Conserved Expression Patterns Predict microRNA Targets

microRNAs (miRNAs) are major regulators of gene expression and thereby modulate many biological processes. Computational methods have been instrumental in understanding how miRNAs bind to mRNAs to induce their repression but have proven inaccurate. Here we describe a novel method that combines expression data from human and mouse to discover conserved patterns of expression between orthologous miRNAs and mRNA genes. This method allowed us to predict thousands of putative miRNA targets. Using the luciferase reporter assay, we confirmed 4 out of 6 of our predictions. In addition, this method predicted many miRNAs that act as expression enhancers. We show that many miRNA enhancer effects are mediated through the repression of negative transcriptional regulators and that this effect could be as common as the widely reported repression activity of miRNAs. Our findings suggest that the indirect enhancement of gene expression by miRNAs could be an important component of miRNA regulation that has been widely neglected to date

Current strategies for treatment of intervertebral disc degeneration: substitution and regeneration possibilities

Background: Intervertebral disc degeneration has an annual worldwide socioeconomic impact masked as low back pain of over 70 billion euros. This disease has a high prevalence over the working age class, which raises the socioeconomic impact over the years. Acute physical trauma or prolonged intervertebral disc mistreatment triggers a biochemical negative tendency of catabolic-anabolic balance that progress to a chronic degeneration disease. Current biomedical treatments are not only ineffective in the long-run, but can also cause degeneration to spread to adjacent intervertebral discs. Regenerative strategies are desperately needed in the clinics, such as: minimal invasive nucleus pulposus or annulus fibrosus treatments, total disc replacement, and cartilaginous endplates decalcification. Main Body: Herein, it is reviewed the state-of-the-art of intervertebral disc regeneration strategies from the perspective of cells, scaffolds, or constructs, including both popular and unique tissue engineering approaches. The premises for cell type and origin selection or even absence of cells is being explored. Choice of several raw materials and scaffold fabrication methods are evaluated. Extensive studies have been developed for fully regeneration of the annulus fibrosus and nucleus pulposus, together or separately, with a long set of different rationales already reported. Recent works show promising biomaterials and processing methods applied to intervertebral disc substitutive or regenerative strategies. Facing the abundance of studies presented in the literature aiming intervertebral disc regeneration it is interesting to observe how cartilaginous endplates have been extensively neglected, being this a major source of nutrients and water supply for the whole disc. Conclusion: Severalinnovative avenues for tackling intervertebral disc degeneration are being reported â from acellular to cellular approaches, but the cartilaginous endplates regeneration strategies remain unaddressed. Interestingly, patient-specific approaches show great promise in respecting patient anatomy and thus allow quicker translation to the clinics in the near future.The authors would like to acknowledge the support provided by the Portuguese Foundation for Science and Technology (FCT) through the project EPIDisc (UTAP-EXPL/BBBECT/0050/2014), funded in the Framework of the “International Collaboratory for Emerging Technologies, CoLab”, UT Austin|Portugal Program. The FCT distinctions attributed to J. Miguel Oliveira (IF/00423/2012 and IF/01285/ 2015) and J. Silva-Correia (IF/00115/2015) under the Investigator FCT program are also greatly acknowledged.info:eu-repo/semantics/publishedVersio

Incremental Interpretation of Categorial Grammar

The paper describes a parser for Categorial Grammar which provides fully word by word incremental interpretation. The parser does not require fragments of sentences to form constituents, and thereby avoids problems of spurious ambiguity. The paper includes a brief discussion of the relationship between basic Categorial Grammar and other formalisms such as HPSG, Dependency Grammar and the Lambek Calculus. It also includes a discussion of some of the issues which arise when parsing lexicalised grammars, and the possibilities for using statistical techniques for tuning to particular languages. 1 Introduction There is a large body of psycholinguistic evidence which suggests that meaning can be extracted before the end of a sentence, and before the end of phrasal constituents (e.g. Marslen-Wilson 1973, Tanenhaus et al. 1990). There is also recent evidence suggesting that, during speech processing, partial interpretations can be built extremely rapidly, even before words are completed (Sp..

The Guessing Game: A Paradigm for Artificial Grammar Learning

In a guessing game, Ss reconstruct a sequence by guessing each successive element of the sequence from a finite set of alternatives, receiving feedback after each guess. An upper bound on Ss knowledge of the sequence is given by H, the estimated entropy of the numbers of guesses. The method provides a measure of learning independent of material type and distractors, and the resulting data set is very rich. Here, the method is applied to artificial grammar learning; Ss were exposed to strings from a finite state grammar and subsequently distinguished between strings that followed or violated the grammar reliably better than Ss who had not seen the learning strings (but who themselves performed at above chance levels). Ss knowledge of the strings, H, reflected both grammaticality and exposure to learning strings, and was correlated with overall judgement performance. For non-grammatical strings, the strings that Ss knew most about were those they found most difficult to classify correc..