Metabolic cardioprotection: new concepts in implementation of cardioprotective effects of meldonium

Recent studies confirm the need to find means to correct ischemic / reperfusion injury due to the hemodynamic medicine, which are already known do not have the proper cardioprotective effects. Key issue is the possibility of drug effects on the mitochondria of cardiomyocytes that controls the aerobic metabolism and maintenance of ATP admission into cardiomyocyte

Study of dose-dependent effect of 2-ethyl-6-methyl-3 hydroxypyridine succinate on the contractile function of isolated rat heat

In experiments on the isolated rat heart there were studied the effects of different doses (21.43 mg/kg/day and 85 . 72 mg/kg/day) 2-ethyl-6-methyl-3 hydroxypy ridine succinate ("EkoPharmInvest", Russia), on the contractile function of isolated hearts subjected to prior doxorubicin model (20 mg/kg, intraperitoneal) of pathology. The dynamic of the power mechanisms of ion transport was evaluated by imposing high h eart rate (480 BPM) and increase concentration of Са2+ to 5 mmol in perfusat

Human Tra2 proteins jointly control a CHEK1 splicing switch among alternative and constitutive target exons

Alternative splicing—the production of multiple messenger RNA isoforms from a single gene—is regulated in part by RNA binding proteins. While the RBPs transformer2 alpha (Tra2α) and Tra2β have both been implicated in the regulation of alternative splicing, their relative contributions to this process are not well understood. Here we find simultaneous—but not individual—depletion of Tra2α and Tra2β induces substantial shifts in splicing of endogenous Tra2β target exons, and that both constitutive and alternative target exons are under dual Tra2α–Tra2β control. Target exons are enriched in genes associated with chromosome biology including CHEK1, which encodes a key DNA damage response protein. Dual Tra2 protein depletion reduces expression of full-length CHK1 protein, results in the accumulation of the DNA damage marker γH2AX and decreased cell viability. We conclude Tra2 proteins jointly control constitutive and alternative splicing patterns via paralog compensation to control pathways essential to the maintenance of cell viability

Physical properties of thermoelectric zinc antimonide using first-principles calculations

We report first principles calculations of the structural, electronic, elastic and vibrational properties of the semiconducting orthorhombic ZnSb compound. We study also the intrinsic point defects in order to eventually improve the thermoelectric properties of this already very promising thermoelectric material. Concerning the electronic properties, in addition to the band structure, we show that the Zn (Sb) crystallographically equivalent atoms are not exactly equivalent from the electronic point of view. Lattice dynamics, elastic and thermodynamic properties are found to be in good agreement with experiments and they confirm the non equivalency of the zinc and antimony atoms from the vibrational point of view. The calculated elastic properties show a relatively weak anisotropy and the hardest direction is the y direction. We observe the presence of low energy modes involving both Zn and Sb atoms at about 5-6 meV, similarly to what has been found in Zn4Sb3 and we suggest that the interactions of these modes with acoustic phonons could explain the relatively low thermal conductivity of ZnSb. Zinc vacancies are the most stable defects and this explains the intrinsic p-type conductivity of ZnSb.Comment: 33 pages, 8 figure

The near-infrared detection of PSR B0540-69 and its nebula

The ~1700 year old PSR B0540-69 in the LMC is considered the twin of the Crab pulsar because of its similar spin parameters, magnetic field, and energetics. Its optical spectrum is fit by a power-law, ascribed to synchrotron radiation, like for the young Crab and Vela pulsars. nIR observations, never performed for PSR B0540-69, are crucial to determine whether the optical power-law spectrum extends to longer wavelengths or a new break occurs, like it happens for both the Crab and Vela pulsars in the mIR, hinting at an even more complex particle energy and density distribution in the pulsar magnetosphere. We observed PSR B0540-69 in the J, H, and Ks bands with the VLT to detect it, for the first time, in the nIR and characterise its optical-to-nIR spectrum. To disentangle the pulsar emission from that of its pulsar wind nebula (PWN), we obtained high-spatial resolution adaptive optics images with NACO. We could clearly identify PSR B0540-69 in our J, H, and Ks-band images and measure its flux (J=20.14, H=19.33, Ks=18.55, with an overall error of +/- 0.1 magnitudes in each band). The joint fit to the available optical and nIR photometry with a power-law spectrum gives a spectral index alpha=0.70 +/-0.04. The comparison between our NACO images and HST optical ones does not reveal any apparent difference in the PWN morphology as a function of wavelength. The PWN optical-to-nIR spectrum is also fit by a single power-law, with spectral index alpha=0.56+/- 0.03, slightly flatter than the pulsar's. Using NACO at the VLT, we obtained the first detection of PSR B0540-69 and its PWN in the nIR. Due to the small angular scale of the PWN (~4") only the spatial resolution of the JWST will make it possible to extend the study of the pulsar and PWN spectrum towards the mid-IR.Comment: 11 pages, 10 figures, Accepted for publication on Astronomy and Astrophysic

Impact of oral melatonin on the electroretinogram cone response

<p>Abstract</p> <p>Background</p> <p>In the eye, melatonin plays a role in promoting light sensitivity at night and modulating many aspects of circadian retinal physiology. It is also an inhibitor of retinal dopamine, which is a promoter of day vision through the cone system. Consequently, it is possible that oral melatonin (an inhibitor of retinal dopamine) taken to alleviate circadian disorders may affect cone functioning. Our aim was to assess the impact of melatonin on the cone response of the human retina using electroretinography (ERG).</p> <p>Methods</p> <p>Twelve healthy participants aged between 18 to 52 years old were submitted to a placebo-controlled, double-blind, crossover, and counterbalanced-order design. The subjects were tested on 2 sessions beginning first with a baseline ERG, followed by the administration of the placebo or melatonin condition and then, 30 min later, a second ERG to test the effect.</p> <p>Results</p> <p>Following oral melatonin administration, a significant decrease of about 8% of the cone maximal response was observed (mean 6.9 μV ± SEM 2.0; P = 0.0065) along with a prolonged b-wave implicit time of 0.4 ms ± 0.1, 50 minutes after ingestion.</p> <p>Conclusion</p> <p>Oral melatonin appears to reach the eye through the circulation. When it is administered at a time of day when it is not usually present, melatonin appears to reduce input to retinal cones. We believe that the impact of melatonin on retinal function should be taken into consideration when used without supervision in chronic self-medication for sleep or circadian disorder treatment.</p

Uniparental Genetic Heritage of Belarusians: Encounter of Rare Middle Eastern Matrilineages with a Central European Mitochondrial DNA Pool

Ethnic Belarusians make up more than 80% of the nine and half million people inhabiting the Republic of Belarus. Belarusians together with Ukrainians and Russians represent the East Slavic linguistic group, largest both in numbers and territory, inhabiting East Europe alongside Baltic-, Finno-Permic- and Turkic-speaking people. Till date, only a limited number of low resolution genetic studies have been performed on this population. Therefore, with the phylogeographic analysis of 565 Y-chromosomes and 267 mitochondrial DNAs from six well covered geographic sub-regions of Belarus we strove to complement the existing genetic profile of eastern Europeans. Our results reveal that around 80% of the paternal Belarusian gene pool is composed of R1a, I2a and N1c Y-chromosome haplogroups – a profile which is very similar to the two other eastern European populations – Ukrainians and Russians. The maternal Belarusian gene pool encompasses a full range of West Eurasian haplogroups and agrees well with the genetic structure of central-east European populations. Our data attest that latitudinal gradients characterize the variation of the uniparentally transmitted gene pools of modern Belarusians. In particular, the Y-chromosome reflects movements of people in central-east Europe, starting probably as early as the beginning of the Holocene. Furthermore, the matrilineal legacy of Belarusians retains two rare mitochondrial DNA haplogroups, N1a3 and N3, whose phylogeographies were explored in detail after de novo sequencing of 20 and 13 complete mitogenomes, respectively, from all over Eurasia. Our phylogeographic analyses reveal that two mitochondrial DNA lineages, N3 and N1a3, both of Middle Eastern origin, might mark distinct events of matrilineal gene flow to Europe: during the mid-Holocene period and around the Pleistocene-Holocene transition, respectively

Possible optical counterpart of PSR J1357-6429

(Abridged) PSR J1357-6429 is a Vela-like radio pulsar that has been recently detected in X-rays and gamma-rays. It powers a compact tail-like X-ray pulsar wind nebula and X-ray-radio plerion associated with an extended TeV source HESS J1356-645. We present our deep optical observations with the Very Large Telescope to search for an optical counterpart of the pulsar and its nebula. We detect a point-like source in V, R, and I bands whose position is within the 1-sigma error circle of the X-ray position of the pulsar, and whose colours are distinct from those of ordinary stars. We consider it as a candidate optical counterpart of the pulsar. If it is indeed the counterpart, its 5-sigma offset from the radio pulsar position, measured about 9 yr earlier, implies that the transverse velocity of the pulsar is in the range of 1600--2000 km s^{-1} at the distance of 2--2.5 kpc, making it the fastest moving pulsar known. The direction of the estimated proper motion coincides with the extension of the pulsar's X-ray tail, suggesting that this is a jet. The tentative optical luminosity and efficiency of the pulsar are similar to those of the Vela pulsar, which also supports the optical identification. However, the candidate undergoes an unusually steep dereddened flux increase towards the infrared with a spectral index of about 5, that is not typical of optical pulsars. It implies a strong double-knee spectral break in the pulsar emission between the optical and X-rays. The reasons for the spectral steepness are unclear. It may be caused by a nebula knot projected onto the jet and strongly overlapping with the pulsar, as observed for the Crab, where the knot has a significantly steeper spectrum than the pulsar. We find no other signs of the pulsar nebula in the optical. Alternatively, the detected source may be a faint AGN, that has not yet been seen at other wavelengths.Comment: 13 pages, 10 figures, 4 table