowed estimating the frequency (~2.4 × 1011 Hz) of quantum motion of the charge carriers. It is suggested that cooperative Jahn-Teller effect in the boron sublattice is a cause of the large-amplitude rattling modes of the Tm and Yb ions responsible for the 'modulation' of the conduction band along one of the [Formula: see text] directions through the variation of 5d-2p hybridization of electron states.

Terahertz-infrared spectroscopy of Shewanella oneidensis MR-1 extracellular matrix.

Employing optical spectroscopy we have performed a comparative study of the dielectric response of extracellular matrix and filaments of electrogenic bacteria Shewanella oneidensis MR-1, cytochrome c, and bovine serum albumin. Combining infrared transmission measurements on thin layers with data of the terahertz spectra, we obtain the dielectric permittivity and AC conductivity spectra of the materials in a broad frequency band from a few cm-1 up to 7000 cm-1 in the temperature range from 5 to 300 K. Strong absorption bands are observed in the three materials that cover the range from 10 to 300 cm-1 and mainly determine the terahertz absorption. When cooled down to liquid helium temperatures, the bands in Shewanella oneidensis MR-1 and cytochrome c reveal a distinct fine structure. In all three materials, we identify the presence of liquid bound water in the form of librational and translational absorption bands at ≈ 200 and ≈ 600 cm-1, respectively. The sharp excitations seen above 1000 cm-1 are assigned to intramolecular vibrations.

Observation of dielectric universalities in albumin, cytochrome C and Shewanella oneidensis MR-1 extracellular matrix.

The electrodynamics of metals is well understood within the Drude conductivity model; properties of insulators and semiconductors are governed by a gap in the electronic states. But there is a great variety of disordered materials that do not fall in these categories and still respond to external field in an amazingly uniform manner. At radiofrequencies delocalized charges yield a frequency-independent conductivity σ 1(ν) whose magnitude exponentially decreases while cooling. With increasing frequency, dispersionless conductivity starts to reveal a power-law dependence σ 1(ν)∝ν s with s < 1 caused by hopping charge carriers. At low temperatures, such Universal Dielectric Response can cross over to another universal regime with nearly constant loss ε″∝σ1/ν = const. The powerful research potential based on such universalities is widely used in condensed matter physics. Here we study the broad-band (1-1012 Hz) dielectric response of Shewanella oneidensis MR-1 extracellular matrix, cytochrome C and serum albumin. Applying concepts of condensed matter physics, we identify transport mechanisms and a number of energy, time, frequency, spatial and temperature scales in these biological objects, which can provide us with deeper insight into the protein dynamics.

Vibrational states of nano-confined water molecules in beryl investigated by first-principles calculations and optical experiments.

Using quantum mechanical calculations within density functional theory, we provide a comprehensive analysis of infrared-active excitation of water molecules confined in nanocages of a beryl crystal lattice. We calculate infrared-active modes including the translational, librational, and mixed-type resonances of regular and heavy water molecules. The results are compared to the experimental spectra measured for the two principal polarizations of the electric field: parallel and perpendicular to the crystallographic c-axis. Good agreement is achieved between calculated and measured isotopic shifts of the normal modes. We analyze the vibrational modes in connection with the structural characteristics and arrangements of water molecules within the beryl crystal. Specific atomic displacements are assigned to each experimentally detected vibrational mode resolving the properties of nano-confined water on scales not accessible by experiments. Our results elucidate the applicability and efficiency of a combined experimental and computational approach for describing and an in-depth understanding of nano-confined water, and pave the way for future studies of more complex systems.

Dielectric properties of semi-insulating Fe-doped InP in the terahertz spectral region.

We report the values and the spectral dependence of the real and imaginary parts of the dielectric permittivity of semi-insulating Fe-doped InP crystalline wafers in the 2-700 cm-1 (0.06-21 THz) spectral region at room temperature. The data shows a number of absorption bands that are assigned to one- and two-phonon and impurity-related absorption processes. Unlike the previous studies of undoped or low-doped InP material, our data unveil the dielectric properties of InP that are not screened by strong free-carrier absorption and will be useful for designing a wide variety of InP-based electronic and photonic devices operating in the terahertz spectral range.

Terahertz-infrared electrodynamics of single-wall carbon nanotube films.

Broad-band (4-20 000 cm-1) spectra of real and imaginary conductance of a set of high-quality pristine and AuCl3-doped single-walled carbon nanotube (SWCNT) films with different transparency are systematically measured. It is shown that while the high-energy (≥1 eV) response is determined by well-known interband transitions, the lower-energy electrodynamic properties of the films are fully dominated by unbound charge carriers. Their main spectral effect is seen as the free-carrier Drude-type contribution. Partial localization of these carriers leads to a weak plasmon resonance around 100 cm-1. At the lowest frequencies, below 10 cm-1, a gap-like feature is detected whose origin is associated with the energy barrier experienced by the carriers at the intersections between SWCNTs. It is assumed that these three mechanisms are universal and determine the low-frequency terahertz-infrared electrodynamics of SWCNT wafer-scale films.

Incipient ferroelectricity of water molecules confined to nano-channels of beryl.

Water is characterized by large molecular electric dipole moments and strong interactions between molecules; however, hydrogen bonds screen the dipole-dipole coupling and suppress the ferroelectric order. The situation changes drastically when water is confined: in this case ordering of the molecular dipoles has been predicted, but never unambiguously detected experimentally. In the present study we place separate H2O molecules in the structural channels of a beryl single crystal so that they are located far enough to prevent hydrogen bonding, but close enough to keep the dipole-dipole interaction, resulting in incipient ferroelectricity in the water molecular subsystem. We observe a ferroelectric soft mode that causes Curie-Weiss behaviour of the static permittivity, which saturates below 10 K due to quantum fluctuations. The ferroelectricity of water molecules may play a key role in the functioning of biological systems and find applications in fuel and memory cells, light emitters and other nanoscale electronic devices.