The endocannabinoid/cannabinoid receptor 2 system protects against cisplatin-induced hearing loss

Previous studies have demonstrated the presence of cannabinoid 2 receptor (CB2R) in the rat cochlea which was induced by cisplatin. In an organ of Corti-derived cell culture model, it was also shown that an agonist of the CB2R protected these cells against cisplatin-induced apoptosis. In the current study, we determined the distribution of CB2R in the mouse and rat cochleae and examined whether these receptors provide protection against cisplatin-induced hearing loss. In a knock-in mouse model expressing the CB2R tagged with green fluorescent protein, we show distribution of CB2R in the organ of Corti, stria vascularis, spiral ligament and spiral ganglion cells. A similar distribution of CB2R was observed in the rat cochlea using a polyclonal antibody against CB2R. Trans-tympanic administration of (2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone (JWH015), a selective agonist of the CB2R, protected against cisplatin-induced hearing loss which was reversed by blockade of this receptor with 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone (AM630), an antagonist of CB2R. JWH015 also reduced the loss of outer hair cells (OHCs) in the organ of Corti, loss of inner hair cell (IHC) ribbon synapses and loss of Na+/K+-ATPase immunoreactivity in the stria vascularis. Administration of AM630 alone produced significant hearing loss (measured by auditory brainstem responses) which was not associated with loss of OHCs, but led to reductions in the levels of IHC ribbon synapses and strial Na+/K+-ATPase immunoreactivity. Furthermore, knock-down of CB2R by trans-tympanic administration of siRNA sensitized the cochlea to cisplatin-induced hearing loss at the low and middle frequencies. Hearing loss induced by cisplatin and AM630 in the rat was associated with increased expression of genes for oxidative stress and inflammatory proteins in the rat cochlea. In vitro studies indicate that JWH015 did not alter cisplatin-induced killing of cancer cells suggesting this agent could be safely used during cisplatin chemotherapy. These data unmask a protective role of the cochlear endocannabinoid/CB2R system which appears tonically active under normal conditions to preserve normal hearing. However, an exogenous agonist is needed to boost the activity of endocannabinoid/CB2R system for protection against a more traumatic cochlear insult, as observed with cisplatin administration.</p

ALMA imaging of SDP.81 - I. A pixelated reconstruction of the far-infrared continuum emission

We present a sub-50 pc-scale analysis of the gravitational lens system SDP.81 at redshift 3.042 using Atacama Large Millimetre/submillimetre Array (ALMA) science verification data. We model both the mass distribution of the gravitational lensing galaxy and the pixelated surface brightness distribution of the background source using a novel Bayesian technique that fits the data directly in visibility space. We find the 1 and 1.3 mm dust emission to be magnified by a factor of u_tot = 17.6+/-0.4, giving an intrinsic total star-formation rate of 315+/-60 M_sol/yr and a dust mass of 6.4+/-1.5*10^8 M_sol. The reconstructed dust emission is found to be non-uniform, but composed of multiple regions that are heated by both diffuse and strongly clumped star-formation. The highest surface brightness region is a ~1.9*0.7 kpc disk-like structure, whose small extent is consistent with a potential size-bias in gravitationally lensed starbursts. Although surrounded by extended star formation, with a density of 20-30+/-10 M_sol/yr/kpc^2, the disk contains three compact regions with densities that peak between 120-190+/-20 M_sol/yr/kpc^2. Such star-formation rate densities are below what is expected for Eddington-limited star-formation by a radiation pressure supported starburst. There is also a tentative variation in the spectral slope of the different star-forming regions, which is likely due to a change in the dust temperature and/or opacity across the source.Comment: MNRAS accepted 2015 April 1

ALMA imaging of SDP.81 - II. A pixelated reconstruction of the CO emission lines

We present a sub-100 pc-scale analysis of the CO molecular gas emission and kinematics of the gravitational lens system SDP.81 at redshift 3.042 using Atacama Large Millimetre/submillimetre Array (ALMA) science verification data and a visibility-plane lens reconstruction technique. We find clear evidence for an excitation dependent structure in the unlensed molecular gas distribution, with emission in CO (5-4) being significantly more diffuse and structured than in CO (8-7). The intrinsic line luminosity ratio is r_8-7/5-4 = 0.30 +/- 0.04, which is consistent with other low-excitation starbursts at z ~ 3. An analysis of the velocity fields shows evidence for a star-forming disk with multiple velocity components that is consistent with a merger/post-coalescence merger scenario, and a dynamical mass of M(< 1.56 kpc) = 1.6 +/- 0.6 x 10^10 M_sol . Source reconstructions from ALMA and the Hubble Space Telescope show that the stellar component is offset from the molecular gas and dust components. Together with Karl G. Jansky Very Large Array CO (1-0) data, they provide corroborative evidence for a complex ~2 kpc-scale starburst that is embedded within a larger ~15 kpc structure.Comment: MNRAS accepted, 6th July 201

Engineering method of determination of potential energy of deformation of the spatially loaded flat frames of difficult geometrical form

В даній роботі запропоновано ефективну інженерну методику розрахунку плоских просторово навантажених конструкцій рам сільськогосподарських машин з загином поздовжніх лонжеронів. При дослідженні напружено - деформованого стану даного типу конструкцій найбільш ефективним є застосування методу мінімуму потенціальної енергії . В роботі запропоновано методику знаходження потенціальної енергії деформації для випадку, якщо просторова рама включає конструктивні елементи складної геометричної форми.In-process this the effective engineering method of calculation of the flat spatially loaded constructions of frames of agricultural machines is offered with the bend of longitudinal longerons. At research tensely - the deformed state of this type of constructions, application of method of minimum of potential energy is most effective . The method of finding of potential energy of deformation is in-process offered for a case if a spatial frame includes the structural elements of difficult geometrical form

Colonization With Staphylococcus aureus in Atopic Dermatitis Patients: Attempts to Reveal the Unknown

Atopic dermatitis (AD) patients are massively colonized with Staphylococcus aureus (S. aureus) in lesional and non-lesional skin. A skin infection may become systemic if left untreated. Of interest, the incidence of multi-drug resistant S. aureus (MRSA) in AD patients is higher as compared to a healthy population, which makes treatment even more challenging. Information on the specific genetic background of S. aureus accompanying and/or causing AD flares would be of great importance in terms of possible treatment option development. In this review, we summarized the data on the prevalence of S. aureus in general in AD skin, and the prevalence of specific clones that might be associated with flares of eczema. We put our special interest in the presence and role of staphylococcal enterotoxins as important virulence factors in the epidemiology of AD-derived S. aureus. Also, we summarize the present and potentially useful future anti-staphylococcal treatment

Research model robot-hexapod under static and dynamic loads

In the paper the stress-strain state of hexapod robot is considered in order to clarify its dynamical characteristics. Full-size model of hexapod robot is built in the SolidWorks program complex. The state of the robot was analyzed in an extremely dangerous location at static loading. Dynamic analysis was conducted to clarify oscillation of the support unit in the robot’s construction. The results of the survey show that such robot design cannot be used in the environments with the vibrating background below 5 Hz