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A subset of co-expressed genes in Slug-based cancer mesenchymal transition signature remains coexpressed in normal samples in a tissue-specific manner
Full text linkA recently identified gene expression signature of EMT markers containing the transcription factor Slug was found present in samples from many publicly available cancer gene expression datasets of multiple cancer types except leukemia. We also found many of these genes co-expressed in human cancer xenografted cells, but not in mouse stroma cells, suggesting that the signature is largely produced by cancer cells undergoing some type of EMT. Here we report that a partial signature consisting of a subset of the co-expressed genes of the full signature, including at least Slug (SNAI2), collagens COL1A1, COL1A2, COL3A1, COL6A3 and genes DCN and LUM, is also present in leukemia, in which case it is also strongly associated with the chemokine CXCL12 (aka SDF1). The same subset of co-expressed genes is also strongly present even in normal samples in a tissue-specific manner, with lowest expression in brain tissues and highest expression in reproductive system tissues. The full signature, with prominent presence of COL11A1, THBS2 and INHBA appears to be triggered in solid cancers particularly when cancer cells encounter adipocytes
A Database for TSSs of Human MicroRNAs
Full text linkMicroRNAs (miRNAs) are small endogeneous non-coding RNAs of about 22nt length. These short RNAs regulate the expression of mRNAs by hybridizing with their 3'-UTRs or by translational repression. They have been shown to take crucial roles in many biological processes. Many of the current studies are focused over how mature miRNAs regulate mRNAs, even though there is very limited knowledge about their transcriptional loci. Primary miRNAs (pri-miRs) are first transcribed from the DNA, followed by the formation of precursor miRNA (pre-miR) by endonucleases activity, which finally produces mature miRNAs. Unfortunately, the identification of the loci of pri-miRs, and the associated information about transcription start sites (TSSs) and promoters is still in progress. This information, even though limited, may be useful for further study on the regulation of miRNAs. In this paper, we provide a novel database of miRNA TSSs (miRT) that might be a valuable resource for advanced research on miRNA regulation
Beyond the fuzzy lock-and-key: spontaneous symmetry shifts and glycan/lectin logic gates
Full text linkChanges in the molecular topology of glycan/lectin interaction may explain observed reaction punctuation driven by experimental gradients in reactant concentration. Adoption of a 'biological renormalization' perspective from statistical physics for the analysis of such phase transitions suggests, in marked contrast to conventional physical systems, a broad spectrum of possible universality class behaviors. This spectrum may, in typical perverse biological manner, be of central scientific interest. Generalization, via formalism abducted from coevolutionary theory, suggests that glycan/lectin molecular switches instantiate logic gates that may be as sophisticated as those characterizing basic neural process, if on a different scale
Gender effects on cytidine analogue metabolism and myelodysplastic syndrome treatment outcomes
Full text linkIn vivo, half-lives of cytidine analogues such as 5-azacytidine and decitabine, used to treat myelodysplastic syndromes (MDS), are determined largely by cytidine deaminase (CDA), an enzyme that rapidly metabolizes these drugs into inactive uridine counterparts. Genetic factors influence CDA activity, and hence, could impact 5-azacytidine/decitabine levels and efficacy, a possibility requiring evaluation. Using an HPLC assay, plasma CDA activity was confirmed to be decreased in individuals with the CDA SNP A79C. More interestingly, there was an even larger decrease in females. Explaining the decrease in enzyme activity, liver CDA expression was significantly lower in female versus male mice. As expected, decitabine plasma levels, measured by mass-spectrometry, were significantly higher in females. In mathematical modeling, the detrimental effect of shortening half-life of S-phase specific therapy was amplified in low S-phase fraction disease (e.g., MDS). Accordingly, in multivariate analysis of MDS patients treated with 5-azacytidine/decitabine, overall survival was significantly worse in males
The phage-host interaction as a model for studying carbon regulation in aquatic system
Full text linkThis document contains the presentation by Swapnil G Sanmukh et al, National Environmental Engineering Research Institute (NEERI), Nagpur on “The phage-host interaction as a model for studying carbon regulation in aquatic system” during Second National Research Conference on Climate Change, organized by the Centre for Science and Environment, IIT Delhi and IIT Madras on November 5-6, 2011 at New Delhi
Nonlinear Models of Neural and Genetic Network Dynamics
Full text linkA categorical and Łukasiewicz-Topos framework for Łukasiewicz LM-Algebraic Logic models of nonlinear dynamics in complex functional systems such as neural networks, genomes and cell interactomes is proposed. Łukasiewicz Algebraic Logic models of genetic networks and signaling pathways in cells are formulated in terms of nonlinear dynamic systems with n-state components that allow for the generalization of previous logical models of both genetic activities and neural networks
Inhaled Insulin: Intrapulmonary or Intranasal?
Full text linkInitial attempts delivered the insulin hormone intramuscularly, intravenously, and eventually subcutaneously. Other routes of administration of the drug were explored. These included oral, rectal, sublingual, buccal, transdermal, vaginal, intramuscular, intrapulmonary, and intranasal delivery systems. The purpose of these latter studies was to determine a noninjectable method to deliver insulin to patients with type 1 and 2 diabetes that would effectively lower blood sugar, control hemoglobin A1c (in much later studies), and allow patients a simpler, less invasive, and more direct control oftheir underlying disease process.  In January 2006 the United States Food and Drug Administration approved Exubera (Pfizer Pharmaceuticals, New York, NY) as the first pulmonary inhaled insulin. In actuality attempts to explore various methods to deliver insulin using intrapulmonary delivery had occurred since1925. 
On Asymmetry in Biology and Nature
Full text linkSymmetry has attracted a substantial amount of effort because considerable simplifications are possible in the mathematical and physical treatment of phenomena and natural systems that possess a certain degree of symmetry. Among physical and chemical systems the most widely known are those related to crystals and fluids. Whereas crystals have a lattice structure and a symmetry caused by ‘perfect’ order which can be classified by mathematical symmetry groups, most fluids have an average isotropic, highly-disordered ‘structure’ that is often considered to be random.Asymmetry is widely encountered in Biology and ecological systems- from amino acids to trees forests, and tribes, from physiological processes to anatomy- one often finds asymmetry to be present , although symmetries are also encountered whenever nature affords it. An important case is that of cell biomembranes that possess a marked structural and functional asymmetry which is essential to the survival of cells and microorganisms. Asymmetry both in time and selection ‘criteria’ plays a key role in the evolution of organisms and species
Detecting differential usage of exons from RNA-Seq data
Full text linkRNA-Seq is a powerful tool for the study of alternative splicing and other forms of alternative isoform expression. Understanding the regulation of these processes requires sensitive and specific detection of differential isoform abundance in comparisons between conditions, cell types or tissues. We present DEXSeq, a statistical method to test for differential exon usage in RNA-Seq data. DEXSeq employs generalized linear models and offers reliable control of false discoveries by taking biological variation into account. DEXSeq detects genes, and in many cases specific exons, that are subject to differential exon usage with high sensitivity. We demonstrate the versatility of DEXSeq by applying it to several data sets. The method facilitates the study of regulation and function of alternative exon usage on a genome-wide scale. An implementation of DEXSeq is available as an R/Bioconductor package.

This preprint has subsequently been published in Genome Research (doi:10.1101/gr.133744.111
Crosstalk and the spectrum of biological global broadcasts: Toward generalization of the Baars consciousness model across physiological subsystems
Full text linkOnce cognitive biological phenomena are recognized as necessarily having 'dual' information sources, it is easy to show that the information theory chain rule implies isolating coresident information sources from crosstalk requires more metabolic free energy than permitting correlation. This provides conditions for an evolutionary exaptation leading to dynamic global broadcasts of interacting cognitive biological processes analogous to, but slower than, consciousness, itself included within the paradigm. The argument is closely analogous to the well-studied exaptation of noise to trigger stochastic resonance amplification in physiological systems