MirGeneDB 2.1: toward a complete sampling of all major animal phyla.

We describe an update of MirGeneDB, the manually curated microRNA gene database. Adhering to uniform and consistent criteria for microRNA annotation and nomenclature, we substantially expanded MirGeneDB with 30 additional species representing previously missing metazoan phyla such as sponges, jellyfish, rotifers and flatworms. MirGeneDB 2.1 now consists of 75 species spanning over ∼800 million years of animal evolution, and contains a total number of 16 670 microRNAs from 1549 families. Over 6000 microRNAs were added in this update using ∼550 datasets with ∼7.5 billion sequencing reads. By adding new phylogenetically important species, especially those relevant for the study of whole genome duplication events, and through updating evolutionary nodes of origin for many families and genes, we were able to substantially refine our nomenclature system. All changes are traceable in the specifically developed MirGeneDB version tracker. The performance of read-pages is improved and microRNA expression matrices for all tissues and species are now also downloadable. Altogether, this update represents a significant step toward a complete sampling of all major metazoan phyla, and a widely needed foundation for comparative microRNA genomics and transcriptomics studies. MirGeneDB 2.1 is part of RNAcentral and Elixir Norway, publicly and freely available at http://www.mirgenedb.org/.

Role of NF-κB in cardiac changes of obstructive sleep apnoea rabbits treated by mandibular advancement device.

BACKGROUND: Obstructive sleep apnoea (OSA) is an independent risk factor for cardiovascular diseases. We aimed to investigate the role of nuclear factor-kappa B (NF-κB) in the changes of cardiac structures in OSA rabbits treated by mandibular advancement device (MAD). METHODS: Eighteen male New Zealand white rabbits aged 6 months were randomly divided into three groups: control group, group OSA and group MAD. Hyaluronate gel was injected into the soft palate of the rabbits in group OSA and group MAD to induce OSA. The cone beam computer tomography (CBCT) of the upper airway and polysomnography (PSG) was performed to ensure successful modelling. CBCT and PSG were applied again to detect the effects of MAD treatment. All animals were induced to sleep in a supine position for 4-6 h a day for 8 weeks. Then the levels of NF-κB, Interleukin 6 (IL-6), Interleukin 10 (IL-10) and the proportion of myocardial fibrosis (MF) were detected. RESULTS: The higher activation of NF-κB, IL-6 and IL-10 were found in the OSA group than in the control group, leading to the increase of collagen fibres compared with the control group. Furthermore, the apnoea-hypopnea index (AHI) was positively correlated with the above factors. There were no significant differences between group MAD and the control group. CONCLUSION: The NF-κB pathway was activated in the myocardium of OSA rabbits, which accelerated the development of MF. Early application of MAD could reduce the activation of NF-κB in the myocardium and prevent the development of MF.

A mandibular advancement device attenuates the abnormal morphology and function of mitochondria from the genioglossus in obstructive sleep apnea-hypopnea syndrome rabbits.

BACKGROUND: Obstructive sleep apnea hypopnea syndrome (OSAHS) is a serious and potentially life-threatening disease. Mandibular advancement device (MAD) has the characteristics of non-invasive, comfortable, portable and low-cost, making it the preferred treatment for mild-to-moderate OSAHS. Our previous studies found that abnormal contractility and fibre type distribution of the genioglossus could be caused by OSAHS. However, whether the mitochondria participate in these tissue changes is unclear. The effect of MAD treatment on the mitochondria of the genioglossus in OSAHS is also uncertain. OBJECTIVE: To examine the morphology and function of mitochondria from the genioglossus in a rabbit model of obstructive sleep apnea-hypopnea syndrome (OSAHS), as well as these factors after insertion of a mandibular advancement device (MAD). METHODS: Thirty male New Zealand white rabbits were randomised into three groups: control, OSAHS and MAD, with 10 rabbits in each group. Animals in Group OSAHS and Group MAD were induced to develop OSAHS by injection of gel into the submucosal muscular layer of the soft palate. The rabbits in Group MAD were fitted with a MAD. The animals in the control group were not treated. Further, polysomnography (PSG) and cone-beam computed tomography (CBCT) scan were used to measure MAD effectiveness. CBCT of the upper airway and PSG suggested that MAD was effective. Rabbits in the three groups were induced to sleep for 4-6 h per day for eight consecutive weeks. The genioglossus was harvested and detected by optical microscopy and transmission electron microscopy. The mitochondrial membrane potential was determined by laser confocal microscopy and flow cytometry. Mitochondrial complex I and IV activities were detected by mitochondrial complex assay kits. RESULTS: OSAHS-like symptoms were induced successfully in Group OSAHS and rescued by MAD treatment. The relative values of the mitochondrial membrane potential, mitochondrial complex I activity and complex IV activity were significantly lower in Group OSAHS than in the control group; however, there was no significant difference between Group MAD and the control group. The OSAHS-induced injury and the dysfunctional mitochondria of the genioglossus muscle were reduced by MAD treatment. CONCLUSION: Damaged mitochondrial structure and function were induced by OSAHS and could be attenuated by MAD treatment.

Targeting m6A binding protein YTHDFs for cancer therapy.

N6-methyladenosine (m6A) is the most common mRNA modification in mammalians. The function and dynamic regulation of m6A depends on the "writer", "readers" and "erasers". YT521-B homology domain family (YTHDF) is a class of m6A binding proteins, including YTHDF1, YTHDF2 and YTHDF3. In recent years, the modification of m6A and the molecular mechanism of YTHDFs have been further understood. Growing evidence has shown that YTHDFs participate in multifarious bioprocesses, particularly tumorigenesis. In this review, we summarized the structural characteristics of YTHDFs, the regulation of mRNA by YTHDFs, the role of YTHDF proteins in human cancers and inhibition of YTHDFs.

Highly Conjugated Graphitic Carbon Nitride Nanofoam for Photocatalytic Hydrogen Evolution.

As a metal-free photocatalyst, graphitic carbon nitride (g-CN) shows great potential for photocatalytic water splitting, although its performance is significantly limited by structural defects due to incomplete polymerization. In the present work, we successfully synthesize highly conjugated g-CN nanofoam through an iodide substitution technique. The product possesses a high polymerization degree, low defect density, and large specific surface area; as a result, it achieves a hydrogen evolution rate of 9.06 mmol h-1 g-1 under visible light irradiation, with an apparent quantum efficiency (AQE) of 18.9% at 420 nm. Experimental analysis and theoretical calculations demonstrate that the recombination of photogenerated carriers at C-NHx defects was effectively depressed in the nanofoam, giving rise to the high photocatalytic activity.

MirGeneDB 2.0: the metazoan microRNA complement.

Small non-coding RNAs have gained substantial attention due to their roles in animal development and human disorders. Among them, microRNAs are special because individual gene sequences are conserved across the animal kingdom. In addition, unique and mechanistically well understood features can clearly distinguish bona fide miRNAs from the myriad other small RNAs generated by cells. However, making this distinction is not a common practice and, thus, not surprisingly, the heterogeneous quality of available miRNA complements has become a major concern in microRNA research. We addressed this by extensively expanding our curated microRNA gene database - MirGeneDB - to 45 organisms, encompassing a wide phylogenetic swath of animal evolution. By consistently annotating and naming 10,899 microRNA genes in these organisms, we show that previous microRNA annotations contained not only many false positives, but surprisingly lacked >2000 bona fide microRNAs. Indeed, curated microRNA complements of closely related organisms are very similar and can be used to reconstruct ancestral miRNA repertoires. MirGeneDB represents a robust platform for microRNA-based research, providing deeper and more significant insights into the biology and evolution of miRNAs as well as biomedical and biomarker research. MirGeneDB is publicly and freely available at http://mirgenedb.org/.

Characterization of a major quantitative trait locus on the short arm of chromosome 4B for spike number per unit area in common wheat (Triticum aestivum L.).

KEY MESSAGE: An InDel marker closely linked with a major and stable quantitative trait locus (QTL) on chromosome 4BS, QSnpa.cau-4B, controlling spike number per unit area will benefit wheat yield improvement. Spike number per unit area (SNPA) is an essential yield-related trait, and analyzing its genetic basis is important for cultivar improvement in wheat (Triticum aestivum L.). In this study, we used the F2 population derived from a cross between two wheat accessions displaying significant differences in SNPA to perform quantitative trait locus (QTL) analysis. Through bulked segregant analysis, a major and stable QTL that explained 18.11-82.11% of the phenotypic variation was identified on chromosome 4BS. The QTL interval was validated using F4:5 and F6:7 families and narrowed it to a 24.91-38.36 Mb region of chromosome 4BS according to the 'Chinese Spring' reference genome sequence. In this region, variations in 16 genes caused amino acid changes and three genes were present in only one parent. Among these, we annotated a gene orthologous to TB1 in maize (Zea mays), namely TraesCS4B01G042700, which carried a 44-bp deletion in its promoter in the higher-SNPA parent. An InDel marker based on the insertion/deletion polymorphism was designed and used to diagnose the allelic distribution within a natural population. The frequency of the 44-bp deletion allele associated with higher SNPA was relatively low (13.24%), implying that this favorable allele has not been widely utilized and could be valuable for wheat yield improvement. In summary, we identified a major and stable QTL for SNPA and developed a diagnostic marker for the more-spiked trait, which will be beneficial for molecular-assisted breeding in wheat.

Ultrafast Parallelized Microfluidic Platform for Antimicrobial Susceptibility Testing of Gram Positive and Negative Bacteria.

Antimicrobial susceptibility testing (AST) is an essential diagnostic procedure to determine the correct course of treatment for various types of pathogen infections. Patients are treated with broad spectrum antibiotics until AST results become available, which has contributed to the emergence of multidrug resistant bacteria worldwide. Conventional AST methods require 16-24 h to assess sensitivity of the bacteria to a given drug and establish its minimum inhibitory concentration (MIC). A rapid AST assay can assist clinicians in making an informed choice of targeted therapy and avoid unnecessary overprescription. Here, we have developed a highly parallelized droplet microfluidic platform that can screen four antibiotics/pathogens simultaneously and assess antibiotic sensitivity in 15-30 min. The device consists of four integrated microdroplet arrays, each hosting over 8000 docking sites, which can be operated individually or jointly for greater flexibility of operation. Small numbers (1-4) of bacterial cells were entrapped in droplets of 110 pL volume and monitored dynamically over 2 h. This imaging-based AST approach was used to determine the growth rates of four types of clinically relevant bacteria known to cause urinary tract infection (UTI) in millions of patients. We quantified doubling times of both Gram positive ( Staphylococcus aureus, Enterococcus faecalis) and Gram negative bacteria (e.g., Escherichia coli, Klebsiella pneumoniae) with varying levels of antibiotic resistance. Six concentrations of bactericidal and bacteriostatic antibiotics (oxacillin and tetracycline, respectively) were tested to determine the MIC of the strains as well as the heterogeneity in growth profiles of bacteria at single cell resolution. The MIC determined from phenotypic analysis in droplets matched the MIC obtained from broth microdilution method for all strains. The advantages of the proposed droplet-based AST, including rapid drug sensitivity response, morphological analysis, and heterogeneity in antibiotic-resistance profiles, make it an excellent alternative to standard phenotypic AST with potential applications in clinical diagnostics and point of care testing.

Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts.

miRNAs are small 22-nucleotide RNAs that can post-transcriptionally regulate gene expression. It has been proposed that dietary plant miRNAs can enter the human bloodstream and regulate host transcripts; however, these findings have been widely disputed. We here conduct the first comprehensive meta-study in the field, surveying the presence and abundances of cross-species miRNAs (xenomiRs) in 824 sequencing data sets from various human tissues and body fluids. We find that xenomiRs are commonly present in tissues (17%) and body fluids (69%); however, the abundances are low, comprising 0.001% of host human miRNA counts. Further, we do not detect a significant enrichment of xenomiRs in sequencing data originating from tissues and body fluids that are exposed to dietary intake (such as liver). Likewise, there is no significant depletion of xenomiRs in tissues and body fluids that are relatively separated from the main bloodstream (such as brain and cerebro-spinal fluids). Interestingly, the majority (81%) of body fluid xenomiRs stem from rodents, which are a rare human dietary contribution but common laboratory animals. Body fluid samples from the same studies tend to group together when clustered by xenomiR compositions, suggesting technical batch effects. Last, we performed carefully designed and controlled animal feeding studies, in which we detected no transfer of plant miRNAs into rat blood, or bovine milk sequences into piglet blood. In summary, our comprehensive computational and experimental results indicate that xenomiRs originate from technical artifacts rather than dietary intake.

Bayesian Compressive Sensing Based Optimized Node Selection Scheme in Underwater Sensor Networks.

Information acquisition in underwater sensor networks is usually limited by energy and bandwidth. Fortunately, the received signal can be represented sparsely on some basis. Therefore, a compressed sensing method can be used to collect the information by selecting a subset of the total sensor nodes. The conventional compressed sensing scheme is to select some sensor nodes randomly. The network lifetime and the correlation of sensor nodes are not considered. Therefore, it is significant to adjust the sensor node selection scheme according to these factors for the superior performance. In this paper, an optimized sensor node selection scheme is given based on Bayesian estimation theory. The advantage of Bayesian estimation is to give the closed-form expression of posterior density function and error covariance matrix. The proposed optimization problem first aims at minimizing the mean square error (MSE) of Bayesian estimation based on a given error covariance matrix. Then, the non-convex optimization problem is transformed as a convex semidefinite programming problem by relaxing the constraints. Finally, the residual energy of each sensor node is taken into account as a constraint in the optimization problem. Simulation results demonstrate that the proposed scheme has better performance than a conventional compressed sensing scheme.

Determination of Lead with a Copper-Based Electrochemical Sensor.

This work demonstrates determination of lead (Pb) in surface water samples using a low-cost copper (Cu)-based electrochemical sensor. Heavy metals require careful monitoring due to their toxicity, yet current methods are too complex or bulky for point-of-care (POC) use. Electrochemistry offers a convenient alternative for metal determination, but the traditional electrodes, such as carbon or gold/platinum, are costly and difficult to microfabricate. Our copper-based sensor features a low-cost electrode material-copper-that offers simple fabrication and competitive performance in electrochemical detection. For anodic stripping voltammetry (ASV) of Pb, our sensor shows 21 nM (4.4 ppb) limit of detection, resistance to interfering metals such as cadmium (Cd) and zinc (Zn), and stable response in natural water samples with minimum sample pretreatment. These results suggest this electrochemical sensor is suitable for environmental and potentially biological applications, where accurate and rapid, yet inexpensive, on-site monitoring is necessary.

The acute effects of ultraviolet radiation on the blood transcriptome are independent of plasma 25OHD3.

The molecular basis of many health outcomes attributed to solar ultraviolet radiation (UVR) is unknown. We tested the hypothesis that they may originate from transcriptional changes in blood cells. This was determined by assessing the effect of fluorescent solar simulated radiation (FSSR) on the transcriptional profile of peripheral blood pre- and 6h, 24h and 48h post-exposure in nine healthy volunteers. Expression of 20 genes was down-regulated and one was up-regulated at 6h after FSSR. All recovered to baseline expression at 24h or 48h. These genes have been associated with immune regulation, cancer and blood pressure; health effects attributed to vitamin D via solar UVR exposure. Plasma 25-hydroxyvitamin D3 [25OHD3] levels increased over time after FSSR and were maximal at 48h. The increase was more pronounced in participants with low basal 25OHD3 levels. Mediation analyses suggested that changes in gene expression due to FSSR were independent of 25OHD3 and blood cell subpopulations.

Bare and Polymer-Coated Indium Tin Oxide as Working Electrodes for Manganese Cathodic Stripping Voltammetry.

Though an essential metal in the body, manganese (Mn) has a number of health implications when found in excess that are magnified by chronic exposure. These health complications include neurotoxicity, memory loss, infertility in males, and development of a neurologic psychiatric disorder, manganism. Thus, trace detection in environmental samples is increasingly important. Few electrode materials are able to reach the negative reductive potential of Mn required for anodic stripping voltammetry (ASV), so cathodic stripping voltammetry (CSV) has been shown to be a viable alternative. We demonstrate Mn CSV using an indium tin oxide (ITO) working electrode both bare and coated with a sulfonated charge selective polymer film, polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene-sulfonate (SSEBS). ITO itself proved to be an excellent electrode material for Mn CSV, achieving a calculated detection limit of 5 nM (0.3 ppb) with a deposition time of 3 min. Coating the ITO with the SSEBS polymer was found to increase the sensitivity and lower the detection limit to 1 nM (0.06 ppb). This polymer modified electrode offers excellent selectivity for Mn as no interferences were observed from other metal ions tested (Zn(2+), Cd(2+), Pb(2+), In(3+), Sb(3+), Al(3+), Ba(2+), Co(2+), Cu(2+), Ni(3+), Bi(3+), and Sn(2+)) except Fe(2+), which was found to interfere with the analytical signal for Mn(2+) at a ratio 20:1 (Fe(2+)/Mn(2+)). The applicability of this procedure to the analysis of tap, river, and pond water samples was demonstrated. This simple, sensitive analytical method using ITO and SSEBS-ITO could be applied to a number of electroactive transition metals detectable by CSV.

Roles of NMDA and dopamine in food-foraging decision-making strategies of rats in the social setting.

BACKGROUND: In highly complex social settings, an animal's motivational drive to pursue an object depends not only on the intrinsic properties of the object, but also on whether the decision-making animal perceives an object as being the most desirable among others. Mimetic desire refers to a subject's preference for objects already possessed by another subject. To date, there are no appropriate animal models for studying whether mimetic desire is at play in guiding the decision-making process. Furthermore, the neuropharmacological bases of decision-making processes are not well understood. In this study, we used an animal model (rat) to investigate a novel food-foraging paradigm for decision-making, with or without a mimetic desire paradigm. RESULTS: Faced with the choice of foraging in a competitive environment, rats preferred foraging for the desirable object, indicating the rats' ability for decision-making. Notably, treatment with the non-competitive N-methyl-D-aspartate receptor antagonist MK-801, but not with the dopamine D1 or D2 receptor antagonists, SCH23390 and haloperidol, respectively, suppressed the food foraging preference when there was a competing resident rat in the cage. None of these three antagonists affected the food-foraging preference for palatable food. Moreover, MK-801 and SCH23390, but not haloperidol, were able to abolish the desirable environment effect on standard food-foraging activities in complex social settings. CONCLUSIONS: These results highlight the concept that mimetic desire exerts a powerful influence on food-foraging decision-making in rats and, further, illustrate the various roles of the glutamatergic and dopaminergic systems in mediating these processes.

Disposable copper-based electrochemical sensor for anodic stripping voltammetry.

In this work, we report the first copper-based point-of-care sensor for electrochemical measurements demonstrated by zinc determination in blood serum. Heavy metals require careful monitoring, yet current methods are too complex for a point-of-care system. Electrochemistry offers a simple approach to metal detection on the microscale, but traditional carbon, gold (Au), or platinum (Pt) electrodes are difficult or expensive to microfabricate, preventing widespread use. Our sensor features a new low-cost electrode material, copper, which offers simple fabrication and compatibility with microfabrication and PCB processing, while maintaining competitive performance in electrochemical detection. Anodic stripping voltammetry of zinc using our new copper-based sensors exhibited a 140 nM (9.0 ppb) limit of detection (calculated) and sensitivity greater than 1 µA/µM in the acetate buffer. The sensor was also able to determine zinc in a bovine serum extract, and the results were verified with independent sensor measurements. These results demonstrate the advantageous qualities of this lab-on-a-chip electrochemical sensor for clinical applications, which include a small sample volume (µL scale), reduced cost, short response time, and high accuracy at low concentrations of analyte.

Copper-based electrochemical sensor with palladium electrode for cathodic stripping voltammetry of manganese.

In this work, we report on the development of a palladium-based, microfabricated point-of-care electrochemical sensor for the determination of manganese using square wave cathodic stripping voltammetry. Heavy metals require careful monitoring, yet current methods are too complex for a point-of-care system. Voltammetry offers an attractive approach to metal detection on the microscale, but traditional carbon, gold, or platinum electrodes are difficult or expensive to microfabricate, preventing widespread use. Our sensor uses palladium working and auxiliary electrodes and integrates them with a copper-based reference electrode for simple fabrication and compatibility with microfabrication and printed circuit board processing, while maintaining competitive performance in electrochemical detection. Copper electrodes were prepared on glass substrate using a combination of microfabrication procedures followed by electrodeposition of palladium. The disposable sensor system was formed by bonding a poly(dimethylsiloxane) (PDMS) well to the glass substrate. Cathodic stripping voltammetry of manganese using our new disposable palladium-based sensors exhibited 334 nM (18.3 ppb) limit of detection in borate buffer. The sensor was used to demonstrate manganese determination in natural water samples from a pond in Burnet Woods, located in Cincinnati, OH, and the Ohio River.

Improving Reproducibility of Lab-on-a-Chip Sensor with Bismuth Working Electrode for Determining Zn in Serum by Anodic Stripping Voltammetry.

This work reports on the continuing development of a lab-on-a-chip electrochemical sensor for determination of zinc in blood serum using square wave anodic stripping voltammetry. The microscale sensor consists of a three electrode system, including an environmentally friendly bismuth working electrode, an integrated silver/silver chloride reference electrode, and a gold auxiliary electrode. The sensor demonstrates a linear response in 0.1 M acetate buffer at pH 6 for zinc concentrations in the 1-30 µM range. By optimizing bismuth film deposition and better control of the fabrication process, repeatability of the sensor was improved, reducing variability from 42% to <2%. Through optimization of electrolyte and stripping voltammetry parameters, limit of detection was greatly improved to 60 nM. The optimized sensor was also able to measure zinc in the extracted blood serum. Ultimately, with integrated sample preparation, the sensor will permit rapid (min) measurements of zinc from a sub-mL sample (a few drops of blood) for clinical applications.

Analysis of the quantity and quality of published randomised controlled trials related to injury prevention from 2001 to 2010 in China.

OBJECTIVE: To report the quantity and quality of published randomised controlled trails (RCT) on injury prevention in China. DESIGN: Bibliometric analysis. SETTING: China, 2001-2010. DATA SOURCES: The published RCTs that were indexed by four domestic electronic databases and two international databases between 1 January 2001 and 31 December 2010. MAIN OUTCOME MEASURES: Numbers and proportions of published RCTs and those that did not report or specify the quality items recommended by Cochrane Handbook for Systematic Reviews of Intervention V.5.0.0. RESULTS: Of 4834 publications of injury prevention, 25 RCTs with 55,431 participants were identified. One study had no full text. Twenty-three RCTs were published in Chinese language. All 25 studies chose education as the intervention, including 19 studies using education as single intervention and 6 studies using education as a part of combined intervention. Eighteen of 19 studies that used injury incidence rate as the primary outcome measure; 10 studies reported 24-59% reductions in injury incidence rate in the intervention group, and 8 studies reported 24-76% rate difference between the intervention group and the control group after the implementation of intervention. Only 1 study reported no significant difference. The other 6 studies only reported improvements in knowledge, attitude and practice/behaviour. None of 24 studies with full text included the information of 'allocation concealment', 'blinding' and 'free of early stopping bias'. CONCLUSIONS: The value of 25 published RCTs cannot be determined due to the lack of quality information. More high-quality RCTs need to be performed in the future.

IDMA-based MAC protocol for satellite networks with consideration on channel quality.

In order to overcome the shortcomings of existing medium access control (MAC) protocols based on TDMA or CDMA in satellite networks, interleave division multiple access (IDMA) technique is introduced into satellite communication networks. Therefore, a novel wide-band IDMA MAC protocol based on channel quality is proposed in this paper, consisting of a dynamic power allocation algorithm, a rate adaptation algorithm, and a call admission control (CAC) scheme. Firstly, the power allocation algorithm combining the technique of IDMA SINR-evolution and channel quality prediction is developed to guarantee high power efficiency even in terrible channel conditions. Secondly, the effective rate adaptation algorithm, based on accurate channel information per timeslot and by the means of rate degradation, can be realized. What is more, based on channel quality prediction, the CAC scheme, combining the new power allocation algorithm, rate scheduling, and buffering strategies together, is proposed for the emerging IDMA systems, which can support a variety of traffic types, and offering quality of service (QoS) requirements corresponding to different priority levels. Simulation results show that the new wide-band IDMA MAC protocol can make accurate estimation of available resource considering the effect of multiuser detection (MUD) and QoS requirements of multimedia traffic, leading to low outage probability as well as high overall system throughput.