PV1 is a key structural component for the formation of the stomatal and fenestral diaphragms

PV1 is an endothelial-specific integral membrane glycoprotein associated with the stomatal diaphragms of caveolae, transendothelial channels, and vesiculo-vacuolar organelles and the diaphragms of endothelial fenestrae. Multiple PV1 homodimers are found within each stomatal and fenestral diaphragm. We investigated the function of PV1 within these diaphragms and their regulation and found that treatment of endothelial cells in culture with phorbol myristate acetate (PMA) led to upregulation of PV1. This correlated with de novo formation of stomatal diaphragms of caveolae and transendothelial channels as well as fenestrae upon PMA treatment. The newly formed diaphragms could be labeled with anti-PV1 antibodies. The upregulation of PV1 and formation of stomatal and fenestral diaphragms by PMA was endothelium specific and was the highest in microvascular endothelial cells compared with their large vessel counterparts. By using a siRNA approach, PV1 mRNA silencing prevented the de novo formation of the diaphragms of caveolae as well as fenestrae and transendothelial channels. Overexpression of PV1 in endothelial cells as well as in cell types that do not harbor caveolar diaphragms in situ induced de novo formation of caveolar stomatal diaphragms. Lastly, PV1 upregulation by PMA required the activation of Erk1/2 MAP kinase pathway and was protein kinase C independent. Taken together, these data show that PV1 is a key structural component, necessary for the biogenesis of the stomatal and fenestral diaphragms.     

Characteristic Features of EEG Spectral Characteristics in Persons with Deviant Sexual Behavior

The study was performed with participation of 59 right-handed men. The normal group consisted of 19 subjects, and 40 patients with organic brain lesions who had commited sexual offenses were divided into two groups: 19 patients with a diagnosis of paraphilia (pathology of sexual drive) made up the main test group, and 21 patients without such a diagnosis formed the control group. A monopolar EEG was recorded in 16 standard leads in the states of rest (eyes closed) and general activation (eyes open) and during presentation of cognitive tests. The following EEG features manifest in all the frequency ranges and functional states were revealed in the group of patients with paraphilias as compared to the control groups: a substantially increased level of interhemispheric coherence (ICoh) and increased spectral density in the posterotemporal area (T ₅, T ₆), a significantly decreased ICoh level between the F _3/4 and C _3/4 leads in the frontocentral area, and lower spectral densities in the leads Fp ₂, C ₄, and P ₄. Analysis of reactions to loads presented showed that the general arousal in the group of patients with paraphilias was characterized by significantly greater shifts of EEG parameters associated with the desynchronization reaction (as compared to the control groups) and statistically significant disorders of interhemispheric interaction and EEG reactivity in the right hemisphere in the range during performance of a visuospatial (right-hemispheric) task. The results suggest the formation of a stationary activation focus in the right hemisphere with signs of involvement of the limbic structures in patients with paraphilias.     

Synthesis and biological activity of 5-styryl and 5-phenethyl-substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles

Syntheses, biological evaluation, and structure–activity relationships for a series of novel 5-styryl and 5-phenethyl analogs of dimebolin are disclosed. The novel derivatives and dimebolin share a broad spectrum of activities against therapeutically relevant targets. Among all synthesized derivatives, 2,8-dimethyl-5-[(Z)-2-phenylvinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole and its 5-phenethyl analog are the most potent blockers of 5-HT₇, 5-HT₆, 5-HT_2C, Adrenergic α₂ and H₁ receptors. The general affinity rank order towards the studied receptors was Z-3(2) > 4(2) ? 4(3) ? dimebolin, all of them having highest affinities to 5-HT₇ receptors.     

Effect of adaptation to hypoxia on the working capacity and energy of skeletal muscles

The authors studied the working capacity and heat formation of the skeletal muscles during contraction in rats--control and those adapted to hypoxia. The force of contraction, the work and fatigueability of the muscles, as well as elevation of the muscle temperature as a result of contraction were determined under conditions of indirect muscle electrostimulation. Hypoxia adaptation failed to influence the force of muscle contraction and the work performed. However, hypoxia led to reduction of the temperature effect of the muscle contraction per unit of the work performed. This pointed to increase of the efficiency of the muscle work in hypoxia adaptation. Fatigueability of the muscles in "hypoxic" rats was elevated. Changes in the energy of the muscle contraction in hypoxia and cold adaptation were different.     

Adaptive functions of <Emphasis Type="Italic">Escherichia coli</Emphasis> polyamines in response to sublethal concentrations of antibiotics

Escherichia coli exposure to sublethal antibiotic concentrations induced an increase in cell polyamine contents. Maximum accumulation of putrescine and spermidine in response to antibiotics-induced oxidative stress preceded the increment of cadaverine, the content of which was dependent on the rpoS expression level and reached the maximum in response to fluoroquinolones. The polyamine positive modulating effects on rpoS expression increased in the following order: cadaverine-putrescine-spermidine. The reason for cadaverine accumulation was the increase in activities of lysine decarboxylases CadA and Ldc. High cadaverine accumulation in the cells exposed to fluoroquinolones and cephalosporins resulted in the reduction of porin permeability; so it was considered as a response aimed at cell protection against antibiotic penetration into the cell. Netilmycin, unlike other antibiotics, did not substantially affect the lysine decarboxylase activity and cellular polyamine pools.     

Auditory sensory support of complicated voluntary goal-aimed bimanual movements

The intrasensory and sensor-effector interactions between inter-spike intervals of acoustic stem-evoked potentials with parameters of hands coordination was found with the help of correlation analysis. Role of excitation of ascending fibres of rostral part of the pons and lateral loop in mechanisms of the auditory-motor coordination was determined. Sex-dependent differences in integration of elements of the sensor-motor system because of lateralization of incoming auditory information and complication of the motor task performed were revealed. In men, mechanisms of auditory-motor coordination have less determined character than in women. That probably determines higher level of bi-manual coordination in men. Optimal correct realization of motor program in men is performed prognostically, while in women--after a mistake has been done.     

High refractive index silicone gels for simultaneous total internal reflection fluorescence and traction force microscopy of adherent cells

Substrate rigidity profoundly impacts cellular behaviors such as migration, gene expression, and cell fate. Total Internal Reflection Fluorescence (TIRF) microscopy enables selective visualization of the dynamics of substrate adhesions, vesicle trafficking, and biochemical signaling at the cell-substrate interface. Here we apply high-refractive-index silicone gels to perform TIRF microscopy on substrates with a wide range of physiological elastic moduli and simultaneously measure traction forces exerted by cells on the substrate.     

The constant level of the right atrial pressure and its role in the venous return characteristics]

Dynamics of the central venous pressure, superior and inferior v. cava flow and venous return following action of pressor stimuli were studied in acute experiments on anaesthetised mongrel cats with artificial lung ventilation and opened chest. The central venous pressure returned to the initial level faster as compared with the dynamics of superior and inferior v. cava flow and venous return. The superior v. cava blood flow increased more than that of inferior v. cava. The data suggest that the central venous pressure is controlled near the lower constant level.