Sequencing, Analysis, and Annotation of Expressed Sequence Tags for Camelus dromedarius

Despite its economical, cultural, and biological importance, there has not been a large scale sequencing project to date for Camelus dromedarius. With the goal of sequencing complete DNA of the organism, we first established and sequenced camel EST libraries, generating 70,272 reads. Following trimming, chimera check, repeat masking, cluster and assembly, we obtained 23,602 putative gene sequences, out of which over 4,500 potentially novel or fast evolving gene sequences do not carry any homology to other available genomes. Functional annotation of sequences with similarities in nucleotide and protein databases has been obtained using Gene Ontology classification. Comparison to available full length cDNA sequences and Open Reading Frame (ORF) analysis of camel sequences that exhibit homology to known genes show more than 80% of the contigs with an ORF>300 bp and ~40% hits extending to the start codons of full length cDNAs suggesting successful characterization of camel genes. Similarity analyses are done separately for different organisms including human, mouse, bovine, and rat. Accompanying web portal, CAGBASE (http://camel.kacst.edu.sa/), hosts a relational database containing annotated EST sequences and analysis tools with possibility to add sequences from public domain. We anticipate our results to provide a home base for genomic studies of camel and other comparative studies enabling a starting point for whole genome sequencing of the organism

Sequencing, Analysis, and Annotation of Expressed Sequence Tags for \u3ci\u3eCamelus dromedarius\u3c/i\u3e

Despite its economical, cultural, and biological importance, there has not been a large scale sequencing project to date for Camelus dromedarius. With the goal of sequencing complete DNA of the organism, we first established and sequenced camel EST libraries, generating 70,272 reads. Following trimming, chimera check, repeat masking, cluster and assembly, we obtained 23,602 putative gene sequences, out of which over 4,500 potentially novel or fast evolving gene sequences do not carry any homology to other available genomes. Functional annotation of sequences with similarities in nucleotide and protein databases has been obtained using Gene Ontology classification. Comparison to available full length cDNA sequences and Open Reading Frame (ORF) analysis of camel sequences that exhibit homology to known genes show more than 80% of the contigs with an ORF\u3e300 bp and ~40% hits extending to the start codons of full length cDNAs suggesting successful characterization of camel genes. Similarity analyses are done separately for different organisms including human, mouse, bovine, and rat. Accompanying web portal, CAGBASE (http://camel.kacst.edu.sa/), hosts a relational database containing annotated EST sequences and analysis tools with possibility to add sequences from public domain. We anticipate our results to provide a home base for genomic studies of camel and other comparative studies enabling a starting point for whole genome sequencing of the organism

Multivariate k-nearest neighbour regression for time series data - A novel algorithm for forecasting UK electricity demand

The k-nearest neighbour (k-NN) algorithm is one of the most widely used benchmark algorithms in classification, supported by its simplicity and intuitiveness in finding similar instances in multivariate and large-dimensional feature spaces of arbitrary attribute scales. In contrast, only few scientific studies of k-NN exist in forecasting time series data, which have mainly assessed various distance metrics to identify similar univariate time series motifs in past data. In electricity load forecasting, k-NN studies are limited to identifying past motifs of the same dependent variable to match future realisations, in a non-causal approach to forecasting. However, causal information in the form of deterministic calendar information is readily available on past and future time series motifs, allowing the distinction between load profiles of working days, weekends and bank-holidays to be encoded as binary dummy variables, and to be efficiently included in the search for similar neighbours. In this paper, we propose a multivariate k-NN regression method for forecasting the electricity demand in the UK market which utilises binary dummy variables as a second feature to categorise the day being forecasted as a working day or a non-working day. We assess the efficacy of this approach in a robust empirical evaluation using UK electricity load data. The approach shows improvements beyond conventional k-NN approaches and accuracy beyond that of simple statistical benchmark methods

Proangiogenic Effect of Metformin in Endothelial Cells Is via Upregulation of VEGFR1/2 and Their Signaling under Hyperglycemia-Hypoxia

Cardiovascular disease is the leading cause of morbidity/mortality worldwide. Metformin is the first therapy offering cardioprotection in type 2 diabetes and non-diabetic animals with unknown mechanism. We have shown that metformin improves angiogenesis via affecting expression of growth factors/angiogenic inhibitors in CD34+ cells under hyperglycemia-hypoxia. Now we studied the direct effect of physiological dose of metformin on human umbilical vein endothelial cells (HUVEC) under conditions mimicking hypoxia-hyperglycemia. HUVEC migration and apoptosis were studied after induction with euglycemia or hyperglycemia and/or CoCl2 induced hypoxia in the presence or absence of metformin. HUVEC mRNA was assayed by whole transcript microarrays. Genes were confirmed by qRT-PCR, proteins by western blot, ELISA or flow cytometry. Metformin promoted HUVEC migration and inhibited apoptosis via upregulation of vascular endothelial growth factor (VEGF) receptors (VEGFR1/R2), fatty acid binding protein 4 (FABP4), ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte antigen 96, Rho kinase 1 (ROCK1), matrix metalloproteinase 16 (MMP16) and tissue factor inhibitor-2 under hyperglycemia-chemical hypoxia. Therefore, metformin’s dual effect in hyperglycemia-chemical hypoxia is mediated by direct effect on VEGFR1/R2 leading to activation of cell migration through MMP16 and ROCK1 upregulation, and inhibition of apoptosis by increase in phospho-ERK1/2 and FABP4, components of VEGF signaling cascades

Sequencing, Analysis, and Annotation of Expressed Sequence Tags for \u3ci\u3eCamelus dromedarius\u3c/i\u3e

Despite its economical, cultural, and biological importance, there has not been a large scale sequencing project to date for Camelus dromedarius. With the goal of sequencing complete DNA of the organism, we first established and sequenced camel EST libraries, generating 70,272 reads. Following trimming, chimera check, repeat masking, cluster and assembly, we obtained 23,602 putative gene sequences, out of which over 4,500 potentially novel or fast evolving gene sequences do not carry any homology to other available genomes. Functional annotation of sequences with similarities in nucleotide and protein databases has been obtained using Gene Ontology classification. Comparison to available full length cDNA sequences and Open Reading Frame (ORF) analysis of camel sequences that exhibit homology to known genes show more than 80% of the contigs with an ORF\u3e300 bp and ~40% hits extending to the start codons of full length cDNAs suggesting successful characterization of camel genes. Similarity analyses are done separately for different organisms including human, mouse, bovine, and rat. Accompanying web portal, CAGBASE (http://camel.kacst.edu.sa/), hosts a relational database containing annotated EST sequences and analysis tools with possibility to add sequences from public domain. We anticipate our results to provide a home base for genomic studies of camel and other comparative studies enabling a starting point for whole genome sequencing of the organism

Self-Nanoemulsifying Drug Delivery System of 2-Methoxyestradiol Exhibits Enhanced Anti-Proliferative and Pro-Apoptotic Activities in MCF-7 Breast Cancer Cells

(1) Background: 2-Methoxyestradiol (2ME) is a metabolite of estrogens and possesses promising anti-proliferative and cytotoxic activities. However, it suffers unfavorable pharmacokinetic characteristics such as absorption after oral administration. The aim of this study was to prepare an optimized 2ME self-nanoemulsifying drug delivery system (2ME-SNEDDS) and evaluate its cytotoxicity and pro-apoptotic activities in MCF-7 breast cancer cells. (2) Methods: For optimization of the 2ME-SNEDDS, a three-component system was used in the D-optimal mixture experimental study. MCF-7 cells were incubated with the 2ME-SNEDDS and subjected to an assessment of growth inhibition, cell cycle progression, annexin V staining, caspase-3 concentration, Bax, Bcl-2, and cyclin D1 mRNA expression, and reactive oxygen species (ROS) generation. (3) Results: The optimized formula had a globule size of 94.97 ± 4.35 nm. Zeta potential was found to be −3.4 ± 1.2 mV with a polydispersity index (PDI) of 0.34. In addition, 96.3  ± 4.3% of 2ME was released from the 2ME-SNEDDS within 24 h using the activated analysis bag technique. Moreover, the prepared 2ME-SNEDDS exhibited a significant enhancement of the anti-proliferative activity against MCF-7 cells in comparison to raw 2ME. This was associated with cyclin D1 expression down-regulation and the accumulation of cells in the G0/G1 and G2/M phases. The pro-apoptotic activities of the 2ME-SNEDDS were confirmed by annexin V staining, which indicated enhanced early and late cell death. This accompanied modulation of the mRNA expression of Bax and Bcl-2 in favor of apoptosis. The 2ME-SNEDDS significantly enhanced cleaved caspase-3 concentration in comparison to raw 2ME. In addition, the 2ME-SNEDDS significantly increased the generation of ROS in MCF-7 cells. (4) Conclusions: The 2ME-SNEDDS exhibits enhanced cytotoxicity and pro-apoptotic activity in MCF-7 cells. This is mediated by, at least partially, ROS generation

Correction: Al-Qahtani et al. Self-Nanoemulsifying Drug Delivery System of 2-Methoxyestradiol Exhibits Enhanced Anti-Proliferative and Pro-Apoptotic Activities in MCF-7 Breast Cancer Cells. <i>Life</i> 2022, <i>12,</i> 1369

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