Downregulation of Serotonergic Gene Expression in the Raphe Nuclei of the Midbrain Under Chronic Social Defeat Stress in Male Mice

There is ample experimental evidence supporting the hypothesis that the brain serotonergic system is involved in the control of chronic social defeat stress (CSDS), depression, and anxiety. The study aimed to analyze mRNA levels of the serotonergic genes in the raphe nuclei of midbrain that may be associated with chronic social defeats consistently shown by male mice in special experimental settings. The serotonergic genes were the Tph2, Sert, Maoa, and Htr1a. The Bdnf and Creb genes were also studied. The experimental groups were composed of male mice with experience of defeats in 21 daily encounters and male mice with the same track record of defeats followed by a no-defeat period without agonistic interactions (relative rest for 14 days). It has been shown that mRNA levels of the Tph2, Maoa, Sert, Htr1a, Bdnf, and Creb genes in the raphe nuclei of defeated mice are decreased as compared with the controls. The expression of the serotonergic genes as well as the Creb gene is not restored to the control level after the 2 weeks of relative rest. mRNA levels of Bdnf gene are not recovered to the control levels, although some upregulation was observed in rested losers. CSDS experience inducing the development of mixed anxiety/depression-like state in male mice downregulates the expression of serotonergic genes associated with the synthesis, inactivation, and reception of serotonin. The Bdnf and Creb genes in the midbrain raphe nuclei are also downregulated under CSDS. Period of relative rest is not enough for most serotonergic genes to recover expression to the control levels.     

Structural and energetic determinants of primary proton transfer in bacteriorhodopsin.

In the light-driven bacteriorhodopsin proton pump, the first proton transfer step is from the retinal Schiff base to a nearby carboxylate group. The mechanism of this transfer step is highly controversial, in particular whether a direct proton jump is allowed. Here, we review the structural and energetic determinants of the direct proton transfer path computed by using a combined quantum mechanical/molecular mechanical approach. Both protein flexibility and electrostatic interactions play an important role in shaping the proton transfer energy profile. Detailed analysis of the energetics of putative transitions in the first half of the photocycle focuses on two elements that determine the likelihood that a given configuration of the active site is populated during the proton-pumping cycle. First, the rate-limiting barrier for proton transfer must be consistent with the kinetics of the photocycle. Second, the active-site configuration must be compatible with a productive overall pumping cycle.     

Cationic screening of charged surface groups (carboxylates) affects electron transfer steps in photosystem-II water oxidation and quinone reduction

The functional or regulatory role of long-distance interactions between protein surface and interior represents an insufficiently understood aspect of protein function. Cationic screening of surface charges determines the morphology of thylakoid membrane stacks. We show that it also influences directly the light-driven reactions in the interior of photosystem II (PSII). After laser-flash excitation of PSII membrane particles from spinach, time courses of the delayed recombination fluorescence (10 μs–10 ms) and the variable chlorophyll-fluorescence yield (100 μs–1 s) were recorded in the presence of chloride salts. At low salt-concentrations, a stimulating effect was observed for the S-state transition efficiency, the time constant of O₂-formation at the Mn₄Ca-complex of PSII, and the halftime of re-oxidation of the primary quinone acceptor (Q_a) by the secondary quinone acceptor (Q_b). The cation valence determined the half-effect concentrations of the stimulating salt effect, which were around 6 μM, 200 μM and 10 mM for trivalent (LaCl₃), bivalent (MgCl₂, CaCl₂), and monovalent cations (NaCl, KCl), respectively. A depressing high-salt effect also depended strongly on the cation valence (onset concentrations around 2 mM, 50 mM, and 500 mM). These salt effects are proposed to originate from electrostatic screening of negatively charged carboxylate sidechains, which are found in the form of carboxylate clusters at the solvent-exposed protein surface. We conclude that the influence of electrostatic screening by solvent cations manifests a functionally relevant long-distance interaction between protein surface and electron-transfer reactions in the protein interior. A relation to regulation and adaptation in response to environmental changes is conceivable.     

Stimulation of luminescence of mycelium of luminous fungus Neonothopanus nambi by ionizing radiation

The luminescent system of higher luminous fungi is not fully understood and the enzyme/substrate pair of the light emission reaction has not been isolated. It was suggested that luminescence of fungi involves oxidase‐type enzymes, and reactive oxygen species are important for fungal light production. Generation of reactive oxygen species can be stimulated by ionizing irradiation, which has not been studied for luminous fungi. We report the effect of X‐irradiation on the luminescence of fungus Neonothopanus nambi. Experiments were performed with mycelium on a home‐built setup based on an X‐ray tube and monochromator/photomultiplier tube. Application of X‐rays does not change the emission spectrum, but after approximately 20 min of continuous irradiation, light production from unsupported mycelium starts growing and increases up to approximately five times. After peaking, its level decreases irrespective of the presence of X‐irradiation. After staying at a certain level, light production collapses to zero, which is not related to the drying of the mycelium or thermal impact of radiation. The observed shape of kinetics is characteristic of a multistage and/or chain reaction. The time profile of light production must reflect the current levels of radicals present in the system and/or the activity of enzyme complexes involved in light production. Copyright © 2014 John Wiley & Sons, Ltd.     

Genetic relationships of Chukchi charr <Emphasis Type="Italic">Salvelinus andriashevi</Emphasis> and Taranetz charr <Emphasis Type="Italic">Salvelinus taranetzi</Emphasis>

On the basis of sequence analysis of the mitochondrial DNA (mtDNA) control region (CR), cytochrome b (Cytb), and cytochrome oxidase-1 (CoI) genes, the relationships of endemic species Salvelinus andriashevi Berg, 1948, represented by the only population from Lake Estikhed (Chukotka), were estimated. The data on the genealogical analysis of mtDNA haplotypes supported phylogenetic closeness of S. andriashevi and S. taranetzi. It was also demonstrated that the specimens of Chukchi charr, along with Salvelinus sp. 4 (Lake Nachikinskoe), S. krogiusae (Lake Dal’nee), S. boganidae and S. elgyticus (Lake El’gygytgyn), and S. a. erythrinus from Canada’s Northwest Territories (NWT) belonged to the Arctic group of Taranetz charr. The problem of coincidence of taxonomic differentiation of charrs of the genus Salvelinus based on morphological and genetic analyses is discussed.     

On the inhibition of muscle membrane chloride conductance by aromatic carboxylic acids

25 aromatic carboxylic acids which are analogs of benzoic acid were tested in the rat diaphragm preparation for effects on chloride conductance (G(Cl)). Of the 25, 19 were shown to reduce membrane G(Cl) with little effect on other membrane parameters, although their apparent K(i) varied widely. This inhibition was reversible if exposure times were not prolonged. The most effective analog studied was anthracene-9-COOH (9-AC; K(i) = 1.1 x 10(-5) M). Active analogs produced concentration-dependent inhibition of a type consistent with interaction at a single site or group of sites having similar binding affinities, although a correlation could also be shown between lipophilicity and K(i). Structure-activity analysis indicated that hydrophobic ring substitution usually increased inhibitory activity while para polar substitutions reduced effectiveness.

These compounds do not appear to inhibit G(Cl) by altering membrane surface charge and the inhibition produced is not voltage dependent. Qualitative characteristics of the I-V relationship for Cl(-) current are not altered. Conductance to all anions is not uniformly altered by these acids as would be expected from steric occlusion of a common channel. Concentrations of 9-AC reducing G(Cl) by more than 90 percent resulted in slight augmentation of G(I). The complete conductance sequence obtained at high levels of 9-AC was the reverse of that obtained under control conditions. Permeability sequences underwent progressive changes with increasing 9-AC concentration and ultimately inverted at high levels of the analog. Aromatic carboxylic acids appear to inhibit G(Cl) by binding to a specific intramembrane site and altering the selectivity sequence of the membrane anion channel.

     

New methods of X-ray surgical diagnosis and treatment of varicocele in children and adolescents

The authors studied 520 patients with left-sided varicocele by left-sided phleborenotesticulography of Doppler ultrasonography, tensiometry of the left renotesticular venous system, blood gas composition, hormonal parameters, and etc. They present rationale for and evidence illustrations of aortomesenteric compression of the left renal vein, left-sided phleborenal hypertension prior to and after surgery for endovascular occlusion of the left testicular vein, before and following intervenous proximal testiculoiliac venous bypass surgery. The data of andrological dysfunction in patients with varicosis of the pampiniform plexus and spermatic cord (varicocele) are presented. An algorithm of examination and treatment of this cohort of patients, by using both miniinvasive techniques (for X-ray endovascular occlusion of the temporal veins under local anesthesia) and high tech operations using microsurgical techniques (testiculoiliac venous anastomosis), is outlined.