Computational prediction of MicroRNAs targeting GABA receptors and experimental verification of miR-181, miR-216 and miR-203 targets in GABA-A receptor

<p>Abstract</p> <p>Background</p> <p>GABA receptors are well known as the inhibitory receptors in the central nervous system and are also found in peripheral tissues. We have previously shown that GABA receptors are involved in lung development and fluid homeostasis. However, the microRNAs that regulate GABA receptors have not yet been identified.</p> <p>Results</p> <p>In this study, we used the online software, TargetScan and miRanda, to query the microRNAs that directly target GABA receptors and then selected some of them to verify experimentally using 3'-UTR reporter assays. Computational approaches predict many microRNA binding sites on the 3'-UTR of GABA_Areceptors, but not on GABA_Creceptors. 3'-UTR reporter assays only verified miR-181, miR-216, and miR-203 as the microRNAs that target GABA receptor α1-subunit among 10 microRNAs tested.</p> <p>Conclusions</p> <p>Our studies reinforce that microRNA target prediction needs to be verified experimentally. The identification of microRNAs that target GABA receptors provides a basis for further studies of post-transcriptional regulation of GABA receptors.</p

ARTICLE IN PRESS +Model HAZMAT-6820; No. of Pages 7 Journal of Hazardous Materials xxx (2007) xxx-xxx Growth response of Zea mays L. in pyrene-copper co-contaminated soil and the fate of pollutants

Abstract Phytoremediation, use of plants for remediation, is an emerging technology for treating heavy metals or a final polishing step for the highlevel organic contamination, and may be suitable for remediation of heavy metal and organic co-contaminated soil. The aim of this study was to investigate the influence of co-contamination on the growth of Zea mays L. and the fate of both heavy metal and organic pollutants, using Cu and pyrene as the model pollutants. Results showed that shoot and root biomass were affected by the copper-pyrene co-contamination, although maize grown in spiked soils showed no outward signs of phytotoxicity. With the initial concentration of 50,100 and 500 mg/kg, pyrene tended to alleviate the inhibition of Cu to Z. mays L. Pyrene in both planted and non-planted soil was greatly decreased at the end of the 4-week culture, accounting for 16-18% of initial extractable concentrations in non-planted soil and 9-14% in planted soil, which indicated that the dissipation of soil pyrene was enhanced in the presence of vegetation probably due to the biodegradation and association with the soil matrix. With the increment of Cu level, residual pyrene in the planted soil tended to increase. The pyrene residual in the presence of high concentration of Cu was even higher in the planted soil than that in the non-planted soil, which suggested that the change of the microbial composition and microbial activity or the modified root physiology under Cu stress was probably unbeneficial to the dissipation of pyrene. A more thorough understanding of the mechanisms by which metals affect the dissipation of organic pollutants in the rhizosphere could provide a much better framework on which to base manipulation. Unlike pyrene, heavy metal copper cannot be degraded. Decontamination of Cu from contaminated soils in this system required the removal of Cu by plants. It was observed that the ability of Cu phytoextraction would be inhibited under co-contamination of high level of pyrene in highly Cu-polluted soil. In the treatment of 400 mg Cu/kg and 500 mg pyrene/kg, the accumulation of Cu was less than half of that in 400 mg Cu/kg treatment

Microsatellite and mitochondrial DNA analysis of the genetic structure of Chinese horseshoe crab (Tachypleus tridentatus) in southeast China coast

Chinese horseshoe crab (Tachypleus tridentatus) is a Xiphosura animal of significant commercial importance and in danger of extinction in China. To better estimate how genetic structure can be used to obtain a conservation perspective of the species, genetic variation was examined in nine locations covering its distributing range in the coast of Chinese mainland using ten nuclear microsatellite DNA loci and mitochondrial DNA control region (CR) sequences. Moderate levels of genetic diversity were detected (expected heterozygosity from microsatellites was 0.635, haplotype diversity from mitochondrial DNA was 0.800) as a whole. Significant genetic differentiation was detected only by mitochondrial DNA (FST = 0.0693, P &lt; 0.01), while microsatellite markers indicated nuclear genetic homogeneity of these locations. Probably, nuclear genetic homogeneity was caused by outbreeding among different groups due to artificial transporting. Very weak genetic differentiation indicates that reintroduction programs of the movement and mixing of horseshoe crab from different locations will result in minimal negative genetic effects. Upon four management units were inferred from the results of CR analysis, accordingly four or more nature reserves should be established to conserve this endangered animal along the Chinese coast. Haplotype network pattern indicated that T. tridentatus population in Chinese coast has undergone historic population expansion and very recent historic population recession. Mismatch distributions analysis also revealed existence of historic demographic expansion.Keywords: Tachypleus tridentatus, microsatellites, mitochondrial DNA, population structure, genetic diversityAfrican Journal of Biotechnology Vol. 12(16), pp. 2088-209

High throughput 16SrRNA gene sequencing reveals the correlation between Propionibacterium acnes and sarcoidosis

Sequences of the unique OTUs. (XLS 3616 kb

A comprehensive AI model development framework for consistent Gleason grading

Background: Artificial Intelligence(AI)-based solutions for Gleason grading hold promise for pathologists, while image quality inconsistency, continuous data integration needs, and limited generalizability hinder their adoption and scalability. Methods: We present a comprehensive digital pathology workflow for AI-assisted Gleason grading. It incorporates A!MagQC (image quality control), A!HistoClouds (cloud-based annotation), Pathologist-AI Interaction (PAI) for continuous model improvement, Trained on Akoya-scanned images only, the model utilizes color augmentation and image appearance migration to address scanner variations. We evaluate it on Whole Slide Images (WSI) from another five scanners and conduct validations with pathologists to assess AI efficacy and PAI. Results: Our model achieves an average F1 score of 0.80 on annotations and 0.71 Quadratic Weighted Kappa on WSIs for Akoya-scanned images. Applying our generalization solution increases the average F1 score for Gleason pattern detection from 0.73 to 0.88 on images from other scanners. The model accelerates Gleason scoring time by 43% while maintaining accuracy. Additionally, PAI improve annotation efficiency by 2.5 times and led to further improvements in model performance. Conclusions: This pipeline represents a notable advancement in AI-assisted Gleason grading for improved consistency, accuracy, and efficiency. Unlike previous methods limited by scanner specificity, our model achieves outstanding performance across diverse scanners. This improvement paves the way for its seamless integration into clinical workflows

The Ratio of Plasma and Urinary 8-oxo-Gsn Could Be a Novel Evaluation Index for Patients with Chronic Kidney Disease

Nucleic acid oxidation plays an important role in the pathophysiology progress of a variety of diseases. 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGsn) and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn), which originate from DNA and RNA oxidation, were the most widely used indicators for oxidative stress. The study investigated the relation between 8-oxo-dGsn, 8-oxo-Gsn, and CKD. 146 patients with CKD were divided into five disease stages, and their fasting blood and morning urine were collected. The levels of 8-oxo-dGsn and 8-oxo-Gsn in plasma and urine were quantified by LC-MS/MS. The ratio of urinary 8-oxo-Gsn to creatinine increased from stages 1 to 4 corresponding to the increased severity of CKD, but it decreased in stage 5. And plasma 8-oxo-Gsn gradually increased with the decline of renal function. In particular, the increased ratio of plasma and urine 8-oxo-Gsn in stage 5 exceeded the concentration of creatinine. This trend was similar to the estimated glomerular filtration rate (eGFR), which indicates that 8-oxo-Gsn could be an appropriate indicator for renal function. Our finding indicates that as the disease progresses, RNA oxidation is increased. The significant increase in the ratio of plasma and urinary 8-oxo-Gsn is a novel evaluation index of end-stage renal disease

Enhanced Notch Activation Is Advantageous but Not Essential for T Cell Lymphomagenesis in Id1 Transgenic Mice

T cell lymphoblastic leukemia (T-ALL) is known to be associated with chromosomal abnormalities that lead to aberrant expression of a number of transcription factors such as TAL1, which dimerizes with basic helix-loop-helix (bHLH) E proteins and inhibits their function. Activated Notch receptors also efficiently induce T cell leukemogenesis in mouse models. Interestingly, gain-of-function mutations or cryptic transcription initiation of the Notch1 gene have been frequently found in both human and mouse T-ALL. However, the correlations between these alterations and overall Notch activities or leukemogenesis have not been thoroughly evaluated. Therefore, we made use of our collection of T cell lymphomas developed in transgenic mice expressing Id1, which like TAL1, inhibits E protein function. By comparing expression levels of Notch target genes in Id1-expressing tumors to those in tumors induced by a constitutively active form of Notch1, N1C, we were able to assess the overall activities of Notch pathways and conclude that the majority of Id1-expressing tumors had elevated Notch function to a varying degree. However, 26% of the Id1-expressing tumors had no evidence of enhanced Notch activation, but that did not delay the onset of tumorigenesis. Furthermore, we examined the genetic or epigenetic alterations thought to contribute to ligand-independent activation or protein stabilization of Notch1 and found that some of the Id1-expressing tumors acquired these changes, but they are not uniformly associated with elevated Notch activities in Id1 tumor samples. In contrast, N1C-expressing tumors do not harbor any PEST domain mutations nor exhibit intragenic transcription initiation. Taken together, it appears that Notch activation provides Id1-expressing tumor cells with selective advantages in growth and survival. However, this may not be absolutely essential for lymphomagenesis in Id1 transgenic mice and additional factors could also cooperate with Id1 to induce T cell lymphoma. Therefore, a broad approach is necessary in designing T-ALL therapy