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31.
Srdjan M. Vlajkovic Kyu-Hyun Lee Ann Chi Yan Wong Cindy X. Guo Rita Gupta Gary D. Housley Peter R. Thorne 《Purinergic signalling》2010,6(2):273-281
Hearing loss from noise exposure is a leading occupational disease, with up to 5% of the population at risk world-wide. Here,
we present a novel purine-based pharmacological intervention that can ameliorate noise-induced cochlear injury. Wistar rats
were exposed to narrow-band noise (8–12 kHz, 110 dB SPL, 2–24 h) to induce cochlear damage and permanent hearing loss. The
selective adenosine A1 receptor agonist, adenosine amine congener (ADAC), was administered intraperitoneally (100 μg/kg/day) at time intervals after
noise exposure. Hearing thresholds were assessed using auditory brainstem responses and the hair cell loss was evaluated by
quantitative histology. Free radical damage in the organ of Corti was assessed using nitrotyrosine immunohistochemistry. The
treatment with ADAC after noise exposure led to a significantly greater recovery of hearing thresholds compared with controls.
These results were upheld by increased survival of sensory hair cells and reduced nitrotyrosine immunoreactivity in ADAC-treated
cochlea. We propose that ADAC could be a valuable treatment for noise-induced cochlear injury in instances of both acute and
extended noise exposures. 相似文献
32.
Mary G. O’Keeffe Peter R. Thorne Gary D. Housley Simon C. Robson Srdjan M. Vlajkovic 《Purinergic signalling》2010,6(2):249-261
Membrane-bound ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) in the inner ear regulate complex extracellular
purinergic type-2 (P2) receptor signalling pathways through hydrolysis of extracellular nucleoside 5′-triphosphates and diphosphates.
This study investigated the distribution of NTPDase5 and NTPDase6, two intracellular members of the E-NTPDase family, and
linked this to regulation of P2 receptor signalling in the adult rat cochlea. These extracellular ectonucleotidases preferentially
hydrolyse nucleoside 5′-diphosphates such as UDP and GDP. Expression of both enzymes at mRNA and protein level was detected
in cochlear tissues and there was in vivo release of soluble NTPDase5 and 6 into cochlear fluids. Strong NTPDase5 immunostaining
was found in the spiral ganglion neurones and supporting Deiters’ cells of the organ of Corti, while NTPDase6 was confined
to the inner hair cells. Upregulation of NTPDase5 after exposure to loud sound indicates a dynamic role for NTPDase5 in cochlear
response to stress, whereas NTPDase6 may have more limited extracellular roles. Noise-induced upregulation of co-localised
UDP-preferring P2Y6 receptors in the spiral ganglion neurons further supports the involvement of NTPDase5 in regulation of P2Y receptor signalling.
Noise stress also induced P2Y14 (UDP- and UDP-glucose preferring) receptor expression in the root processes of the outer sulcus cells, but this was not associated
with localization of the E-NTPDases. 相似文献
33.
Little is known about the expression pattern of vascular endothelial growth factor (VEGF) among smooth muscle cells of different
arterial regions. Therefore, we have conducted studies aimed at increasing expression of VEGF in cultured human smooth muscle
cells (SMCs) from different sites: aorta, umbilical artery, and coronary artery. Two plasmids harboring human VEGF121 and VEGF165 isoforms, respectively, were constructed and lipotransfected into vascular SMCs, using the Fu-GENE 6. Extensive optimization
of transfection conditions were performed prior to this.
Different basal levels of VEGF were observed between cell types: from 0.51–0.95 pg/mL/μg protein in umbilical artery, through
2.32–2.39 pg/mL/μg protein in coronary artery, to 5.45–7.52 pg/mL/μg protein in aortic SMCs. Significant differences in responses
to transfection were also observed: The increase in VEGF production was most pronounced in umbilical artery SMCs (e.g., with
4 μg VEGF121-cDNA/in the wells)—an approximate 600-fold as opposed to an 18-fold increase in aortic SMCs and a 29-fold increase in coronary
artery SMCs.
In addition, we observed significant increases in proliferation rate of aortic and coronary endothelial cells (ECs), after
incubation with conditioned medium from VEGF-transfected SMCs. Observed changes differed in relation to cell origin and isoform. 相似文献
34.
Stepanović S Dakić I Martel A Vaneechoutte M Morrison D Shittu A Jezek P Decostere A Devriese LA Haesebrouck F 《Systematic and applied microbiology》2005,28(4):353-357
Members of the Staphylococcus sciuri group (S. sciuri, S. lentus, and S. vitulinus) are coagulase-negative, novobiocin-resistant staphylococci that could be distinguished from other staphylococci on the basis of positive oxidase activity. In the present study, a scheme based on conventional methods and utilization of various carbohydrates was evaluated for the identification of oxidase-positive staphylococci, and validated using two molecular techniques. Of the 173 oxidase-positive staphylococcal tested strains, 161 were identified as S. sciuri, 9 as S. lentus, 2 as S. vitulinus, and one as S. fleurettii by our scheme. The level of agreement with tRNA intergenic length polymorphism analysis (tDNA-PCR) was high (97.5-100% correlation). The accuracy and ease of use of this protocol suggest that it may be useful and valuable in microbiological laboratories for the identification of members of this group. 相似文献
35.
Martin M. Johansson Anneleen Van Geystelen Maarten H. D. Larmuseau Srdjan Djurovic Ole A. Andreassen Ingrid Agartz Elena Jazin 《PloS one》2015,10(8)
Background
The human Y chromosome is almost always excluded from genome-wide investigations of copy number variants (CNVs) due to its highly repetitive structure. This chromosome should not be forgotten, not only for its well-known relevance in male fertility, but also for its involvement in clinical phenotypes such as cancers, heart failure and sex specific effects on brain and behaviour.Results
We analysed Y chromosome data from Affymetrix 6.0 SNP arrays and found that the signal intensities for most of 8179 SNP/CN probes in the male specific region (MSY) discriminated between a male, background signals in a female and an isodicentric male containing a large deletion of the q-arm and a duplication of the p-arm of the Y chromosome. Therefore, this SNP/CN platform is suitable for identification of gain and loss of Y chromosome sequences. In a set of 1718 males, we found 25 different CNV patterns, many of which are novel. We confirmed some of these variants by PCR or qPCR. The total frequency of individuals with CNVs was 14.7%, including 9.5% with duplications, 4.5% with deletions and 0.7% exhibiting both. Hence, a novel observation is that the frequency of duplications was more than twice the frequency of deletions. Another striking result was that 10 of the 25 detected variants were significantly overrepresented in one or more haplogroups, demonstrating the importance to control for haplogroups in genome-wide investigations to avoid stratification. NO-M214(xM175) individuals presented the highest percentage (95%) of CNVs. If they were not counted, 12.4% of the rest included CNVs, and the difference between duplications (8.9%) and deletions (2.8%) was even larger.Conclusions
Our results demonstrate that currently available genome-wide SNP platforms can be used to identify duplications and deletions in the human Y chromosome. Future association studies of the full spectrum of Y chromosome variants will demonstrate the potential involvement of gain or loss of Y chromosome sequence in different human phenotypes. 相似文献36.
Ljubisavljevic S Stojanovic I Pavlovic D Sokolovic D Stevanovic I 《Redox report : communications in free radical research》2011,16(4):166-172
Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of human multiple sclerosis (MS). We have evaluated the role of oxidative and nitrosative stress, as the causal factors in the development of EAE, responsible for the damage of cardinal cellular components, such as lipids, proteins and nucleic acids, resulting in demyelination, axonal damage, and neuronal death. EAE was induced in female Sprague-Dawley rats, 3 months old (300±20 g), by immunization with myelin basic protein in combination with Complete Freund's adjuvant (CFA). The animals were divided into seven groups: control, EAE, CFA, EAE+aminoguanidine (AG), AG, EAE+N-acetyl-L-cysteine (NAC) and NAC. The animals were sacrificed 15 days after EAE induction, and the levels of nitrosative and oxidative stress were determined in 10% homogenate of the whole encephalitic mass. In EAE rats, brain NO production and MDA level were significantly increased (P<0.001) compared to the control values, whereas AG and NAC treatment decreased both parameters in EAE rats compared to EAE group (P<0.001). Glutathione (GSH) was reduced (P<0.001) in EAE rats in comparison with the control and CFA groups, but increased in EAE+AG and EAE+NAC group compared to the EAE group (P<0.01). Superoxide dismutase (SOD) activity was significantly decreased (P<0.001) in the EAE group compared to all other experimental groups. The clinical expression of EAE was significantly decreased (P<0.05) in the EAE groups treated with AG and NAC compared to EAE rats, during disease development. The obtained results prove an important role of oxidative and nitrosative stress in the pathogenesis of EAE, whereas AG and NAC protective effects offer new possibilities for a modified combined approach in MS therapy. 相似文献
37.
Bojović S Nikolić B Ristić M Orlović S Veselinović M Rakonjac L Dražić D 《化学与生物多样性》2011,8(9):1754-1765
The particular significance of the whitebark pine (Pinus heldreichii Christ.) stems from the fact that it is a tertiary relict and Balkanic subendemite covering a very narrow and intermittent area in Serbia. A representative pool of 48 adult trees originating from three populations, one recently discovered natural (Population I) and two planted populations (Populations II and III) was investigated in order to evaluate the intra- and interpopulation variability of the essential oil of the complete fund of P. heldreichii in Serbia. In the pine-needle-terpene profile, 104 compounds were detected, 84 of which could be identified. Among the essential-oil constituents, monoterpenes and sesquiterpenes dominated, comprising ca. 90% of the essential oil. The terpenic profile of Population I was characterized by a predominance of monoterpenes (e.g., limonene (1), α-pinene, and Δ(3) -carene (4)), while sesquiterpenes (e.g., germacrene D (2) and β-caryophyllene (3)) obviously preponderated in the profile of Populations II and III. This study also demonstrated that the abundance of whitebark pines in Serbia had significantly changed over the last few decades. The number of individuals in the natural population had increased, while the number of individuals in the planted populations had decreased. Today, the whitebark pine fund in Serbia comprises less than 250 trees. 相似文献
38.
Martin Tesli Kristina C. Skatun Olga Therese Ousdal Andrew Anand Brown Christian Thoresen Ingrid Agartz Ingrid Melle Srdjan Djurovic Jimmy Jensen Ole A. Andreassen 《PloS one》2013,8(2)
Objectives
Several genetic studies have implicated the CACNA1C SNP rs1006737 in bipolar disorder (BD) and schizophrenia (SZ) pathology. This polymorphism was recently found associated with increased amygdala activity in healthy controls and patients with BD. We performed a functional Magnetic Resonance Imaging (fMRI) study in a sample of BD and SZ cases and healthy controls to test for altered amygdala activity in carriers of the rs1006737 risk allele (AA/AG), and to investigate if there were differences across the diagnostic groups.Methods
Rs1006737 was genotyped in 250 individuals (N = 66 BD, 61 SZ and 123 healthy controls), all of Northern European origin, who underwent an fMRI negative faces matching task. Statistical tests were performed with a model correcting for sex, age, diagnostic category and medication status in the total sample, and then in each diagnostic group.Results
In the total sample, carriers of the risk allele had increased activation in the left amygdala. Group-wise analyses showed that this effect was significant in the BD group, but not in the other diagnostic groups. However, there was no significant interaction effect for the risk allele between BD and the other groups.Conclusions
These results indicate that CACNA1C SNP rs1006737 affects amygdala activity during emotional processing across all diagnostic groups. The current findings add to the growing body of knowledge of the pleiotropic effect of this polymorphism, and further support that ion channel dysregulation is involved in the underlying mechanisms of BD and SZ. 相似文献39.
40.
The stereocilia bundle is the mechano-transduction apparatus of the inner ear. In the mammalian cochlea, the stereocilia bundles are situated in the subtectorial space (STS)—a micrometer-thick space between two flat surfaces vibrating relative to each other. Because microstructures vibrating in fluid are subject to high-viscous friction, previous studies considered the STS as the primary place of energy dissipation in the cochlea. Although there have been extensive studies on how metabolic energy is used to compensate the dissipation, much less attention has been paid to the mechanism of energy dissipation. Using a computational model, we investigated the power dissipation in the STS. The model simulates fluid flow around the inner hair cell (IHC) stereocilia bundle. The power dissipation in the STS because of the presence IHC stereocilia increased as the stimulating frequency decreased. Along the axis of the stimulating frequency, there were two asymptotic values of power dissipation. At high frequencies, the power dissipation was determined by the shear friction between the two flat surfaces of the STS. At low frequencies, the power dissipation was dominated by the viscous friction around the IHC stereocilia bundle—the IHC stereocilia increased the STS power dissipation by 50- to 100-fold. There exists a characteristic frequency for STS power dissipation, CFSTS, defined as the frequency where power dissipation drops to one-half of the low frequency value. The IHC stereocilia stiffness and the gap size between the IHC stereocilia and the tectorial membrane determine the characteristic frequency. In addition to the generally assumed shear flow, nonshear STS flow patterns were simulated. Different flow patterns have little effect on the CFSTS. When the mechano-transduction of the IHC was tuned near the vibrating frequency, the active motility of the IHC stereocilia bundle reduced the power dissipation in the STS. 相似文献