Study of the Oxolin antiviral drug effect for the improvement of potato seed material during in vitro cultivation

The article presents an analysis of the potato breeding problems in Russia which are associated with the low phytosanitary state of potato seed material infected with viral and bacterial diseases, as a result, it is necessary to carry out its improvement and the use of Russian varieties. Experiments were conducted in the laboratory of plant microclonal propagation according to the methodological recommendations for improvement and accelerated propagation of seed potatoes. The results of research on refining the technology of seed potato improvement by adding the Oxolin antiviral drug to the standard nutrient medium MS; its optimal concentrations for obtaining the largest number of uninfected plants of the studied varieties were identified. For potato varieties Liga, Hussar, and Real, the optimal concentration was 20 mg/l of Oxolin, while in the varieties Aurora, Real, and Sirenevy tuman, the concentration was 30 mg/l. Therefore, it is necessary to search for antiviral drugs with an alternative mechanism of action which remains very relevant and practically significant. The research results obtained in this work can be applied both to optimize the cultivation regime of potato microclones in vitro and to enhance the productive process of the uninfected microplants

Critical association of ncRNA with introns

It has been widely acknowledged that non-coding RNAs are master-regulators of genomic functions. However, the significance of the presence of ncRNA within introns has not received proper attention. ncRNA within introns are commonly produced through the post-splicing process and are specific signals of gene transcription events, impacting many other genes and modulating their expression. This study, along with the following discussion, details the association of thousands of ncRNAs—snoRNA, miRNA, siRNA, piRNA and long ncRNA—within human introns. We propose that such an association between human introns and ncRNAs has a pronounced synergistic effect with important implications for fine-tuning gene expression patterns across the entire genome

Down-regulation of the transcription factor snail in the placentas of patients with preeclampsia and in a rat model of preeclampsia

<p>Abstract</p> <p>Background</p> <p>Placental malfunction in preeclampsia is believed to be a consequence of aberrant differentiation of trophoblast lineages and changes in utero-placental oxygenation. The transcription factor Snail, a master regulator molecule of epithelial-mesenchymal transition in embryonic development and in cancer, is shown to be involved in trophoblast differentiation as well. Moreover, Snail can be controlled by oxidative stress and hypoxia. Therefore, we examined the expression of Snail and its downstream target, e-cadherin, in human normal term, preterm and preeclamptic placentas, and in pregnant rats that developed preeclampsia-like symptoms in the response to a 20-fold increase in sodium intake.</p> <p>Methods</p> <p>Western blotting analysis was used for comparative expression of Snail and e- cadherin in total protein extracts. Placental cells expressing Snail and e-cadherin were identified by immunohistochemical double-labeling technique.</p> <p>Results</p> <p>The levels of Snail protein were decreased in human preeclamptic placentas by 30% (<it>p < 0.01) </it>compared to normal term, and in the rat model by 40% (<it>p < 0.001) </it>compared to control placentas. In preterm placentas, the levels of Snail expression varied, yet there was a strong trend toward statistical significance between preterm and preeclamptic placentas. In humans, e-cadherin protein level was 30% higher in preeclamptic <it>(p < 0.05) </it>placentas and similarly, but not significantly <it>(p = 0.1)</it>, high in the preterm placentas compared to normal term. In the rat model of preeclampsia, e-cadherin was increased by 60% (<it>p < 0.01)</it>. Immunohistochemical examination of human placentas demonstrated Snail-positive staining in the nuclei of the villous trophoblasts and mesenchymal cells and in the invasive trophoblasts of the decidua. In the rat placenta, the majority of Snail positive cells were spongiotrophoblasts of the junctional zone, while in the labyrinth, Snail-positive sinusoidal giant trophoblasts cells were found in some focal areas located close to the junctional zone.</p> <p>Conclusion</p> <p>We demonstrated that human preeclampsia and the salt-induced rat model of preeclampsia are associated with the reduced levels of Snail protein in placenta. Down-regulation of the transcription factor Snail in placental progenitor cell lineages, either by intrinsic defects and/or by extrinsic and maternal factors, may affect normal placenta development and function and thus contribute to the pathology of preeclampsia.</p

Numerical Study of Sediment Suspension Affected By Rigid Cylinders Under Unidirectional and Combined Wave-Current Flows

Sediment transport modeling for flows with cylinders is very challenging owing to the complicated flow–cylinder–sediment interactions, especially under the combined wave-current flows. In this paper, an improved formulation for incipient sediment suspension considering the effect of cylinder density (i.e., solid volume fraction) is employed to simulate the bottom sediment flux in the flow with cylinders. The proposed model is calibrated and validated using laboratory measurements under unidirectional and combined wave-current flows in previous studies. It is proved that the effects of cylinders on sediment suspension can be accounted for through a modified critical Shields number, and the proposed model is capable of simulating sediment suspension under both unidirectional and combined wave–current flows reasonably well with the average the coefficients of determination and model skills greater than 0.8 and 0.64

Peroxisome proliferator-activated receptor delta agonist, HPP593, prevents renal necrosis under chronic ischemia

The Goldblatt’s 2 kidney 1 clip (2K1C) rat animal model of renovascular hypertension is characterized by ischemic nephropathy of the clipped kidney. 2K1C rats were treated with a specific peroxisome proliferator-activated receptor δ (PPARδ) agonist, HPP593. Clipped kidneys from untreated rats developed tubular and glomerular necrosis and massive interstitial, periglomerular and perivascular fibrosis. HPP593 kidneys did not exhibit any histochemical features of necrosis; fibrotic lesions were present only in perivascular areas. Necrosis in the untreated clipped kidneys was associated with an increased oxidative stress, up regulation and mitochondrial translocation of the pro-death protein BNIP3 specifically in tubules. In the kidneys of HPP593-treated rats oxidative stress was attenuated and BNIP3 protein decreased notably in the mitochondrial fraction when compared to untreated animals. In untreated clipped kidneys, mitochondria were dysfunctional as revealed by perturbations in the levels of MCAD, COXIV, TFAM, and Parkin proteins and AMPK activation, while in HPP593-treated rats these proteins remained at the physiological levels. Nuclear amounts of oxidative stress-responsive proteins, NRF1 and NRF2 were below physiological levels in treated kidneys. Mitochondrial biogenesis and autophagy were inhibited similarly in both treated and untreated 2K1C kidneys as indicated by a decrease in PGC1-α and deficiency of the autophagy-essential proteins LC3-II and ATG5. However, HPP593 treatment resulted in increased accumulation of p62 protein, an autophagic substrate and an enhancer of NRF2 activity. Therefore, inhibition of BNIP3 activation by the preservation of mitochondrial function and control of oxidative stress by PPARδ is the most likely mechanism to account for the prevention of necrotic death in the kidney under conditions of persistent ischemia

Circulating Ouabain Modulates Expression of Claudins in Rat Intestine and Cerebral Blood Vessels

The ability of exogenous low ouabain concentrations to affect claudin expression and therefore epithelial barrier properties was demonstrated previously in cultured cell studies. We hypothesized that chronic elevation of circulating ouabain in vivo can affect the expression of claudins and tight junction permeability in different tissues. We tested this hypothesis in rats intraperitoneally injected with ouabain (1 μg/kg) for 4 days. Rat jejunum, colon and brain frontal lobes, which are variable in the expressed claudins and tight junction permeability, were examined. Moreover, the porcine jejunum cell line IPEC-J2 was studied. In IPEC-J2-cells, ouabain (10 nM, 19 days of incubation) stimulated epithelial barrier formation, increased transepithelial resistance and the level of cSrc-kinase activation by phosphorylation, accompanied with an increased expression of claudin-1, -5 and down-regulation of claudin-12; the expression of claudin-3, -4, -8 and tricellulin was not changed. In the jejunum, chronic ouabain increased the expression of claudin-1, -3 and -5 without an effect on claudin-2 and -4 expression. In the colon, only down-regulation of claudin-3 was observed. Chronic ouabain protected the intestine transepithelial resistance against functional injury induced by lipopolysaccharide treatment or by modeled acute microgravity; this regulation was most pronounced in the jejunum. Claudin-1 was also up-regulated in cerebral blood vessels. This was associated with reduction of claudin-3 expression while the expression of claudin-5 and occludin was not affected. Altogether, our results confirm that circulating ouabain can functionally and tissue-specifically affect barrier properties of epithelial and endothelial tissues via Na,K-ATPase-mediated modulation of claudins expression

Late consequences of classic congenital adrenal hyperplasia and its long-term poor control in men (case report and literature review)

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder of the adrenal cortex characterized by impairment of cortisol biosynthesis (with possible impairment of aldosterone biosynthesis) and excessive pituitary ACTH release, which promotes oversecretion of intact pathways products: 17-hydroxyprogesterone (17OHP), progesterone, and adrenal androgens &ndash; androstendione and testosterone. 21-hydroxylase deficiency, being the most common cause of congenital adrenal hyperplasia is a chronic disorder, that requires life-long glucocorticoid treatment, that aims both to replace cortisol and prevent ACTH-driven androgen excess. Nevertheless, reaching the optimal glucocorticoid dose is challenging because currently available glucocorticoid formulations cannot replicate the physiological circadian rhythm of cortisol secretion. The difficulties in striking the balance between uneffective normalizing of ACTH-level and excess glucocorticoid exposure leads to different abnormalities, that starts to develop at first months of life and progress, frequently gaining especial clinical meaning in adult age. In the present clinical case we introduce 35 years old male patient with salt-wasting form of 21-hydroxylase deficiency, which had either complications considered to progress due to insufficient glucocorticoid therapy, and some metabolic abnormalities, associated with supraphysiological doses of glucocorticoids

Transcriptomic changes triggered by ouabain in rat cerebellum granule cells: Role of α3- and α1-Na+,K+-ATPase-mediated signaling

It was shown previously that inhibition of the ubiquitous α1 isoform of Na+,K+-ATPase by ouabain sharply affects gene expression profile via elevation of intracellular [Na+]i/[K+]i ratio. Unlike other cells, neurons are abundant in the α3 isoform of Na+,K+-ATPase, whose affinity in rodents to ouabain is 104-fold higher compared to the α1 isoform. With these sharp differences in mind, we compared transcriptomic changes in rat cerebellum granule cells triggered by inhibition of α1- and α3-Na+,K+-ATPase isoforms. Inhibition of α1- and α3-Na+,K+-ATPase isoforms by 1 mM ouabain resulted in dissipation of transmembrane Na+ and K+ gradients and differential expression of 994 transcripts, whereas selective inhibition of α3-Na+,K+-ATPase isoform by 100 nM ouabain affected expression of 144 transcripts without any impact on the [Na+]i/[K+]i ratio. The list of genes whose expression was affected by 1 mM ouabain by more than 2-fold was abundant in intermediates of intracellular signaling and transcription regulators, including augmented content of Npas4, Fos, Junb, Atf3, and Klf4 mRNAs, whose upregulated expression was demonstrated in neurons subjected to electrical and glutamatergic stimulation. The role [Na+]i/[K+]i-mediated signaling in transcriptomic changes involved in memory formation and storage should be examined further