RNA-Seq analysis and comparison of corneal epithelium in keratoconus and myopia patients

© 2017 The Author(s). Keratoconus is a common degenerative corneal disease that can lead to significant visual morbidity, and both genetic and environmental factors have been implicated in its pathogenesis. We compared the transcriptome of keratoconus and control epithelium using RNA-Seq. Epithelial tissues were obtained prior to surgery from keratoconus and myopia control patients, undergoing collagen cross-linking and photorefractive keratectomy, respectively. We identified major differences in keratoconus linked to cell-cell communication, cell signalling and cellular metabolism. The genes associated with the Hedgehog, Wnt and Notch1 signaling pathways were down-regulated in keratoconus. We also identified plasmolipin and Notch1 as being significantly reduced in keratoconus for both gene and protein expression (p < 0.05). Plasmolipin is a novel protein identified in human corneal epithelium, and has been demonstrated to have a key role in epithelial cell differentiation in other tissues. This study shows altered gene and protein expression of these three proteins in keratoconus, and further studies are clearly warranted to confirm the functional role of these proteins in the pathogenesis of keratoconus

Author Correction: RNA-Seq analysis and comparison of corneal epithelium in keratoconus and myopia patients.

In the original version of this Article, a relevant paper on the detection of PLLP in human corneal epithelium during KC pathogenesis was not cited. This article is now cited as Ref 56 and discussed. As a result, in the Conclusion, "Notch1 and PLLP have not previously been linked to KC pathogenesis. PLLP has not been previously reported to be expressed in human corneal epithelium, although its roles in other tissues suggests it could play a critical role in normal corneal epithelial cellular activities, and interact with the Notch1 signaling pathway." now reads: "Notch1 has not previously been linked to KC pathogenesis. PLLP was reported to be upregulated in KC corneal epithelium compared to normal through proteomic analysis56. Both previous finding and our paper suggested an abnormal expression of PLLP in KC, however our study showed PLLP was down-regulated in KC. The difference can be attributed to the sample types and preparation. Myopia rather than normal corneal samples were used as control in this study. We measured and compared PLLP expression in each sample, whereas the previous study used pooled sample56 and therefore may mask the individual differences. The role of PLLP in human corneal epithelium is unclear, however findings from studies in other tissues suggest that it could be important in maintaining normal corneal epithelial cellular activities and interact with the Notch 1 signalling pathway." Subsequent references in the Article have been renumbered accordingly. The original Article has been corrected

Are uranium-contaminated soil and irrigation water a risk for human vegetable consumers? A study case with Solanum tuberosum L., Phaseolus vulgaris L. and Lactuca sativa L.

The knowledge of uranium concentration, in the products entering the human diet is of extreme importance because of their chemical hazard to health. Controlled field experiments with potatoes, beans and lettuce (Solanum tuberosum L., Phaseolus vulgaris L. and Lactuca sativa L.) were carried out in a contaminated soil used by local farmers located near a closed Portuguese uranium mine (Cunha Baixa, Mangualde). The soil with high average uranium levels (64–252 mg/kg) was divided in two plots, and irrigated with non-contaminated and uranium-contaminated water (\20 and [900 lg/L). Uranium maximum average concentration in the edible vegetables parts (mg/kg fresh weight) ranged in the following order: lettuce (234 lg/kg)[green bean (30 lg/kg)[potatoes without peel (4 lg/kg). Although uranium in soil, irrigation water and vegetables was high, the assessment of the health risk based on hazard quotient indicates that consumption of these vegetables does not represent potential adverse (no carcinogenic) effects for a local inhabitant during lifetime

The Classic: Bone Morphogenetic Protein

This Classic Article is a reprint of the original work by Marshall R. Urist and Basil S. Strates, Bone Morphogenetic Protein. An accompanying biographical sketch of Marshall R. Urist, MD is available at DOI 10.1007/s11999-009-1067-4; a second Classic Article is available at DOI 10.1007/s11999-009-1069-2; and a third Classic Article is available at DOI 10.1007/s11999-009-1070-9. The Classic Article is © 1971 by Sage Publications Inc. Journals and is reprinted with permission from Urist MR, Strates BS. Bone morphogenetic protein. J Dent Res. 1971;50:1392–1406

Outlier Edge Detection Using Random Graph Generation Models and Applications

Outliers are samples that are generated by different mechanisms from other normal data samples. Graphs, in particular social network graphs, may contain nodes and edges that are made by scammers, malicious programs or mistakenly by normal users. Detecting outlier nodes and edges is important for data mining and graph analytics. However, previous research in the field has merely focused on detecting outlier nodes. In this article, we study the properties of edges and propose outlier edge detection algorithms using two random graph generation models. We found that the edge-ego-network, which can be defined as the induced graph that contains two end nodes of an edge, their neighboring nodes and the edges that link these nodes, contains critical information to detect outlier edges. We evaluated the proposed algorithms by injecting outlier edges into some real-world graph data. Experiment results show that the proposed algorithms can effectively detect outlier edges. In particular, the algorithm based on the Preferential Attachment Random Graph Generation model consistently gives good performance regardless of the test graph data. Further more, the proposed algorithms are not limited in the area of outlier edge detection. We demonstrate three different applications that benefit from the proposed algorithms: 1) a preprocessing tool that improves the performance of graph clustering algorithms; 2) an outlier node detection algorithm; and 3) a novel noisy data clustering algorithm. These applications show the great potential of the proposed outlier edge detection techniques.Comment: 14 pages, 5 figures, journal pape

The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo

The CACCC-box binding protein erythroid Kruppel-like factor (EKLF/KLF1) is a master regulator that directs the expression of many important erythroid genes. We have previously shown that EKLF drives transcription of the gene for a second KLF, basic Kruppel-like factor, or KLF3. We have now tested the in vivo role of KLF3 in erythroid cells by examining Klf3 knockout mice. KLF3-deficient adults exhibit a mild compensated anemia, including enlarged spleens, increased red pulp, and a higher percentage of erythroid progenitors, together with elevated reticulocytes and abnormal erythrocytes in the peripheral blood. Impaired erythroid maturation is also observed in the fetal liver. We have found that KLF3 levels rise as erythroid cells mature to become TER119(+). Consistent with this, microarray analysis of both TER119(-) and TER119(+) erythroid populations revealed that KLF3 is most critical at the later stages of erythroid maturation and is indeed primarily a transcriptional repressor. Notably, many of the genes repressed by KLF3 are also known to be activated by EKLF. However, the majority of these are not currently recognized as erythroid-cell-specific genes. These results reveal the molecular and physiological function of KLF3, defining it as a feedback repressor that counters the activity of EKLF at selected target genes to achieve normal erythropoiesis

Integrating personality research and animal contest theory: aggressiveness in the green swordtail <i>Xiphophorus helleri</i>

&lt;p&gt;Aggression occurs when individuals compete over limiting resources. While theoretical studies have long placed a strong emphasis on context-specificity of aggression, there is increasing recognition that consistent behavioural differences exist among individuals, and that aggressiveness may be an important component of individual personality. Though empirical studies tend to focus on one aspect or the other, we suggest there is merit in modelling both within-and among-individual variation in agonistic behaviour simultaneously. Here, we demonstrate how this can be achieved using multivariate linear mixed effect models. Using data from repeated mirror trials and dyadic interactions of male green swordtails, &lt;i&gt;Xiphophorus helleri&lt;/i&gt;, we show repeatable components of (co)variation in a suite of agonistic behaviour that is broadly consistent with a major axis of variation in aggressiveness. We also show that observed focal behaviour is dependent on opponent effects, which can themselves be repeatable but were more generally found to be context specific. In particular, our models show that within-individual variation in agonistic behaviour is explained, at least in part, by the relative size of a live opponent as predicted by contest theory. Finally, we suggest several additional applications of the multivariate models demonstrated here. These include testing the recently queried functional equivalence of alternative experimental approaches, (e. g., mirror trials, dyadic interaction tests) for assaying individual aggressiveness.&lt;/p&gt

Star forming dwarf galaxies

Star forming dwarf galaxies (SFDGs) have a high gas content and low metallicities, reminiscent of the basic entities in hierarchical galaxy formation scenarios. In the young universe they probably also played a major role in the cosmic reionization. Their abundant presence in the local volume and their youthful character make them ideal objects for detailed studies of the initial stellar mass function (IMF), fundamental star formation processes and its feedback to the interstellar medium. Occasionally we witness SFDGs involved in extreme starbursts, giving rise to strongly elevated production of super star clusters and global superwinds, mechanisms yet to be explored in more detail. SFDGs is the initial state of all dwarf galaxies and the relation to the environment provides us with a key to how different types of dwarf galaxies are emerging. In this review we will put the emphasis on the exotic starburst phase, as it seems less important for present day galaxy evolution but perhaps fundamental in the initial phase of galaxy formation.Comment: To appear in JENAM Symposium "Dwarf Galaxies: Keys to Galaxy Formation and Evolution", P. Papaderos, G. Hensler, S. Recchi (eds.). Lisbon, September 2010, Springer Verlag, in pres

Interleukin-6 gene amplification and shortened survival in glioblastoma patients

Interleukin-6 (IL-6) is known to promote tumour growth and survival. We evaluated IL-6 gene amplification in tumours from 53 glioma patients using fluorescence in situ hybridisation. Amplification events were detected only in glioblastomas (15 out of 36 cases), the most malignant tumours, and were significantly associated with decreased patient survival

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function