Acupuncture therapy for preventive and treatment of postoperative nausea and vomiting(PONV), a condition which commonly present after anaesthesia and surgery is a subject of growing interest.
This paper included a systematic review and meta-analysis on the effect of different type of acupuncture and acupoint selection in PONV prevention and treatment.
Randomised controlled trials(RCTs) comparing acupuncture with non-acupuncture treatment were identified from databases PubMed, Cochrane, EBSCO, Ovid, CNKI and Wanfangdata. Meta-analysis on eligible studies was performed using fixed-effects model with RevMan 5.2. Results were expressed as RR for dichotomous data, with 95%CI.
Thirty RCTs, 1276 patients (intervention) and 1258 patients (control) were identified. Meta-analysis showed that PC6 acupuncture significantly reduced the number of cases of early vomiting (postoperative 0-6h) (RR=0.36, 95%CI 0.19,0.71; P=0.003) and nausea (postoperative 0-24h) (RR=0.25, 95%CI 0.10,0.61; P=0.002), but not early nausea (postoperative 0-6h) (RR=0.64, 95%CI 0.34,1.19; P=0.150) and vomiting (postoperative 0-24h) (RR=0.82, 95%CI 0.48,1.38; P=0.450). PC6 acupressure significantly reduced the number of cases of nausea (RR=0.71, 95%CI 0.57,0.87; P=0.001) and vomiting (RR=0.62, 95%CI 0.49,0.80; P=0.000) at postoperative 0-24h. PC6 electro-acupoint stimulation significantly reduced the number of cases of nausea (RR=0.49, 95%CI 0.38,0.63; P<0.000) and vomiting (RR=0.50, 95%CI 0.36,0.70; P<0.000) at postoperative 0-24h. Stimulation of PC6 with other acupoint(s) significantly reduced the number of cases of nausea and vomiting (RR=0.29, 95%CI 0.17,0.49; P<0.000) at postoperative 0-24h. Stimulation of other acupoint(s)(non PC6) also significantly reduced the number of cases of nausea and vomiting (RR=0.63, 95%CI 0.49,0.81; P=0.000) at postoperative 0-24h. However, the quality of study was generally low in studies of PC6 combined with other acupoint(s) and other acupoint(s). Details of blinding were not reported in most reports.
Besides PC6, PC6 combined with other acupoint(s) and other alternative acupoint(s) might be beneficial in prevention and treatment of PONV, the evidence justifies future high-quality studies.
In a number of diseases, certain genes are reported to be strongly methylated and thus can serve as diagnostic markers in many cases. Scientific literature in digital form is an important source of information about methylated genes implicated in particular diseases. The large volume of the electronic text makes it difficult and impractical to search for this information manually.
We developed a novel text mining methodology based on a new concept of position weight matrices (PWMs) for text representation and feature generation. We applied PWMs in conjunction with the document-term matrix to extract with high accuracy associations between methylated genes and diseases from free text. The performance results are based on large manually-classified data. Additionally, we developed a web-tool, DEMGD, which automates extraction of these associations from free text. DEMGD presents the extracted associations in summary tables and full reports in addition to evidence tagging of text with respect to genes, diseases and methylation words. The methodology we developed in this study can be applied to similar association extraction problems from free text.
The new methodology developed in this study allows for efficient identification of associations between concepts. Our method applied to methylated genes in different diseases is implemented as a Web-tool, DEMGD, which is freely available at http://www.cbrc.kaust.edu.sa/demgd/. The data is available for online browsing and download.
Codon usage bias (CUB) results from the complex interplay between translational selection and mutational biases. Current methods for CUB analysis apply heuristics to integrate both components, limiting the depth and scope of CUB analysis as a technique to probe into the evolution and optimization of protein-coding genes. Here we introduce a self-consistent CUB index (scnRCA) that incorporates implicit correction for mutational biases, facilitating exploration of the translational selection component of CUB. We validate this technique using gene expression data and we apply it to a detailed analysis of CUB in the Pseudomonadales. Our results illustrate how the selective enrichment of specific codons among highly expressed genes is preserved in the context of genome-wide shifts in codon frequencies, and how the balance between mutational and translational biases leads to varying definitions of codon optimality. We extend this analysis to other moderate and fast growing bacteria and we provide unified support for the hypothesis that C- and A-ending codons of two-box amino acids, and the U-ending codons of four-box amino acids, are systematically enriched among highly expressed genes across bacteria. The use of an unbiased estimator of CUB allows us to report for the first time that the signature of translational selection is strongly conserved in the Pseudomonadales in spite of drastic changes in genome composition, and extends well beyond the core set of highly optimized genes in each genome. We generalize these results to other moderate and fast growing bacteria, hinting at selection for a universal pattern of gene expression that is conserved and detectable in conserved patterns of codon usage bias.
Tissue plasminogen activator (tPA) administered within 4.5 hours of symptom onset restores cerebral blood flow and promotes neurological recovery of stroke patients. However, the narrow therapeutic time window and the risk of intracerebral hemorrhage after tPA treatment pose major hurdles to its clinical usage. In light of the failures of neuroprotective therapies in clinical trials, emerging concepts suggest that neuroprotection alone without restoration of tissue perfusion and vascular integrity may not be adequate for treatment of acute stroke. Here we review evidence of the use of adjuvant pharmacological agents to extend the therapeutic window for tPA via targeting the neurovascular unit and the underlying mechanisms of the combination therapy in experimental stroke.
HECT ubiquitin ligases are key components of the ubiquitin-proteasome system, which is present in all eukaryotes. In this study, the patterns of emergence of HECT genes in plants are described. Phylogenetic and structural data indicate that viridiplantae have six main HECT subfamilies, which arose before the split that separated green algae from the rest of plants. It is estimated that the common ancestor of all plants contained seven HECT genes. Contrary to what happened in animals, the number of HECT genes has been kept quite constant in all lineages, both in chlorophyta and streptophyta, although evolutionary recent duplications are found in some species. Several of the genes found in plants may have originated very early in eukaryotic evolution, given that they have clear similarities, both in sequence and structure, to animal genes. Finally, in Arabidopsis thaliana, we found significant correlations in the expression patterns of HECT genes and some ancient, broadly expressed genes that belong to a different ubiquitin ligase family, called RBR. These results are discussed in the context of the evolution of the gene families required for ubiquitination in plants.
Elevated intraocular pressure (IOP) is a causative risk factor for the development and progression of glaucoma. Glaucomatous mutations in myocilin (MYOC) damage the trabecular meshwork and elevate IOP in humans and in mice. Animal models of glaucoma are important to discover and better understand molecular pathogenic pathways and to test new glaucoma therapeutics. Although a number of different animal models of glaucoma have been developed and characterized, there are no true models of human primary open angle glaucoma (POAG). The overall goal of this work is to develop the first inducible mouse model of POAG using a human POAG relevant transgene (i.e. mutant MYOC) expression in mouse eyes to elevate IOP and cause pressure induced damage to the optic nerve. Four mouse strains (A/J, BALB/cJ, C57BL/6J, and C3H/HeJ) were used in this study. Ad5.MYOC.Y437H (5 × 107 pfu) was injected intravitreally into one eye, with the uninjected contralateral eye serving as the control eye. Conscious IOP measurements were taken using a TonoLab rebound tonometer. Optic nerve damage was determined by scoring PPD stained optic nerve cross sections. Retinal ganglion cell and superior colliculus damage was assessed by Nissl stain cell counts. Intravitreal administration of viral vector Ad5.MYOC.Y437H caused a prolonged, reproducible, and statistically significant IOP elevation in BALB/cJ, A/J, and C57BL/6J mice. IOPs increased to approximately 25 mm Hg for 8 weeks (p<0.0001). In contrast, the C3H/HeJ mouse strain was resistant to Ad5.MYOC.Y437H induced IOP elevation for the 8-week time period. IOPs were stable (12–15 mm Hg) in the uninjected control eyes. We also determined whether there were any strain differences in pressure-induced optic nerve damage. Even though IOP was similarly elevated in three of the strains tested (BALB/cJ, C57BL/6J, and A/J ) only the A/J strain had considerable and significant optic nerve damage at the end of 8 weeks with optic nerve damage score of 2.64 +/− 0.19 (n=18, p<0.001) in the injected eye. There was no statistical difference in retinal ganglion cell death or superior colliculus damage at the 8-week time point in any of the strains tested. These results demonstrate strain dependent responses to Ad5.MYOC.Y437H-induced ocular hypertension and pressure-induced optic nerve damage.
glaucoma; mouse model; optic nerve; intraocular pressure
Chinese herbal medicine is commonly used as a treatment for benign prostatic hyperplasia (BPH), but its efficacy and safety remain to be examined. To compare the efficacy and adverse events of Chinese herbal medicine alone or used adjuvantly with Western medications for BPH. Two independent reviewers searched the major electronic databases for randomized controlled trials comparing Chinese herbal medicine, either in single or adjuvant use with Western medication, with placebo or Western medication. Relevant journals and grey literature were also hand-searched. The outcome measures included changes in urological symptoms, urodynamic measures, prostate volume and adverse events. The frequency of commonly used herbs was also identified. Out of 13 922 identified citations of publications, 31 studies were included. Eleven studies with a Jadad score ≥3 were selected for meta-analysis. Chinese herbal medicine was superior to Western medication in improving quality of life and reducing prostate volume. The frequency of adverse events in Chinese herbal medicine was similar to that of placebo and less than that of Western medication. The evidence is too weak to support the efficacy of Chinese herbal medicine for BPH due to the poor methodological quality and small number of trials included. The commonly used herbs identified here should provide insights for future clinical practice and research. Larger randomized controlled trials of better quality are needed to truly evaluate the efficacy of Chinese herbal medicine.
benign prostatic hyperplasia (BPH); meta-analysis; review; traditional Chinese medicine
Arctic charr (Salvelinus alpinus) is a highly polymorphic species and in Lake Thingvallavatn, Iceland, four phenotypic morphs have evolved. These differences in morphology, especially in craniofacial structures are already apparent during embryonic development, indicating that genes important in the formation of the craniofacial features are expressed differentially between the morphs. In order to generate tools to examine these expression differences in Arctic charr, the aim of the present study was to identify reference genes for quantitative real-time PCR (qPCR). The specific aim was to select reference genes which are able to detect very small expression differences among different morphs. We selected twelve candidate reference genes from the literature, identified corresponding charr sequences using data derived from transcriptome sequencing (RNA-seq) and examined their expression using qPCR. Many of the candidate reference genes were found to be stably expressed, yet their quality-rank as reference genes varied considerably depending on the type of analysis used. In addition to commonly used software for reference gene validation, we used classical statistics to evaluate expression profiles avoiding a bias for reference genes with similar expression patterns (co-regulation). Based on these analyses we chose three reference genes, ACTB, UB2L3 and IF5A1 for further evaluation. Their consistency was assessed in an expression study of three known craniofacially expressed genes, sparc (or osteonectin), matrix metalloprotease 2 (mmp2) and sox9 (sex-determining region Y box 9 protein) using qPCR in embryo heads derived from four charr groups at three developmental time points. The three reference genes were found to be very suitable for studying expression differences between the morphotypes, enabling robust detection of small relative expression changes during charr development. Further, the results showed that sparc and mmp2 are differentially expressed in embryos of different Arctic charr morphotypes.
Sickle cell disease (SCD) is a fatal monogenic disorder with no effective cure and thus high rates of morbidity and sequelae. Efforts toward discovery of disease modifying drugs and curative strategies can be augmented by leveraging the plethora of information contained in available biomedical literature. To facilitate research in this direction we have developed a resource, Dragon Exploration System for Sickle Cell Disease (DESSCD) (http://cbrc.kaust.edu.sa/desscd/) that aims to promote the easy exploration of SCD-related data.
The Dragon Exploration System (DES), developed based on text mining and complemented by data mining, processed 419,612 MEDLINE abstracts retrieved from a PubMed query using SCD-related keywords. The processed SCD-related data has been made available via the DESSCD web query interface that enables: a/information retrieval using specified concepts, keywords and phrases, and b/the generation of inferred association networks and hypotheses. The usefulness of the system is demonstrated by: a/reproducing a known scientific fact, the “Sickle_Cell_Anemia–Hydroxyurea” association, and b/generating novel and plausible “Sickle_Cell_Anemia–Hydroxyfasudil” hypothesis. A PCT patent (PCT/US12/55042) has been filed for the latter drug repurposing for SCD treatment.
We developed the DESSCD resource dedicated to exploration of text-mined and data-mined information about SCD. No similar SCD-related resource exists. Thus, we anticipate that DESSCD will serve as a valuable tool for physicians and researchers interested in SCD.
Summary: Community curation—harnessing community intelligence in knowledge curation, bears great promise in dealing with the flood of biological knowledge. To exploit the full potential of the scientific community for knowledge curation, multiple biological wikis (bio-wikis) have been built to date. However, none of them have achieved a substantial impact on knowledge curation. One of the major limitations in bio-wikis is insufficient community participation, which is intrinsically because of lack of explicit authorship and thus no credit for community curation. To increase community curation in bio-wikis, here we develop AuthorReward, an extension to MediaWiki, to reward community-curated efforts in knowledge curation. AuthorReward quantifies researchers’ contributions by properly factoring both edit quantity and quality and yields automated explicit authorship according to their quantitative contributions. AuthorReward provides bio-wikis with an authorship metric, helpful to increase community participation in bio-wikis and to achieve community curation of massive biological knowledge.
Supplementary data are available at Bioinformatics online.
Next-generation sequencing (NGS) technologies have been widely used in life sciences. However, several kinds of sequencing artifacts, including low-quality reads and contaminating reads, were found to be quite common in raw sequencing data, which compromise downstream analysis. Therefore, quality control (QC) is essential for raw NGS data. However, although a few NGS data quality control tools are publicly available, there are two limitations: First, the processing speed could not cope with the rapid increase of large data volume. Second, with respect to removing the contaminating reads, none of them could identify contaminating sources de novo, and they rely heavily on prior information of the contaminating species, which is usually not available in advance. Here we report QC-Chain, a fast, accurate and holistic NGS data quality-control method. The tool synergeticly comprised of user-friendly tools for (1) quality assessment and trimming of raw reads using Parallel-QC, a fast read processing tool; (2) identification, quantification and filtration of unknown contamination to get high-quality clean reads. It was optimized based on parallel computation, so the processing speed is significantly higher than other QC methods. Experiments on simulated and real NGS data have shown that reads with low sequencing quality could be identified and filtered. Possible contaminating sources could be identified and quantified de novo, accurately and quickly. Comparison between raw reads and processed reads also showed that subsequent analyses (genome assembly, gene prediction, gene annotation, etc.) results based on processed reads improved significantly in completeness and accuracy. As regard to processing speed, QC-Chain achieves 7–8 time speed-up based on parallel computation as compared to traditional methods. Therefore, QC-Chain is a fast and useful quality control tool for read quality process and de novo contamination filtration of NGS reads, which could significantly facilitate downstream analysis. QC-Chain is publicly available at: http://www.computationalbioenergy.org/qc-chain.html.
Polyporus umbellatus is an important medicinal fungus distributed throughout most area of China. Its wide distribution may have resulted in substantial intraspecific genetic diversity for the fungus, potentially creating variation in its medical value. To date, we know little about the intraspecific genetic diversity of P. umbellatus.
The objective of this research was to assess genetic differences of P. umbellatus from geographically diverse regions of China based on nrDNA ITS and 28S rRNA (LSU, large subunit) sequences. Significant sequence variations in the ITS and LSU sequences were detected. All sclerotial samples were clustered into four clades based on phylogenetic analysis of ITS, LSU and a combined data set of both regions. Heterogeneity of ITS and LSU sequences was detected in 5 and 7 samples respectively. All clone sequences clustered into the same clade except for one LSU clone sequences (from Henan province) which clustered into two clades (Clade I and Clade II). Significant genetic divergence in P. umbellatus was observed and the genetic diversification was greater among sclerotial samples from Shaanxi, Henan and Gansu provinces than among other provinces. Polymorphism of ITS and LSU sequences indicated that in China, P. umbellatus may spread from a center (Shaanxi, Henan and Gansu province) to other regions.
We found sclerotial samples of P. umbellatus contained levels of intraspecific genetic diversity. These findings suggested that P. umbellatus populations in Shaanxi, Henan and Gansu are important resources of genetic diversity and should be conserved accordingly.
Harnessing community intelligence in knowledge curation bears significant promise in dealing with communication and education in the flood of scientific knowledge. As knowledge is accumulated at ever-faster rates, scientific nomenclature, a particular kind of knowledge, is concurrently generated in all kinds of fields. Since nomenclature is a system of terms used to name things in a particular discipline, accurate translation of scientific nomenclature in different languages is of critical importance, not only for communications and collaborations with English-speaking people, but also for knowledge dissemination among people in the non-English-speaking world, particularly young students and researchers. However, it lacks of accuracy and standardization when translating scientific nomenclature from English to other languages, especially for those languages that do not belong to the same language family as English. To address this issue, here we propose for the first time the application of community intelligence in scientific nomenclature management, namely, harnessing collective intelligence for translation of scientific nomenclature from English to other languages. As community intelligence applied to knowledge curation is primarily aided by wiki and Chinese is the native language for about one-fifth of the world’s population, we put the proposed application into practice, by developing a wiki-based English-to-Chinese Scientific Nomenclature Dictionary (ESND; http://esnd.big.ac.cn). ESND is a wiki-based, publicly editable and open-content platform, exploiting the whole power of the scientific community in collectively and collaboratively managing scientific nomenclature. Based on community curation, ESND is capable of achieving accurate, standard, and comprehensive scientific nomenclature, demonstrating a valuable application of community intelligence in knowledge curation.
The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer.
Traditional Chinese medicine (TCM) treatments are often prescribed based on individuals' pattern diagnoses. A systematic review of Chinese and English literatures on TCM pattern differentiation, treatment principle, and pattern-based treatment for insomnia has therefore been conducted. A total of 227 studies, 17916 subjects, and 87 TCM patterns were analyzed. There was a limited consistency in pattern-based TCM treatment of insomnia across practitioners. Except for Gui Pi Tang, An Shen Ding Zhi Wan, and Wen Dan Tang which were used more commonly for deficiency of both the heart and spleen, internal disturbance of phlegm-heat, and qi deficiency of the heart and gallbladder, respectively, the selection of herbal formula for other patterns and pattern-based prescription of individual herbs and acupoints were not consistent. Suanzaoren (Semen Z. spinosae), Fuling (Poria), Yejiaoteng (Caulis P. multiflori), Gancao (Radix Glycyrrhizae), Baishao (Radix P. alba), Shenmen (HT7), Yintang (EX-HN3), Sanyinjiao (SP6), Baihui (GV20), Anmian (EX-HN22), and Sishencong (EX-HN1) were commonly used, but nonspecifically for many patterns. Treatment principles underlying herb and acupoint selection were seldom reported. Although many studies were reviewed, the study quality and diagnostic process were inadequate. More high quality studies are needed to examine the additional benefits of pattern differentiation and pattern-based TCM treatment.
As advances in life sciences and information technology bring profound influences on bioinformatics due to its interdisciplinary nature, bioinformatics is experiencing a new leap-forward from in-house computing infrastructure into utility-supplied cloud computing delivered over the Internet, in order to handle the vast quantities of biological data generated by high-throughput experimental technologies. Albeit relatively new, cloud computing promises to address big data storage and analysis issues in the bioinformatics field. Here we review extant cloud-based services in bioinformatics, classify them into Data as a Service (DaaS), Software as a Service (SaaS), Platform as a Service (PaaS), and Infrastructure as a Service (IaaS), and present our perspectives on the adoption of cloud computing in bioinformatics.
This article was reviewed by Frank Eisenhaber, Igor Zhulin, and Sandor Pongor.
Cloud computing; Bioinformatics; Big data; Data storage; Data analysis
Domain fusion is limited at enzyme one terminus. The issue was explored by swapping a mesophilic Aspergillus niger GH11 xylanase (Xyn) with a hyper-thermophilic Thermotoga maritima glucanase (Glu) to construct two chimeras, Xyn-Glu and Glu-Xyn, with an intention to create thermostable xylanase containing glucanase activity.
When expressed in E. coli BL21(DE3), the two chimeras exhibited bi-functional activities of xylanase and glucanase. The Xyn-Glu Xyn moiety had optimal reaction temperature (Topt) at 50 °C and thermal in-activation half-life (t1/2) at 50 °C for 47.6 min, compared to 47 °C and 17.6 min for the Xyn. The Glu-Xyn Xyn moiety had equivalent Topt to and shorter t1/2 (5.2 min) than the Xyn. Both chimera Glu moieties were more thermostable than the Glu, and the three enzyme Topt values were higher than 96 °C. The Glu-Xyn Glu moiety optimal pH was 5.8, compared to 3.8 for the Xyn-Glu Glu moiety and the Glu. Both chimera two moieties cooperated with each other in degrading substrates.
Domain-swapping created different effects on each moiety properties. Fusing the Glu domain at C-terminus increased the xylanase thermostability, but fusing the Glu domain at N-terminus decreased the xylanase thermostability. Fusing the Xyn domain at either terminus increased the glucanase thermostability, and fusing the Xyn domain at C-terminus shifted the glucanase pH property 2 units higher towards alkaline environments. Fusing a domain at C-terminus contributes more to enzyme catalytic activity; whereas, fusing a bigger domain at N-terminus disturbs enzyme substrate binding affinity.
Xylanase; Glucanase; Domain-swapping; Fusing
Neuromodulation of synaptic plasticity by 17β-estradiol (E2) is thought to influence information processing and storage in the cortex and hippocampus. Because E2 rapidly affects cortical memory and synaptic plasticity, we examined its effects on phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII), extracellular signal-regulated kinase (ERK), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) [AMPA-type glutamate receptor subunit 1 (GluR1 subunit)], all of which are important for the induction and maintenance of synaptic plasticity and memory. Acute E2 treatment resulted in an increased temporal and spatial phosphorylation pattern of CaMKII, ERK, and AMPAR (GluR1 subunit). By using inhibitors, we were able to attribute GluR1 phosphorylation to CaMKII at serine 831, and we also found that E2 treatment increased GluR1 insertion into the surface membrane. Because soluble amyloid-beta (Aβ) oligomers inhibit CaMKII and ERK activation, which is necessary for synaptic plasticity, we also tested E2’s ability to ameliorate Aβ-induced dysfunction of synaptic plasticity. We found that estrogen treatment in neuronal culture, slice culture, and in vivo, ameliorated Aβ oligomer-induced inhibition of CaMKII, ERK, and AMPAR phosphorylation, and also ameliorated the Aβ oligomer-induced reduction of dendritic spine density in a CaMKII-dependent manner. These phosphorylation events are correlated with the early stage of inhibitory avoidance learning, and our data show that E2 improved inhibitory avoidance memory deficits in animals treated with soluble Aβ oligomers. This study identifies E2-induced signaling that attenuates soluble Aβ peptide-mediated dysfunction of pathways in synaptic plasticity.
17β-estradiol; CaMKII; ERK; GluR1; synaptic plasticity
Genetic mutation, selective pressure for translational efficiency and accuracy, level of gene expression, and protein function through natural selection are all believed to lead to codon usage bias (CUB). Therefore, informative measurement of CUB is of fundamental importance to making inferences regarding gene function and genome evolution. However, extant measures of CUB have not fully accounted for the quantitative effect of background nucleotide composition and have not statistically evaluated the significance of CUB in sequence analysis.
Here we propose a novel measure--Codon Deviation Coefficient (CDC)--that provides an informative measurement of CUB and its statistical significance without requiring any prior knowledge. Unlike previous measures, CDC estimates CUB by accounting for background nucleotide compositions tailored to codon positions and adopts the bootstrapping to assess the statistical significance of CUB for any given sequence. We evaluate CDC by examining its effectiveness on simulated sequences and empirical data and show that CDC outperforms extant measures by achieving a more informative estimation of CUB and its statistical significance.
As validated by both simulated and empirical data, CDC provides a highly informative quantification of CUB and its statistical significance, useful for determining comparative magnitudes and patterns of biased codon usage for genes or genomes with diverse sequence compositions.
Codon deviation coefficient; CDC; Codon usage bias; CUB; Statistical significance; Background nucleotide composition; GC content; Purine content; Bootstrapping
When an acupuncture needle is inserted into a designated point on the body and
mechanical or electrical stimulation is delivered, various neural and neuroactive
components are activated. The collection of the activated neural and neuroactive
components distributed in the skin, muscle, and connective tissues surrounding the
inserted needle is defined as a neural acupuncture unit (NAU). The traditionally defined
acupoints represent an anatomical landmark system that indicates local sites where NAUs
may contain relatively dense and concentrated neural and neuroactive components, upon
which acupuncture stimulation would elicit a more efficient therapeutic response. The
NAU-based local mechanisms of biochemical and biophysical reactions play an important
role in acupuncture-induced analgesia. Different properties of NAUs are associated with
different components of needling sensation. There exist several central pathways to
convey NAU-induced acupuncture signals, Electroacupuncture (EA) frequency-specific
neurochemical effects are related to different peripheral and central pathways transmitting
afferent signals from different frequency of NAU stimulation. More widespread and intense
neuroimaging responses of brain regions to acupuncture may be a consequence of more
efficient NAU stimulation modes. The introduction of the conception of NAU provides a
new theoretical approach to interpreting effects and mechanisms of acupuncture in
modern biomedical knowledge framework.
As a key parameter of genome sequence variation, the GC content of bacterial genomes has been investigated for over half a century, and many hypotheses have been put forward to explain this GC content variation and its relationship to other fundamental processes. Previously, we classified eubacteria into dnaE-based groups (the dimeric combination of DNA polymerase III alpha subunits), according to a hypothesis where GC content variation is essentially governed by genome replication and DNA repair mechanisms. Further investigation led to the discovery that two major mutator genes, polC and dnaE2, may be responsible for genomic GC content variation. Consequently, an in-depth analysis was conducted to evaluate various potential intrinsic and extrinsic factors in association with GC content variation among eubacterial genomes.
Mutator genes, especially those with dominant effects on the mutation spectra, are biased towards either GC or AT richness, and they alter genomic GC content in the two opposite directions. Increased bacterial genome size (or gene number) appears to rely on increased genomic GC content; however, it is unclear whether the changes are directly related to certain environmental pressures. Certain environmental and bacteriological features are related to GC content variation, but their trends are more obvious when analyzed under the dnaE-based grouping scheme. Most terrestrial, plant-associated, and nitrogen-fixing bacteria are members of the dnaE1|dnaE2 group, whereas most pathogenic or symbiotic bacteria in insects, and those dwelling in aquatic environments, are largely members of the dnaE1|polV group.
Our studies provide several lines of evidence indicating that DNA polymerase III α subunit and its isoforms participating in either replication (such as polC) or SOS mutagenesis/translesion synthesis (such as dnaE2), play dominant roles in determining GC variability. Other environmental or bacteriological factors, such as genome size, temperature, oxygen requirement, and habitat, either play subsidiary roles or rely indirectly on different mutator genes to fine-tune the GC content. These results provide a comprehensive insight into mechanisms of GC content variation and the robustness of eubacterial genomes in adapting their ever-changing environments over billions of years.
This paper was reviewed by Nicolas Galtier, Adam Eyre-Walker, and Eugene Koonin.
Previous studies suggest that electroacupuncture possesses therapeutic benefits for depressive disorders. The purpose of this study was to determine whether dense cranial electroacupuncture stimulation (DCEAS) could enhance the antidepressant efficacy in the early phase of selective serotonin reuptake inhibitor (SSRI) treatment of major depressive disorder (MDD).
In this single-blind, randomized, controlled study, patients with MDD were randomly assigned to 9-session DCEAS or noninvasive electroacupuncture (n-EA) control procedure in combination with fluoxetine (FLX) for 3 weeks. Clinical outcomes were measured using the 17-item Hamilton Depression Rating Scale (HAMD-17), Clinical Global Impression-severity (CGI-S), and Self-rating Depression Scale (SDS) as well as the response and remission rates.
Seventy-three patients were randomly assigned to n-EA (n = 35) and DCEAS (n = 38), of whom 34 in n-EA and 36 in DCEAS group were analyzed. DCEAS-treated patients displayed a significantly greater reduction from baseline in HAMD-17 scores at Day 3 through Day 21 and in SDS scores at Day 3 and Day 21 compared to patients receiving n-EA. DCEAS intervention also produced a higher rate of clinically significant response compared to n-EA procedure (19.4% (7/36) vs. 8.8% (3/34)). The incidence of adverse events was similar in the two groups.
DCEAS is a safe and effective intervention that augments the antidepressant efficacy. It can be considered as an additional therapy in the early phase of SSRI treatment of depressed patients.
The prevalence and risk of cardiovascular disease increase after menopause in correlation with the progression of abnormality in the serum lipid profile and the deprivation of estrogen. Erxian decoction (EXD), a Chinese medicinal formulation for treating menopausal syndrome, stimulates ovarian estrogen biosynthesis. This study investigates whether EXD improves the serum lipid profile in a menopausal rat model.
Twenty-month-old female Sprague Dawley rats were treated with EXD and its constituent fractions. Premarin was administered for comparison. After eight weeks of treatment, rats were sacrificed and the serum levels of total cholesterol, triglyceride, high-density-lipoprotein cholesterol and low-density-lipoprotein cholesterol were determined. The hepatic protein levels of 3-hydroxy-3-methyl-glutaryl-CoA reductase and low-density-lipoprotein receptor were assessed with Western blot.
The serum levels of total cholesterol and low-density-lipoprotein cholesterol were significantly lower in the EXD-treated group than in the constituent fractions of EXD or premarin groups. However, the serum levels of triglyceride and high-density-lipoprotein cholesterol were not significantly different from the control groups. Results from Western blot suggest that EXD significantly down-regulated the protein level of 3-hydroxy-3-methyl-glutaryl-CoA reductase and up-regulated low-density-lipoprotein receptor. Conclusion EXD improves serum lipid profile in a menopausal rat model through the suppression of the serum levels of total cholesterol and low-density-lipoprotein cholesterol, possibly through the down-regulation of the 3-hydroxy-3-methyl-glutaryl-CoA and up-regulation of the low-density-lipoprotein receptor.
In the molecule of the title compound, C18H22N2O3, the dihydropyrimidinone ring adopts an envelope conformation. The dihedral angle between the phenyl ring and the mean plane through the enamine fragment is 86.04 (7)°. The molecular conformation is stabilized by an intramolecular C—H⋯O hydrogen bond. In the crystal, intermolecular N—H⋯O hydrogen bonds link pairs of molecules into centrosymmetric dimers.