The prokaryotic pangenome partitions genes into core and dispensable genes. The order of core genes, albeit assumed to be stable under selection in general, is frequently interrupted by horizontal gene transfer and rearrangement, but how a core-gene-defined genome maintains its stability or flexibility remains to be investigated. Based on data from 30 species, including 425 genomes from six phyla, we grouped core genes into syntenic blocks in the context of a pangenome according to their stability across multiple isolates. A subset of the core genes, often species specific and lineage associated, formed a core-gene-defined genome organizational framework (cGOF). Such cGOFs are either single segmental (one-third of the species analyzed) or multisegmental (the rest). Multisegment cGOFs were further classified into symmetric or asymmetric according to segment orientations toward the origin-terminus axis. The cGOFs in Gram-positive species are exclusively symmetric and often reversible in orientation, as opposed to those of the Gram-negative bacteria, which are all asymmetric and irreversible. Meanwhile, all species showing strong strand-biased gene distribution contain symmetric cGOFs and often specific DnaE (α subunit of DNA polymerase III) isoforms. Furthermore, functional evaluations revealed that cGOF genes are hub associated with regard to cellular activities, and the stability of cGOF provides efficient indexes for scaffold orientation as demonstrated by assembling virtual and empirical genome drafts. cGOFs show species specificity, and the symmetry of multisegmental cGOFs is conserved among taxa and constrained by DNA polymerase-centric strand-biased gene distribution. The definition of species-specific cGOFs provides powerful guidance for genome assembly and other structure-based analysis.
Prokaryotic genomes are frequently interrupted by horizontal gene transfer (HGT) and rearrangement. To know whether there is a set of genes not only conserved in position among isolates but also functionally essential for a given species and to further evaluate the stability or flexibility of such genome structures across lineages are of importance. Based on a large number of multi-isolate pangenomic data, our analysis reveals that a subset of core genes is organized into a core-gene-defined genome organizational framework, or cGOF. Furthermore, the lineage-associated cGOFs among Gram-positive and Gram-negative bacteria behave differently: the former, composed of 2 to 4 segments, have their fragments symmetrically rearranged around the origin-terminus axis, whereas the latter show more complex segmentation and are partitioned asymmetrically into chromosomal structures. The definition of cGOFs provides new insights into prokaryotic genome organization and efficient guidance for genome assembly and analysis.
The FIP1-like-1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRα) fusion oncogene is the driver factor in a subset of patients with hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL). Most FIP1L1-PDGFRα-positive patients respond well to the tyrosine kinase inhibitor (TKI) imatinib. Resistance to imatinib in HES/CEL has been described mainly due to the T674I mutation in FIP1L1-PDGFRα, which is homologous to the imatinib-resistant T315I mutation in BCR-ABL. Development of novel TKIs is imperative to overcome resistance to imatinib. We synthesized S116836, a novel TKI. In this study, we evaluated the antitumor activity of S116836 in FIP1L1-PDGFRα-expressing cells. The results showed that S116836 potently inhibited PDGFRα and its downstream signaling molecules such as STAT3, AKT, and Erk1/2. S116836 effectively inhibited the growth of the WT and T674I FIP1L1-PDGFRα-expressing neoplastic cells in vitro and in nude mouse xenografts. Moreover, S116836 induced intrinsic pathway of apoptosis as well as the death receptor pathway, coincided with up-regulation of the proapoptotic BH3-only protein Bim-EL through the Erk1/2 pathway. In conclusion, S116836 is active against WT and T674I FIP1L1-PDGFRα-expressing cells, and may be a prospective agent for the treatment of HES/CEL.
PDGFRα; T674I; tyrosine kinase inhibitor; imatinib; resistance; S116836; apoptosis; Bim
We report a novel hybrid material Na2Mo4O13/α-MoO3 as highly efficient catalytic wet air oxidation (CWAO) catalyst, which showed the highest ever activity at room temperature and atmosphere pressure for the degradation of cationic red GTL. SEM and TEM analyses indicated that this hybrid catalyst has bamboo-shaped nanofiber morphology. In view of practical applications, the influence of some key parameters including operation temperature, catalyst calcination temperature, and the volume of dye wastewater have been optimized. The mechanism for the superior catalytic performance was investigated. XRD, XPS, and ESR suggested the Na2Mo4O13/α-MoO3 hybrid catalyst possesses more O2− ions in the oxygen deficient regions than neat α-MoO3, promoting the formation of active ·OH radicals and resulting in a higher activity. Considering the facile preparation and its superior activity, this novel catalyst is promising for practical dye wastewater treatment.
Pulmonary hypertensive remodeling is characterized by excessive proliferation, migration, and proinflammatory activation of adventitial fibroblasts. In culture, fibroblasts maintain a similar activated phenotype. The mechanisms responsible for generation/maintenance of this phenotype remain unknown.
We hypothesized that aberrant expression of microRNA-124 (miR-124) regulates this activated fibroblast phenotype and sought to determine the signaling pathways through which miR-124 exerts effects.
Methods and Results
We detected significant decreases in miR-124 expression in fibroblasts isolated from calves and humans with severe pulmonary hypertension. Overexpression of miR-124 by mimic transfection significantly attenuated proliferation, migration, and monocyte chemotactic protein-1 expression of hypertensive fibroblasts, whereas anti–miR-124 treatment of control fibroblasts resulted in their increased proliferation, migration, and monocyte chemotactic protein-1 expression. Furthermore, the alternative splicing factor, polypyrimidine tract–binding protein 1, was shown to be a direct target of miR-124 and to be upregulated both in vivo and in vitro in bovine and human pulmonary hypertensive fibroblasts. The effects of miR-124 on fibroblast proliferation were mediated via direct binding to the 3′ untranslated region of polypyrimidine tract–binding protein 1 and subsequent regulation of Notch1/phosphatase and tensin homolog/FOXO3/p21Cip1 and p27Kip1 signaling. We showed that miR-124 directly regulates monocyte chemotactic protein-1 expression in pulmonary hypertension/idiopathic pulmonary arterial hypertension fibroblasts. Furthermore, we demonstrated that miR-124 expression is suppressed by histone deacetylases and that treatment of hypertensive fibroblasts with histone deacetylase inhibitors increased miR-124 expression and decreased proliferation and monocyte chemotactic protein-1 production.
Stable decreases in miR-124 expression contribute to an epigenetically reprogrammed, highly proliferative, migratory, and inflammatory phenotype of hypertensive pulmonary adventitial fibroblasts. Thus, therapies directed at restoring miR-124 function, including histone deacetylase inhibitors, should be investigated.
anoxia; hypertension; pulmonary; migration; neoplasms; proliferation
Some protein pharmaceuticals from Chinese medicine have been developed to treat cardiovascular diseases, genetic diseases, and cancer. Bioactive proteins with various pharmacological properties have been successfully isolated from animals such as Hirudo medicinalis (medicinal leech), Eisenia fetida (earthworm), and Mesobuthus martensii (Chinese scorpion), and from herbal medicines derived from species such as Cordyceps militaris, Ganoderma, Momordica cochinchinensis, Viscum album, Poria cocos, Senna obtusifolia, Panax notoginseng, Smilax glabra, Ginkgo biloba, Dioscorea batatas, and Trichosanthes kirilowii. This article reviews the isolation methods, molecular characteristics, bioactivities, pharmacological properties, and potential uses of bioactive proteins originating from these Chinese medicines.
Our previous studies have demonstrated the treatment benefits of dense cranial electroacupuncture stimulation (DCEAS), a novel brain stimulation therapy in patients with major depression, postpartum depression and obsessive-compulsive disorder. The purpose of the present study was to further evaluate the effectiveness of DCEAS combined with body acupuncture and selective serotonin reuptake inhibitors (SSRIs) in patients with post-stroke depression (PSD).
In a single-blind, randomized controlled trial, 43 patients with PSD were randomly assigned to 12 sessions of DCEAS plus SSRI plus body electroacupuncture (n = 23), or sham (non-invasive cranial electroacupuncture, n-CEA) plus SSRI plus body electroacupuncture (n = 20) for 3 sessions per week over 4 weeks. Treatment outcomes were measured using the 17-item Hamilton Depression Rating Scale (HAMD-17), the Clinical Global Impression - Severity scale (CGI-S) and Barthel Index (BI), a measure used to evaluate movement ability associated with daily self-caring activity.
DCEAS produced a significantly greater reduction of both HAMD-17 and CGI-S as early as week 1 and CGI-S at endpoint compared to n-CEA, but subjects of n-CEA group exhibited a significantly greater improvement on BI at week 4 than DCEAS. Incidence of adverse events was not different in the two groups.
These results indicate that DCEAS could be effective in reducing stroke patients’ depressive symptoms. Superficial electrical stimulation in n-CEA group may be beneficial in improving movement disability of stroke patients. A combination of DCEAS and body acupuncture can be considered a treatment option for neuropsychiatric sequelae of stroke.
Acupuncture; Post-stroke depression; Rehabilitation; Dense cranial electroacupuncture stimulation; DCEAS; Clinical trial
Translational selection is a ubiquitous and significant mechanism to regulate protein expression in prokaryotes and unicellular eukaryotes. Recent evidence has shown that translational selection is weakly operative in highly expressed genes in human and other vertebrates. However, it remains unclear whether translational selection acts differentially on human genes depending on their expression patterns.
Here we report that human housekeeping (HK) genes that are strictly defined as genes that are expressed ubiquitously and consistently in most or all tissues, are under stronger translational selection.
These observations clearly show that translational selection is also closely associated with expression pattern. Our results suggest that human HK genes are more efficiently and/or accurately translated into proteins, which will inevitably open up a new understanding of HK genes and the regulation of gene expression.
This article was reviewed by Yuan Yuan, Baylor College of Medicine; Han Liang, University of Texas MD Anderson Cancer Center (nominated by Dr Laura Landweber) Eugene Koonin, NCBI, NLM, NIH, United States of America Sandor Pongor, International Centre for Genetic Engineering and biotechnology (ICGEB), Italy.
Translational selection; Codon usage bias; Expression regulation; Housekeeping gene; Tissue-specific gene
Exploring molecular mechanisms underlying bacterial water-to-land transition represents a critical start toward a better understanding of the functioning and stability of the terrestrial ecosystems. Here, we perform comprehensive analyses based on a large variety of bacteria by integrating taxonomic, phylogenetic and metagenomic data, in the quest for a unified view that elucidates genomic, evolutionary and ecological dynamics of the marine progenitors in adapting to nonaquatic environments. We hypothesize that bacterial land colonization is dominated by a single-gene sweep, that is, the emergence of dnaE2 derived from an early duplication event of the primordial dnaE, followed by a series of niche-specific genomic adaptations, including GC content increase, intensive horizontal gene transfer and constant genome expansion. In addition, early bacterial radiation may be stimulated by an explosion of land-borne hosts (for example, plants and animals) after initial land colonization events.
adaptive mutagenesis; bacterial land colonization; GC content; genome expansion; HGT; metagenomics
Dysregulation of glycoproteins is closely related with many diseases. Quantitative proteomics methods are powerful tools for the detection of glycoprotein alterations. However, in almost all quantitative glycoproteomics studies, trypsin is used as the only protease to digest proteins. This conventional method is unable to quantify N-glycosites in very short or long tryptic peptides and so comprehensive glycoproteomics analysis cannot be achieved.
In this study, a comprehensive analysis of the difference of N-glycoproteome between hepatocellular carcinoma (HCC) and normal human liver tissues was performed by an integrated workflow combining the multiple protease digestion and solid phase based labeling. The quantified N-glycoproteins were analyzed by GoMiner to obtain a comparative view of cellular component, biological process and molecular function.
An integrated workflow was developed which enabled the processes of glycoprotein coupling, protease digestion and stable isotope labeling to be performed in one reaction vessel. This workflow was firstly evaluated by analyzing two aliquots of the same protein extract from normal human liver tissue. It was demonstrated that the multiple protease digestion improved the glycoproteome coverage and the quantification accuracy. This workflow was further applied to the differential analysis of N-glycoproteome of normal human liver tissue and that with hepatocellular carcinoma. A total of 2,329 N-glycosites on 1,052 N-glycoproteins were quantified. Among them, 858 N-glycosites were quantified from more than one digestion strategy with over 99% confidence and 1,104 N-glycosites were quantified from only one digestion strategy with over 95% confidence. By comparing the GoMiner results of the N-glycoproteins with and without significant changes, the percentage of membrane and secreted proteins and their featured biological processes were found to be significant different revealing that protein glycosylation may play the vital role in the development of HCC.
N-glycoproteome; N-glycosite; Multiple protease digestion; Quantitative analysis
Retinal post-mitotic neurocytes display genomic instability after damage induced by physiological or pathological factors. The involvement of BRCA1, an important factor in development and DNA repair in mature retinal neurocytes remains unclear. Thus, we investigated the developmental expression profile of BRCA1 in the retina and defined the role of BRCA1 in DNA repair in retinal neurocytes. Our data show the expression of BRCA1 is developmentally down-regulated in the retinas of mice after birth. Similarly, BRCA1 is down-regulated after differentiation induced by TSA in retinal precursor cells. An end-joining activity assay and DNA fragmentation analysis indicated that the DNA repair capacity is significantly reduced. Moreover, DNA damage in differentiated cells or cells in which BRCA1 is silenced by siRNA interference is more extensive than that in precursor cells subjected to ionizing radiation. To further investigate non-homologous end joining (NHEJ), the major repair pathway in non-divided neurons, we utilized an NHEJ substrate (pEPI-NHEJ) in which double strand breaks are generated by I-SceI. Our data showed that differentiation and the down-regulation of BRCA1 respectively result in a 2.39-fold and 1.68-fold reduction in the total NHEJ frequency compared with that in cells with normal BRCA1. Furthermore, the analysis of NHEJ repair junctions of the plasmid substrate indicated that BRCA1 is involved in the fidelity of NHEJ. In addition, as expected, the down-regulation of BRCA1 significantly inhibits the viability of retina precursor cells. Therefore, our data suggest that BRCA1 plays a critical role in retinal development and repairs DNA damage of mature retina neurocytes.
Herbal medicine (HM) as an adjunct therapy has been shown to be promising for the chronic obstructive pulmonary disease (COPD). However, the role of herbs in COPD remains largely unexplored. In this present study, we conducted the systematic review to evaluate the efficacy of herbs in COPD. 176 clinical studies with reporting pulmonary function were retrieved from English and Chinese database. Commonly used herbs for acute exacerbations stage (AECOPD) and stable COPD stage (SCOPD) were identified. A meta-analysis conducted from 15 high quality studies (18 publications) showed that HM as an adjunct therapy had no significant improvement in pulmonary function (FEV1, FEV%, FVC, and FEV1/FVC) compared to conventional medicine. The efficacy of the adjunct HM on improving the arterial blood gas (PaCO2 and PaO2) for AECOPD and SCOPD remains inconclusive due to the heterogeneity among the studies. However, HM as an adjunct therapy improved clinical symptoms and quality of life (total score, activity score, and impact score of St. George's Respiratory Questionnaire). Studies with large-scale and double-blind randomized controlled trials are required to confirm the role of the adjunct HM in the management of COPD.
Fractional flow reserve (FFR) is an important prognostic determinant in a clinical setting. However, its measurement currently requires the use of invasive pressure wire, while an angiographic technique based on first-pass distribution analysis and scaling laws can be used to measure FFR using only image data.
Eight anesthetized swine were instrumented with flow probe on the proximal segment of the left anterior descending (LAD) coronary arteries. Volumetric blood flow from the flow probe (Qp), coronary pressure (Pa) and right atrium pressure (Pv) were continuously recorded. Flow probe-based FFR (FFRq) was measured from the ratio of flow with and without stenosis. To determine the angiography-based FFR (FFRa), the ratio of blood flow in the presence of a stenosis (QS) to theoretically normal blood flow (QN) was calculated. A region of interest in the LAD arterial bed was drawn to generate time-density curves using angiographic images. QS was measured using a time-density curve and the assumption that blood was momentarily replaced with contrast agent during the injection. QN was estimated from the total coronary arterial volume using scaling laws. Pressure-wire measurements of FFR (FFRp), which was calculated from the ratio of distal coronary pressure (Pd) divided by proximal pressure (Pa), were continuously obtained during the study.
A total of 54 measurements of FFRa, FFRp, and FFRq were taken. FFRa showed a good correlation with FFRq (FFRa =0.97 FFRq +0.06, r2=0.80, p<0.001), although FFRp overestimated the FFRq (FFRp=0.657 FFRq+0.313, r2 =0.710, p<0.0001). Additionally, the Bland-Altman analysis showed a close agreement between FFRa and FFRq.
This angiographic technique to measure FFR can potentially be used to evaluate both anatomical and physiological assessments of a coronary stenosis during routine diagnostic cardiac catheterization that requires no pressure wires.
Coronary blood flow; Fractional flow reserve; Coronary angiography; Catheterization
Purpose. To determine whether change of apparent diffusion coefficient (ADC) value could predict early response to chemotherapy in lung cancer. Materials and Methods. Twenty-five patients with advanced non-small cell lung cancer underwent chest MR imaging including DWI before and at the end of the first cycle of chemotherapy. The tumor's mean ADC value and diameters on MR images were calculated and compared. The grouping reference was based on serial CT scans according to Response Evaluation Criteria in Solid Tumors. Logistic regression was applied to assess treatment response prediction ability of ADC value and diameters. Results. The change of ADC value in partial response group was higher than that in stable disease group (P = 0.004). ROC curve showed that ADC value could predict treatment response with 100% sensitivity, 64.71% specificity, 57.14% positive predictive value, 100% negative predictive value, and 82.7% accuracy. The area under the curve for combination of ADC value and longest diameter change was higher than any parameter alone (P ≤ 0.01). Conclusions. The change of ADC value may be a sensitive indicator to predict early response to chemotherapy in lung cancer. Prediction ability could be improved by combining the change of ADC value and longest diameter.
Summary: Pan-genome analyses have shed light on the dynamics and evolution of bacterial genome from the point of population. The explosive growth of bacterial genome sequence also brought an extremely big challenge to pan-genome profile analysis. We developed a tool, named PanGP, to complete pan-genome profile analysis for large-scale strains efficiently. PanGP has integrated two sampling algorithms, totally random (TR) and distance guide (DG). The DG algorithm drew sample strain combinations on the basis of genome diversity of bacterial population. The performance of these two algorithms have been evaluated on four bacteria populations with strain numbers varying from 30 to 200, and the DG algorithm exhibited overwhelming advantage on accuracy and stability than the TR algorithm.
Availability: PanGP was developed with a user-friendly graphic interface and it was available at http://PanGP.big.ac.cn.
firstname.lastname@example.org or email@example.com
Supplementary data are available at Bioinformatics online.
Lung cancer is the leading cause of death in cancer patients. Clinical studies showed that a variety of acupoint stimulations have been extensively used for lung cancer patients, including needle insertion, injection with herbal extraction, plaster application, and moxibustion. However, the role of acupoint stimulation in lung cancer treatment was not fully reviewed.
In the present study, we conducted a systematic review and meta-analysis on the role of acupoint stimulation in lung cancer treatment by electronic and manual searching in seven databases, including Ovid (Ovid MEDLINE, AMED, CAB Abstracts, EMBASE), EBSCOhost research databases (Academic Search premier, MEDLINE, CIHAHL Plus), PreQuest (British Nursing Index, ProQuest Medical Library, ProQuest Dissertations & Theses A&I, PsycINFO), and ISI web of knowledge (Web of Science, BIOSIS Citation Index, Biological Abstracts, Chinese Science Citation Database), CNKI, Wanfang Data, and CQVIP.
Our study showed that acupoint stimulation has strong immunomodulatory effect for lung cancer patients as demonstrated by the significant increase of IL-2, T cell subtypes (CD3+ and CD4+, but not CD8+ cells), and natural killer cells. Further analysis revealed that acupoint stimulation remarkably alleviates the conventional therapy-induced bone marrow suppression (hemoglobin, platelet, and WBC reduction) in lung cancer patients, as well as decreases nausea and vomiting. The pooled studies also showed that acupoint stimulation can improve Karnofsky performance status, immediate tumor response, quality of life (EORCT-QLQ-C30), and pain control of cancer patients.
Acupoint stimulation is found to be effective in lung cancer treatment, further confirmatory evaluation via large scale randomized trials is warranted.
Acupuncture; Chinese medicine; Lung cancer; Systematic review; Meta-analysis
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.
Rice is the most important staple food for a large part of the world’s human population and also a key model organism for biological studies of crops as well as other related plants. Here we present RiceWiki (http://ricewiki.big.ac.cn), a wiki-based, publicly editable and open-content platform for community curation of rice genes. Most existing related biological databases are based on expert curation; with the exponentially exploding volume of rice knowledge and other relevant data, however, expert curation becomes increasingly laborious and time-consuming to keep knowledge up-to-date, accurate and comprehensive, struggling with the flood of data and requiring a large number of people getting involved in rice knowledge curation. Unlike extant relevant databases, RiceWiki features harnessing collective intelligence in community curation of rice genes, quantifying users' contributions in each curated gene and providing explicit authorship for each contributor in any given gene, with the aim to exploit the full potential of the scientific community for rice knowledge curation. Based on community curation, RiceWiki bears the potential to make it possible to build a rice encyclopedia by and for the scientific community that harnesses community intelligence for collaborative knowledge curation, covers all aspects of biological knowledge and keeps evolving with novel knowledge.
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.
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
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.
Long non-coding RNAs (lncRNAs) have been found to perform various functions in a wide variety of important biological processes. To make easier interpretation of lncRNA functionality and conduct deep mining on these transcribed sequences, it is convenient to classify lncRNAs into different groups. Here, we summarize classification methods of lncRNAs according to their four major features, namely, genomic location and context, effect exerted on DNA sequences, mechanism of functioning and their targeting mechanism. In combination with the presently available function annotations, we explore potential relationships between different classification categories, and generalize and compare biological features of different lncRNAs within each category. Finally, we present our view on potential further studies. We believe that the classifications of lncRNAs as indicated above are of fundamental importance for lncRNA studies, helpful for further investigation of specific lncRNAs, for formulation of new hypothesis based on different features of lncRNA and for exploration of the underlying lncRNA functional mechanisms.
long non-coding RNA; lncRNA; lncRNA classification; RNA transcripts
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.