Method for Selection of New Primers for Identification of the Especially Dangerous Bacterium Acidovorax citrulli
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01.10.2018 |
Shneider Y.
Karimova E.
Smirnova I.
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Bulletin of Experimental Biology and Medicine |
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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. We propose a method for selection of new primers for identification of especially dangerous bacterium Acidovorax citrulli. A specific pair of new primers AC-1 F/R that can be used for detection and identification of A. citrulli was successfully tested. This opens up new possibilities for investigation of the role of this bacterium in the ecosystems.
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Bimaxillary orthognathic surgery with a conventional saw compared with the piezoelectric technique: a longitudinal clinical study
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01.10.2018 |
Rossi D.
Romano M.
Karanxha L.
Baserga C.
Russillo A.
Taschieri S.
Del Fabbro M.
Giannì A.
Baj A.
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British Journal of Oral and Maxillofacial Surgery |
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3 |
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© 2018 The British Association of Oral and Maxillofacial Surgeons The only cutting technique used for osteotomies in orthognathic surgery for many years has been a saw, but recently piezoelectric surgery has been introduced as a possible alternative. The aim of this study was to find out if piezoelectric surgery can be more comfortable for patients having orthognathic surgery. A total of 25 patients with dentofacial deformities (seven male and 18 female), were treated from January 2016 to September 2017. In 11 patients, osteotomies were made using a conventional saw, while in 14 a piezoelectric device was used. The variables assessed were: operating time, postoperative swelling, postoperative pain, and cutaneous sensitivity of the upper and lower lips. The duration of operation for the piezosurgery group was significantly longer than that for controls, but the patients had less swelling at all follow-up visits, and the difference was significant at the 30-day follow-up (p = 0.045). Those who had piezosurgery had significantly less pain at the three-day follow up (p = 0.035). There was a significant difference in cutaneous sensitivity only for the right side of the upper lip and only at the one-day follow-up. We conclude that piezoelectric surgery offers some advantages in lessening swelling and the perception of pain after orthognathic surgery, but further investigations are required.
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Genetic re-engineering of polyunsaturated phospholipid profile of Saccharomyces cerevisiae identifies a novel role for Cld1 in mitigating the effects of cardiolipin peroxidation
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01.10.2018 |
Lou W.
Ting H.
Reynolds C.
Tyurina Y.
Tyurin V.
Li Y.
Ji J.
Yu W.
Liang Z.
Stoyanovsky D.
Anthonymuthu T.
Frasso M.
Wipf P.
Greenberger J.
Bayır H.
Kagan V.
Greenberg M.
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Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids |
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© 2018 Elsevier B.V. Cardiolipin (CL) is a unique phospholipid localized almost exclusively within the mitochondrial membranes where it is synthesized. Newly synthesized CL undergoes acyl remodeling to produce CL species enriched with unsaturated acyl groups. Cld1 is the only identified CL-specific phospholipase in yeast and is required to initiate the CL remodeling pathway. In higher eukaryotes, peroxidation of CL, yielding CLOX, has been implicated in the cellular signaling events that initiate apoptosis. CLOX can undergo enzymatic hydrolysis, resulting in the release of lipid mediators with signaling properties. Our previous findings suggested that CLD1 expression is upregulated in response to oxidative stress, and that one of the physiological roles of CL remodeling is to remove peroxidized CL. To exploit the powerful yeast model to study functions of CLD1 in CL peroxidation, we expressed the H. brasiliensis Δ12-desaturase gene in yeast, which then synthesized poly unsaturated fatty acids(PUFAs) that are incorporated into CL species. Using LC-MS based redox phospholipidomics, we identified and quantified the molecular species of CL and other phospholipids in cld1Δ vs. WT cells. Loss of CLD1 led to a dramatic decrease in chronological lifespan, mitochondrial membrane potential, and respiratory capacity; it also resulted in increased levels of mono-hydroperoxy-CLs, particularly among the highly unsaturated CL species, including tetralinoleoyl-CL. In addition, purified Cld1 exhibited a higher affinity for CLOX, and treatment of cells with H2O2 increased CLD1 expression in the logarithmic growth phase. These data suggest that CLD1 expression is required to mitigate oxidative stress. The findings from this study contribute to our overall understanding of CL remodeling and its role in mitigating oxidative stress.
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Novel aminochromone derivative inhibits tumor growth on xenograft model of lung cancer in mice
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01.10.2018 |
Blinova E.
Dudina M.
Suslova I.
Samishina E.
Blinov D.
Roshchin D.
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Journal of Advanced Pharmaceutical Technology and Research |
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© 2018 Medknow Publications. All rights reserved. 2-Amino-4H-chromene derivatives possess anticancer property proved on different in vivo and in vitro models of malignancies such breast, nasopharyngeal, bladder, ovary carcinomas, astrocytoma, and osteosarcoma. We assumed it might be effective to apply one of the derivatives as promising approach to lung carcinoma treatment.To evaluate how novel 4-Aryl substituted 2-Amino-4H-chromene derivative AX-554 impacts tumor growth and progression, as well as possible mechanisms for anticancer effect development on in vivo patient-derived heterotopic xenograft model of lung carcinoma in mice. This was an experimental in vivo study. 40 nu/nu BALB/c female mice were randomly allocated into four equal groups: Intact, control, reference, and main group. Animals of three latter groups were ingrafted with human-derived lung adenocarcinoma. Antitumor and antimetastatic action of AX-554 novel aminochromone derivative as a substance were studied. Mice survival was registered. Kinase of anaplastic lymphoma (ALK), tubulin Beta-3 (TUBB3), and c-mesenchymal-epithelial transition (MET) concentrations in the prime tumor nodes homogenates were determined by quantitative enzyme-linked immunosorbent assay. Dannet's parametric criterion and the nonparametric exact Fisher test were used. The normality of the distribution was determined using ANOVA. The survival curve was analyzed using Gehan's criterion with the Yates's correction. Aminochromone derivative possesses an inhibitory effect on human lung adenocarcinoma transplanted into nu/nu BALB/c female mice, as well as significant antimetastatic activity. About 50 mg/kg/day AX-554 intragastric course increases animals' life expectancy of more than 3.3 times when compared with the control and induces remission in 60% of cases. The anticancer effect of the derivative is due to anti-ALK-mediated activation of tumor cells apoptosis and suppression TUBB3-dependent cell proliferation.
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Wound healing by the use of scalpel and various radio-frequency cutting devices (A randomized experimental study)
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01.10.2018 |
Stupin V.
Manturova N.
Kogan E.
Smirnova G.
Polivoda M.
Silina E.
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International Journal of Pharmaceutical Research |
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© 2018, Advanced Scientific Research. All rights reserved. An experimental study was performed on Wistar rats with the purpose of histological evaluation of the surgical wounds state and the processes of their healing using a conventional surgical scalpel and three radio wave devices with different operating frequencies (2.2 MHz, 2.64 MHz, 3.8 MHz). It has been established that in animals with wounds inflicted by the radio-wave at the highestworking frequency, there were statistically significant differences both in terms and in the mechanisms of wound healing. These benefits were in the absence of a blood clot in the wound after the incision, also in minimal necrosis of the operating wound and adjacent tissues, in the absence of leukocyte infiltration in the wound; early (from 3 days) reparation and epithelialization of tissues. These features contributed to a reduction in the timing of wound healing and the absence of scar formation.
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The Expression of Matryoshka Gene Encoding a Homologue of Kunitz Peptidase Inhibitor Is Regulated Both at the Level of Transcription and Translation
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01.10.2018 |
Sheshukova E.
Komarova T.
Ershova N.
Bronstein A.
Dorokhov Y.
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Biochemistry (Moscow) |
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© 2018, Pleiades Publishing, Ltd. The gene for Kunitz peptidase inhibitor-like protein (KPILP) contains nested alternative open reading frame (aORF) that controls expression of the maternal mRNA. The content of NbKPILP mRNA in intact leaves of Nicotiana benthamiana plant is low but increases significantly upon extended dark exposure or when foreign nucleic acid is overexpressed in the cells. The NbKPILP gene promoter along with the expressed nested aORF are likely to play an important role in maintaining the levels of NbKPILP mRNA. To elucidate the role of NbKPILP promoter, we isolated a fragment of N. benthamiana chromosomal DNA upstream of the NbKPILP transcription start, sequenced it, and created constructs in which reporter E. coli uidA gene coding for β-D-glucuronidase (GUS) was placed under control of the NbKPILP promoter. By assessing the efficacy of uidA mRNA synthesis directed by the NbKPILP promoter and 35S promoter of the cauliflower mosaic virus in a transient expression system, we showed that the levels of GUS accumulation were comparable for both promoters. Prolonged incubation of the agroinjected plants in the darkness stimulated accumulation of the uidA mRNA directed by the NbKPILP promoter. Our experiments indicate that along with regulation at the transcriptional level, expression of NbKPILP mRNA can be affected by expression of the nested aORF controlled by the polypurine block (PPB) located upstream of its start codon, since introduction of mutations in the PPB resulted in significant accumulation of the NbKPILP mRNA. Nucleotide replacement in the aORF start codon led to the drastic increase in the amounts of NbKPILP mRNA and its protein product.
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Sleep-Wake Disorders in Stroke—Increased Stroke Risk and Deteriorated Recovery? An Evaluation on the Necessity for Prevention and Treatment
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01.10.2018 |
Duss S.
Brill A.
Bargiotas P.
Facchin L.
Alexiev F.
Manconi M.
Bassetti C.
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Current Neurology and Neuroscience Reports |
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4 |
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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Purpose of Review: Sleep-wake disorders (SWD) are common not only in the general population but also in stroke patients, in whom SWD may be pre-existent or appear “de novo” as a consequence of brain damage. Despite increasing evidence of a negative impact of SWD on cardiocerebrovascular risk, cognitive functions, and quality of life, SWD are insufficiently considered in the prevention and management of patients with stroke. This narrative review aims at summarizing the current data on the bidirectional link between SWD and stroke. Recent Findings: Several studies have demonstrated that sleep-disordered breathing (SDB) is an independent risk factor for stroke and has a detrimental effect on stroke recovery. Short and long sleep duration and possibly other SWD (e.g., insomnia, circadian rhythm disorders) may also increase the risk of stroke and influence its outcome. Data on SDB treatment increasingly indicate a benefit on stroke risk and evolution while treatment of other SWD is still limited. Summary: A systematic search for SWD in stroke patients is justified due to their high frequency and their negative impact on stroke outcomes. Clinicians should actively consider available treatment options.
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API-Sociology and Google Global society: Confluence of factors for political and economic awareness
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01.10.2018 |
Mazelis L.
Mazelis A.
Shamshurina N.
Kolesnichenko Y.
Yakovleva D.
Kolesnichenko O.
Zykova A.
Grigorevsky I.
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IEEE 12th International Conference on Application of Information and Communication Technologies, AICT 2018 - Proceedings |
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© 2018 IEEE. Text Big Data Analytics Study is presented (frequency-morphological analysis of open texts from Google). Visualization of Morphological Matrix, cluster analysis (hierarchical method of dendrograms creation), and Value Chain Map were implemented as the set of tools for analytics. World Economic Forum's Global Risks Report was taken as a model in studying global issues. Global Trends Map was created and is presented; it indicates global social persistent inequality. Our results were compared with Global Risks Report and Multiple Futures Project-2030. Value Chain Map, based on Text Big Data Analytics for eight countries, helped to assess economic situation in terms of competitiveness at the global market.
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Effects of Novel Potential Analgesic Compounds on the Cardiovascular and Respiratory Systems
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01.10.2018 |
Palikova Y.
Skobtsova L.
Palikov V.
Belous G.
Khokhlova O.
Lobanov A.
Slashcheva G.
Rzhevskii D.
Rudenko V.
Kalabina E.
Osipova G.
Andreev Y.
Logashina Y.
Kozlov S.
Yavorskii A.
Elyakova G.
D’yachenko I.
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Pharmaceutical Chemistry Journal |
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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The polypeptide analgesic compounds APCH3 (a TRPV1 receptor inhibitor) and PT1 (a P 2 X 3 receptor inhibitor) were shown not to act on the cardiovascular system or respiratory system when given either as single or multiple doses in mice. The low molecular weight compound sevanol (an ASIC3 receptor inhibitor) had no effect on the cardiovascular system, but prolonged use for 14 days affected measures of the respiratory system, significantly increasing respiratory rate and peak expiratory flow rate.
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Regenerative Potential of Spinal Ganglion Neurons During Topical Administration of Platelet-Enriched Blood Plasma Into the Skin Wound
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01.10.2018 |
Fetisov S.
Nikityuk D.
Klochkova S.
Alekseeva N.
Kvaratskheliya A.
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Bulletin of Experimental Biology and Medicine |
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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. We studied the reactions of spinal ganglion neurons accompanying regeneration of the skin wound complicated by S. aureus sp. infection. The appearance of neuron groups with different morphofunctional changes was noted: reversible dystrophic and compensatory reactions and irreversible degenerative changes. The proportion of small B neurons was higher than the proportion of large type A neurons at all terms of the experiment. Application of plateletrich plasma to the wound after preliminary hydroimpulsive treatment considerably reduced cell destruction and stimulated regenerative effects in neurons starting from day 7 of the experiment. Application of platelet-rich plasma without hydroimpulsive treatment decelerated wound regeneration and increased the number of destructively changed neurons even in comparison with spontaneous wound healing. Close correlations between protein synthesis markers and stages of the wound process and its characteristics were revealed.
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Genetic ablation of adenosine receptor A3 results in articular cartilage degeneration
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01.10.2018 |
Shkhyan R.
Lee S.
Gullo F.
Li L.
Peleli M.
Carlstrom M.
Chagin A.
Banks N.
Limfat S.
Liu N.
Evseenko D.
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Journal of Molecular Medicine |
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© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Abstract: Osteoarthritis (OA), the most common form of arthritis, is characterized by inflammation of joints and cartilage degradation leading to disability, discomfort, severe pain, inflammation, and stiffness of the joint. It has been shown that adenosine, a purine nucleoside composed of adenine attached to ribofuranose, is enzymatically produced by the human synovium. However, the functional significance of adenosine signaling in homeostasis and pathology of synovial joints remains unclear. Adenosine acts through four cell surface receptors, i.e., A1, A2A, A2B, and A3, and here, we have systematically analyzed mice with a deficiency for A3 receptor as well as pharmacological modulations of this receptor with specific analogs. The data show that adenosine receptor signaling plays an essential role in downregulating catabolic mechanisms resulting in prevention of cartilage degeneration. Ablation of A3 resulted in development of OA in aged mice. Mechanistically, A3 signaling inhibited cellular catabolic processes in chondrocytes including downregulation of Ca2+/calmodulin-dependent protein kinase (CaMKII), an enzyme that promotes matrix degradation and inflammation, as well as Runt-related transcription factor 2 (RUNX2). Additionally, selective A3 agonists protected chondrocytes from cell apoptosis caused by pro-inflammatory cytokines or hypo-osmotic stress. These novel data illuminate the protective role of A3, which is mediated via inhibition of intracellular CaMKII kinase and RUNX2 transcription factor, the two major pro-catabolic regulators in articular cartilage. Key messages: Adenosine receptor A3 (A3) knockout results in progressive loss of articular cartilage in vivo.Ablation of A3 results in activation of matrix degradation and cartilage hypertrophy.A3 agonists downregulate RUNX2 and CaMKII expression in osteoarthritic human articular chondrocytes.A3 prevents articular cartilage matrix degradation induced by inflammation and osmotic fluctuations.A3 agonist inhibits proteolytic activity of cartilage-degrading enzymes.
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Influence of aging-induced flow waveform variation on hemodynamics in aneurysms present at the internal carotid artery: A computational model-based study
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01.10.2018 |
Xu L.
Liang F.
Zhao B.
Wan J.
Liu H.
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Computers in Biology and Medicine |
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4 |
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© 2018 Elsevier Ltd The variation of blood flow waveform in the internal carotid artery (ICA) with age is a well-documented hemodynamic phenomenon, but little is known about how such variation affects the characteristics of blood flow in aneurysms present in the region. In the study, hemodynamic simulations were conducted for 26 ICA aneurysms, with flow waveforms measured in the ICAs of young and older adults being used respectively to set the inflow boundary conditions. Obtained results showed that replacing the young-adult flow waveform with the older-adult one led to little changes (<10%) in simulated time-averaged wall shear stress (WSS), transient maximum WSS, relative residence time and trans-aneurysm pressure loss coefficient, but resulted in a marked increase (32.36 ± 17.24%) in oscillatory shear index (OSI). Frequency-domain wave analysis revealed that the progressive enhancement of low-frequency harmonics dominated the observed flow waveform variation with age and was a major factor contributing to the increase in OSI. Cross-sectional comparisons among the aneurysms further revealed that the degree of increase in OSI correlated positively with some specific morphological features of aneurysm, such as aspect ratio and size ratio. In summary, the study demonstrates that the variation in flow waveform with age augments the oscillation of WSS in ICA aneurysms, which underlies the importance of setting patient-specific boundary conditions in hemodynamic studies on cerebral aneurysms, especially those involving long-term patient follow-up or cross-sectional comparison among patients of different ages.
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Obtaining of highly-active catalysts of unsaturated compounds hydrogenation by using supercritical carbon dioxide
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01.10.2018 |
Parenago O.
Timashev P.
Karakhanov E.
Maximov A.
Lazhko A.
Zolotukhina A.
Bagratashvili V.
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Journal of Supercritical Fluids |
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© 2018 Elsevier B.V. Polymer frameworks have been for the first time impregnated with rhodium and palladium compounds in a supercritical carbon dioxide medium. The polymeric carriers were the mesoporous phenol-formaldehyde resin and cross-linked dendrimer networks, based on poly(propylene imine) and poly(amido amine) dendrimers. The metal compounds were rhodium acetylacetonate and palladium carboxylates including their fluoro-substituted derivatives and palladium hexafluoroacetylacetonate. Using the IR-spectroscopy method, we have shown that the metal content in the polymers was in the range of 0.3–2.0 wt.% depending on the polymer nature, cross-linking agent type and cross-linking degree. We have obtained the samples of polymer supports with nanosized metal particles through hydrogen reduction of immobilized rhodium and palladium compounds at P(H 2 ) = 6–10 MPa, T = 60 °C, 4 h time. The average rhodium particle size was 1–2 nm. It has been shown that the obtained nanocomposites were extremely active catalysts for hydrogenation of unsaturated hydrocarbons.
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Advances in the Application of Modified Nucleotides in SELEX Technology
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01.10.2018 |
Antipova O.
Zavyalova E.
Golovin A.
Pavlova G.
Kopylov A.
Reshetnikov R.
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Biochemistry (Moscow) |
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© 2018, Pleiades Publishing, Ltd. Aptamers are widely used as molecular recognition elements for detecting and blocking functional biological molecules. Since the common “alphabet” of DNA and RNA consists of only four letters, the chemical diversity of aptamers is less than the diversity of protein recognition elements built of 20 amino acids. Chemical modification of nucleotides enlarges the potential of DNA/RNA aptamers. This review describes the latest achievements in a variety of approaches to aptamers selection with an extended genetic alphabet.
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Tooth Survival after Surgical or Nonsurgical Endodontic Retreatment: Long-term Follow-up of a Randomized Clinical Trial
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01.10.2018 |
Riis A.
Taschieri S.
Del Fabbro M.
Kvist T.
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Journal of Endodontics |
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© 2018 American Association of Endodontists Introduction: The aim of the study was to determine long-term tooth survival after endodontic retreatment and whether the presence of intraradicular posts influences the outcome. Methods: Ninety-five teeth were randomly assigned to surgical or nonsurgical endodontic retreatment. Forty-seven teeth in 45 patients were treated by conventional endodontic surgery and 48 teeth (47 patients) by nonsurgical retreatment, including the removal of intraradicular posts in 37 (77%). The outcome was tooth survival; follow-up continued until the tooth had been extracted, at least 10 years had elapsed since retreatment, the patient declined further follow-up, or the patient died. The Fisher exact test was used to analyze differences between the groups. Results: The median follow-up time was 10.1 years (range, 0.0–15.6 years). The overall survival rate was 76%, with no significant differences in long-term tooth survival between retreatment methods or the presence of an intraradicular post. The reasons for tooth extraction were related to the retreatment method. Vertical root fractures were significantly more frequent in the nonsurgical group when retreatment included post removal (P =.036). Conclusions: There was no significant difference in long-term tooth survival after surgical or nonsurgical retreatment. The presence of intraradicular posts did not affect long-term tooth survival, but for teeth with posts, those retreated nonsurgically were more frequently extracted because of vertical root fractures than those retreated surgically (P =.036). The major limitations of the study were a smaller sample size and the use of outmoded retreatment techniques.
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Neurological, sensorimotor and cardiorespiratory alterations induced by methoxetamine, ketamine and phencyclidine in mice
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01.10.2018 |
Ossato A.
Bilel S.
Gregori A.
Talarico A.
Trapella C.
Gaudio R.
De-Giorgio F.
Tagliaro F.
Neri M.
Fattore L.
Marti M.
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Neuropharmacology |
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© 2018 Elsevier Ltd Novel psychoactive substances are intoxicating compounds developed to mimic the effects of well-established drugs of abuse. They are not controlled by the United Nations drug convention and pose serious health concerns worldwide. Among them, the dissociative drug methoxetamine (MXE) is structurally similar to ketamine (KET) and phencyclidine (PCP) and was created to purposely mimic the psychotropic effects of its “parent” compounds. Recent animal studies show that MXE is able to stimulate the mesolimbic dopaminergic transmission and to induce KET-like discriminative and rewarding effects. In light of the renewed interest in KET and PCP analogs, we decided to deepen the investigation of MXE-induced effects by a battery of behavioral tests widely used in studies of “safety-pharmacology” for the preclinical characterization of new molecules. To this purpose, the acute effects of MXE on neurological and sensorimotor functions in mice, including visual, acoustic and tactile responses, thermal and mechanical pain, motor activity and acoustic startle reactivity were evaluated in comparisons with KET and PCP to better appreciate its specificity of action. Cardiorespiratory parameters and blood pressure were also monitored in awake and freely moving animals. Acute systemic administrations of MXE, KET and PCP (0.01–30 mg/kg i.p.) differentially alter neurological and sensorimotor functions in mice depending in a dose-dependent manner specific for each parameter examined. MXE and KET (1 and 30 mg/kg i.p.) and PCP (1 and 10 mg/kg i.p.) also affect significantly cardiorespiratory parameters, systolic and diastolic blood pressure in mice.
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A multi-scale model of the coronary circulation applied to investigate transmural myocardial flow
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01.10.2018 |
Ge X.
Yin Z.
Fan Y.
Vassilevski Y.
Liang F.
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International Journal for Numerical Methods in Biomedical Engineering |
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5 |
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© 2018 John Wiley & Sons, Ltd. Distribution of blood flow in myocardium is a key determinant of the localization and severity of myocardial ischemia under impaired coronary perfusion conditions. Previous studies have extensively demonstrated the transmural difference of ischemic vulnerability. However, it remains incompletely understood how transmural myocardial flow is regulated under in vivo conditions. In the present study, a computational model of the coronary circulation was developed to quantitatively evaluate the sensitivity of transmural flow distribution to various cardiovascular and hemodynamic factors. The model was further incorporated with the flow autoregulatory mechanism to simulate the regulation of myocardial flow in the presence of coronary artery stenosis. Numerical tests demonstrated that heart rate (HR), intramyocardial tissue pressure (Pim), and coronary perfusion pressure (Pper) were the major determinant factors for transmural flow distribution (evaluated by the subendocardial-to-subepicardial (endo/epi) flow ratio) and that the flow autoregulatory mechanism played an important compensatory role in preserving subendocardial perfusion against reduced Pper. Further analysis for HR variation-induced hemodynamic changes revealed that the rise in endo/epi flow ratio accompanying HR decrease was attributable not only to the prolongation of cardiac diastole relative to systole, but more predominantly to the fall in Pim. Moreover, it was found that Pim and Pper interfered with each other with respect to their influence on transmural flow distribution. These results demonstrate the interactive effects of various cardiovascular and hemodynamic factors on transmural myocardial flow, highlighting the importance of taking into account patient-specific conditions in the explanation of clinical observations.
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Aberrant cardiolipin metabolism is associated with cognitive deficiency and hippocampal alteration in tafazzin knockdown mice
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01.10.2018 |
Cole L.
Kim J.
Amoscato A.
Tyurina Y.
Bayır H.
Karimi B.
Siddiqui T.
Kagan V.
Hatch G.
Kauppinen T.
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Biochimica et Biophysica Acta - Molecular Basis of Disease |
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3 |
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© 2018 Elsevier B.V. Cardiolipin (CL) is a key mitochondrial phospholipid essential for mitochondrial energy production. CL is remodeled from monolysocardiolipin (MLCL) by the enzyme tafazzin (TAZ). Loss-of-function mutations in the gene which encodes TAZ results in a rare X-linked disorder called Barth Syndrome (BTHS). The mutated TAZ is unable to maintain the physiological CL:MLCL ratio, thus reducing CL levels and affecting mitochondrial function. BTHS is best known as a cardiac disease, but has been acknowledged as a multi-syndrome disorder, including cognitive deficits. Since reduced CL levels has also been reported in numerous neurodegenerative disorders, we examined how TAZ-deficiency impacts cognitive abilities, brain mitochondrial respiration and the function of hippocampal neurons and glia in TAZ knockdown (TAZ kd) mice. We have identified for the first time the profile of changes that occur in brain phospholipid content and composition of TAZ kd mice. The brain of TAZ kd mice exhibited reduced TAZ protein expression, reduced total CL levels and a 19-fold accumulation of MLCL compared to wild-type littermate controls. TAZ kd brain exhibited a markedly distinct profile of CL and MLCL molecular species. In mitochondria, the activity of complex I was significantly elevated in the monomeric and supercomplex forms with TAZ-deficiency. This corresponded with elevated mitochondrial state I respiration and attenuated spare capacity. Furthermore, the production of reactive oxygen species was significantly elevated in TAZ kd brain mitochondria. While motor function remained normal in TAZ kd mice, they showed significant memory deficiency based on novel object recognition test. These results correlated with reduced synaptophysin protein levels and derangement of the neuronal CA1 layer in hippocampus. Finally, TAZ kd mice had elevated activation of brain immune cells, microglia compared to littermate controls. Collectively, our findings demonstrate that TAZ-mediated remodeling of CL contributes significantly to the expansive distribution of CL molecular species in the brain, plays a key role in mitochondria respiratory activity, maintains normal cognitive function, and identifies the hippocampus as a potential therapeutic target for BTHS.
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Comparison of short-term and medium-term swimming training on cardiodynamics and coronary flow in high salt-induced hypertensive and normotensive rats
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01.10.2018 |
Plecevic S.
Jakovljevic B.
Savic M.
Zivkovic V.
Nikolic T.
Jeremic J.
Milosavljevic I.
Srejovic I.
Tasic N.
Djuric D.
Jakovljevic V.
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Molecular and Cellular Biochemistry |
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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The aim of present study was to evaluate the effects of 3- and 6-week swimming exercise on cardiodynamics and coronary flow in high salt-induced hypertensive and normotensive rats. 80 male Wistar albino rats (6 weeks old) were divided into 8 groups: hypertensive animals that swam for 3 weeks; hypertensive animals that swam for 6 weeks and their respective sedentary controls; normotensive animals that swam for 3 weeks; normotensive animals that swam for 6 weeks and their respective sedentary controls. Hypertensive animals were on high sodium (8% NaCl solution) diet for 4 weeks, and these animals did not drink tap water during the experimental protocol. After sacrificing, hearts were isolated and perfused according to Langendorff technique at gradually increased coronary perfusion pressure (40–120 cmH2O). The following parameters of cardiac function were continuously recorded: maximum and minimum rate of pressure development in LV, systolic, and diastolic left ventricular pressure, and heart rate. Coronary flow was measured flowmetrically. Findings of the present study may help in better understanding of short- to medium-term exercise-induced direct effects on cardiac function and perfusion. Generally viewed, swimming of both durations did not change myocardial function and perfusion in hypertensive and normotensive conditions.
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Study of Genetic Diversity and Population Structure of the Yak (Bos grunniens) in the Sayan-Altai Region
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01.10.2018 |
Oyun N.
Konorov E.
Urum A.
Artyushin I.
Svishcheva G.
Cendsuren C.
Stolpovsky Y.
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Russian Journal of Genetics |
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© 2018, Pleiades Publishing, Inc. Abstract: The paper reports the first study of genetic diversity of the domestic yak in the Sayan-Altai region of Russia (Altai and Tuva) and Mongolia (Khuvsgul and Gobi) on the basis of the polymorphism analysis of the mtDNA D-loop hypervariable region. It has been demonstrated that, among all the studied populations, Tuva yaks are characterized by the highest haplotype diversity. Four new haplotypes, A4, A13, D9, and E3, have been described for the first time. The analysis of the contribution of maternal genetic component to the yak intrabreed and interbreed mtDNA diversity revealed two large clades. For the first time, comparative analysis of genetic structure of the Russian yak populations was carried out using 15 microsatellite loci. Low genetic difference between the populations was revealed, which may apparently be accounted for by the specific features of farm breeding, in particular, by animal exchange between the adjacent territories of the Sayan-Altai region.
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