Although acupuncture analgesia is well documented, its mechanisms have not been thoroughly clarified. We previously showed that electroacupuncture (EA) activates supraspinal serotonin- and ...norepinephrine-containing neurones that project to the spinal cord. This study investigates the involvement of spinal alpha(2)-adrenoceptors (α2-ARs) and 5-hydroxytryptamine (serotonin) receptors (5-HTRs) in EA effects on an inflammatory pain rat model.
Inflammatory hyperalgesia was induced by injecting complete Freund's adjuvant (CFA, 0.08 ml) into the plantar surface of one hind paw and assessed by paw withdrawal latency (PWL) to a noxious thermal stimulus. The selective α2a-AR antagonist BRL-44408, α2b-AR antagonist imiloxan hydrochloride, 5-HT2B receptor (5-HT2BR) antagonist SB204741, 5-HT3R antagonist LY278584, or 5-HT1AR antagonists NAN-190 hydrobromide, or WAY-100635 were intrathecally administered 20 min before EA or sham EA, which was given 2 h post-CFA at acupoint GB30.
EA significantly increased PWL compared with sham 7.20 (0.46) vs 5.20 (0.43) s. Pretreatment with α2a-AR 5.35 (0.45) s or 5-HT1AR 5.22 (0.38) s antagonists blocked EA-produced anti-hyperalgesia; α2b-AR, 5-HT2BR, and 5-HT3R antagonist pretreatment did not. Sham plus these antagonists did not significantly change PWL compared with sham plus vehicle, indicating that the antagonists had little effect on PWL. Immunohistochemical staining demonstrated that α2a-ARs are on primary afferents and 5-HT1ARs are localized in N-methyl-d-aspartic acid (NMDA) subunit NR1-containing neurones in the spinal dorsal horn.
The data show that α2a-ARs and 5-HT1ARs are involved in the EA inhibition of inflammatory pain and that the NMDA receptors are involved in EA action.
Nitroimidazole compounds are widely used antibiotics to encounter anaerobic bacterial and parasitic infections. The wide usage of antibiotic drugs became an ecological contaminant which in turn into ...potential monitoring. In this regards, we have designed and developed a new electrochemical sensing probe to monitor an antiprotozoal drug, ornidazole (ODZ), with the aid of a glassy carbon electrode (GCE) integrated with manganese molybdate nanorods (MnMoO4) decorated graphene nanosheets (GNS) hybrid materials that prepared by feasible probe sonochemical method (parameters: 2–4 W, 5 mV amp, 20 kHz). The electrochemical investigations of the developed probe were performed by using rapid scan electrochemical workstations namely cyclic voltammetry (CV) and amperometric (i-t) techniques. The as-prepared MnMoO4/GNS nanocomposite was characterized and its purity of nanocomposite formation was confirmed by various analytical techniques like X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and Raman spectroscopy. In addition to that, the textural morphology of the MnMoO4/GNS nanocomposite was examined with the aid of field emission scanning electron microscopy (FE-SEM) and high-resolution transmission electron microscopy (HR-TEM). The MnMoO4/GNS nanocomposite rotating disk glassy carbon electrode (RDGCE) plays a crucial role in electrochemical detection of ODZ, which results in excellent anti-interference ability, a lower detection limit of 845 pM, massive linear ranges from 10 to 770 nM, and good sensitivity of about 104.62 μA μM−1 cm−2. From the acquired electrochemical studies, we have developed a disposable electrochemical sensor probe using a low-cost screen-printed carbon electrode (SPCE) with MnMoO4/GNS nanocomposite. The MnMoO4/GNS/SPCE are capably employed in real-time sensing of ODZ in water and urine samples. These electrochemical studies revealed the integral new vision on the electrocatalytic performance of the modified SPCE and also shown excellent amplification results in ultra-trace levels.
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•A robust electrochemical sensor probe for ornidazole (ODZ) detection has been reported.•The MnMoO4 decorated graphene nanosheets (GNS) hybrid catalyst prepared by probe sonication method.•The MnMoO4/GNS electrocatalyst showed trace-level detection limit around 845 pM.•The developed sensor was employed for real-time sensing of ODZ in water and urine samples.
Background:
Previous studies have shown that berberine can inhibit glioma progression, although the underlying molecular mechanisms needed to be explored further. The aim of this study was to ...evaluate the suppressive effects of berberine on human glioma cells, and identify the underlying signaling pathways.
Material and Methods:
The cytotoxic effect of different concentrations of berberine against normal human glial cells (HEB) and 4 glioma cell lines was evaluated by the CCK-8 assay. Apoptosis was assayed by flow cytometry. In vitro migration and invasion were analyzed by the wound healing and transwell assays. The expression levels of specific proteins were measured by western blotting and ELISA.
Results:
Berberine significantly inhibited the proliferation of human glioma U-87 cells, and induced apoptosis in the U-87 and LN229 cells by downregulating Bcl-2, and upregulating Bax and caspase-3. In addition, berberine also inhibited migration and invasion of the glioma cells. Furthermore, berberine exerted its effects on the proliferation, migration, invasion, and apoptosis of glioma cells by inhibiting the TGF-β1/SMAD2/3 signaling pathway, and exogenous TGF-β abrogated the pro-apoptotic and anti-oncogenic effects of berberine.
Conclusions:
Berberine inhibits glioma progression by targeting the TGF-β1/SMAD2/3 signaling pathway.
Chromosomal insertions are genomic rearrangements with a chromosome segment inserted into a non-homologous chromosome or a non-adjacent locus on the same chromosome or the other homologue, ...constituting ~2% of nonrecurrent copy-number gains. Little is known about the molecular mechanisms of their formation. We identified 16 individuals with complex insertions among 56,000 individuals tested at Baylor Genetics using clinical array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH). Custom high-density aCGH was performed on 10 individuals with available DNA, and breakpoint junctions were fine-mapped at nucleotide resolution by long-range PCR and DNA sequencing in 6 individuals to glean insights into potential mechanisms of formation. We observed microhomologies and templated insertions at the breakpoint junctions, resembling the breakpoint junction signatures found in complex genomic rearrangements generated by replication-based mechanism(s) with iterative template switches. In addition, we analyzed 5 families with apparently balanced insertion in one parent detected by FISH analysis and found that 3 parents had additional small copy-number variants (CNVs) at one or both sides of the inserting fragments as well as at the inserted sites. We propose that replicative repair can result in interchromosomal complex insertions generated through chromothripsis-like chromoanasynthesis involving two or three chromosomes, and cause a significant fraction of apparently balanced insertions harboring small flanking CNVs.
Concentrations of Dechlorane (Dec) 603 (0.75 ng/g lipid weight (lw); mean) and Dec 602 (0.38 ng/g lw; mean) were quantified in more than 95% of the franciscana (Pontoporia blainvillei) dolphin ...samples, whereas the frequency of detection decreased to 75% for Dechlorane Plus (DP) (1.53 ng/g lw, mean). The presence of Chlordene Plus (CP) was also observed (0.13 ng/g lw, mean) in half of the samples. On the contrary, Dec 604, decachloropentacyclooctadecadiene (aCl10DP), and undecachloropentacyclooctadecadiene (aCl11DP) concentrations were below the limit of quantifications in all cases. To the best of our knowledge, this is the first article reporting the presence of Dec 603, Dec 602, and CP in mammals. For comparative purposes, levels of Mirex, polybrominated diphenyl ethers (PBDEs), and decabromodiphenylethane (DBDPE) are also reported. Considering geographic distribution evaluation together with the strong positive correlations found between DP and PBDEs (r s = 0.63; p < 0.01), highly anthropogenic areas were identified as potential sources of these chemicals in this dolphin species. However, local sources for Dec 602, 603, Mirex, CP, and DBDPE were not found indicating that in this case historical use and/or atmospheric transport and deposition may play an important role in their fate.
Naegleria spp. is a free‐living amoeba that can be found in the natural environment. A number of Naegleria spp. can cause fatal infections in the central nervous system in humans and animals, and the ...most important source of infection is through direct water contact. In this study, water samples from various thermal springs were taken from four thermal spring areas. Naegleria spp. was detected via culture confirmation and molecular taxonomic identification. Among the 60 samples obtained, Naegleria spp. was identified in 26 (43·3%) samples. The identified species included Naegleria australiensis, Naegleria gruberi, Naegleria lovaniensis and Naegleria mexicana. The presence of living Naegleria spp. was significantly associated with elevated pH value in the water sample.
Significance and Impact of Study
In this study, we examined the presence of living Naegleria spp. in
thermal spring waters in south‐eastern Taiwan. Naegleria spp. was isolated and culture‐confirmed from thermal spring water. Naegleria fowleri was not found in all water samples, and Naegleria australiensis
was the most common Naegleria genotype.
Significance and Impact of Study: In this study, we examined the presence of living Naegleria spp. in
thermal spring waters in south‐eastern Taiwan. Naegleria spp. was isolated and culture‐confirmed from thermal spring water. Naegleria fowleri was not found in all water samples, and Naegleria australiensis
was the most common Naegleria genotype.
Alu repetitive elements are known to be major contributors to genome instability by generating Alu-mediated copy-number variants (CNVs). Most of the reported Alu-mediated CNVs are simple deletions ...and duplications, and the mechanism underlying Alu-Alu-mediated rearrangement has been attributed to non-allelic homologous recombination (NAHR). Chromosome 17 at the p13.3 genomic region lacks extensive low-copy repeat architecture; however, it is highly enriched for Alu repetitive elements, with a fraction of 30% of total sequence annotated in the human reference genome, compared with the 10% genome-wide and 18% on chromosome 17. We conducted mechanistic studies of the 17p13.3 CNVs by performing high-density oligonucleotide array comparative genomic hybridization, specifically interrogating the 17p13.3 region with ∼150 bp per probe density; CNV breakpoint junctions were mapped to nucleotide resolution by polymerase chain reaction and Sanger sequencing. Studied rearrangements include 5 interstitial deletions, 14 tandem duplications, 7 terminal deletions and 13 complex genomic rearrangements (CGRs). Within the 17p13.3 region, Alu-Alu-mediated rearrangements were identified in 80% of the interstitial deletions, 46% of the tandem duplications and 50% of the CGRs, indicating that this mechanism was a major contributor for formation of breakpoint junctions. Our studies suggest that Alu repetitive elements facilitate formation of non-recurrent CNVs, CGRs and other structural aberrations of chromosome 17 at p13.3. The common observation of Alu-mediated rearrangement in CGRs and breakpoint junction sequences analysis further demonstrates that this type of mechanism is unlikely attributed to NAHR, but rather may be due to a recombination-coupled DNA replicative repair process.
Results from a few decades of reverberation mapping (RM) studies have revealed a correlation between the radius of the broad-line emitting region (BLR) and the continuum luminosity of active galactic ...nuclei. This "radius-luminosity" relation enables survey-scale black hole mass estimates across cosmic time, using relatively inexpensive single-epoch spectroscopy, rather than intensive RM time monitoring. However, recent results from newer RM campaigns challenge this widely used paradigm, reporting quasar BLR sizes that differ significantly from the previously established radius-luminosity relation. Using simulations of the radius-luminosity relation with the observational parameters of the Sloan Digital Sky Survey Reverberation Mapping (SDSS-RM) project, we find that this difference is not likely due to observational biases. Instead, it appears that previous RM samples were biased to a subset of quasar properties, and the broader parameter space occupied by the SDSS-RM quasar sample has a genuinely wider range of BLR sizes. We examine the correlation between the deviations from the radius-luminosity relation and several quasar parameters; the most significant correlations indicate that the deviations depend on the UV/optical spectral energy distribution and the relative amount of ionizing radiation. Our results indicate that single-epoch black hole mass estimates that do not account for the diversity of quasars in the radius-luminosity relation could be overestimated by an average of ∼0.3 dex.
Abstract
We present reverberation mapping results from the first year of combined spectroscopic and photometric observations of the Sloan Digital Sky Survey Reverberation Mapping Project. We ...successfully recover reverberation time delays between the
g
+
i
band emission and the broad H
β
emission line for a total of 44 quasars, and for the broad H
α
emission line in 18 quasars. Time delays are computed using the
JAVELIN
and
CREAM
software and the traditional interpolated cross-correlation function (ICCF): using well-defined criteria, we report measurements of 32 H
β
and 13 H
α
lags with
JAVELIN
, 42 H
β
and 17 H
α
lags with
CREAM
, and 16 H
β
and eight H
α
lags with the ICCF. Lag values are generally consistent among the three methods, though we typically measure smaller uncertainties with
JAVELIN
and
CREAM
than with the ICCF, given the more physically motivated light curve interpolation and more robust statistical modeling of the former two methods. The median redshift of our H
β
-detected sample of quasars is 0.53, significantly higher than that of the previous reverberation mapping sample. We find that in most objects, the time delay of the H
α
emission is consistent with or slightly longer than that of H
β
. We measure black hole masses using our measured time delays and line widths for these quasars. These black hole mass measurements are mostly consistent with expectations based on the local
–
relationship, and are also consistent with single-epoch black hole mass measurements. This work increases the current sample size of reverberation-mapped active galaxies by about two-thirds and represents the first large sample of reverberation mapping observations beyond the local universe (
z
< 0.3).
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