The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson9s and Huntington9s disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB 1 receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB 1 receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB 2 receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients9 need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.

http://www.phytecs.com/wp-content/uploads/2015/02/Pharmacol-Rev-2006-Pacher-389-462.pdf

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

A new algorithm for best subsequence alignments with application to tRNA-rRNA comparisons.

http://link.springer.com/content/pdf/10.1007/978-1-4684-4988-4_7.pdf

Evolution of Ribosomal DNA

The coevolution theory of the genetic code, which postulates that prebiotic synthesis was an inadequate source of all twenty protein amino acids, and therefore some of them had to be derived from the coevolving pathways of amino acid biosynthesis, has been assessed in the light of the discoveries of the past three decades. Its four fundamental tenets regarding the essentiality of amino acid biosynthesis, role of pretran synthesis, biosynthetic imprint on codon allocations and mutability of the encoded amino acids are proven by the new knowledge. Of the factors that guided the evolutionary selection of the universal code, the relative contributions of Amino Acid Biosynthesis: Error Minimization: Stereochemical Interaction are estimated to first approximation as 40,000,000:400:1, which suggests that amino acid biosynthesis represents the dominant factor shaping the code. The utility of the coevolution theory is demonstrated by its opening up experimental expansions of the code and providing a basis for locating the root of life.

/pdf/coevolution-theory-of-the-genetic-code-at-age-thirty-13z0dkzyfv.pdf

Coevolution theory of the genetic code at age thirty.

Next-generation DNA sequencing has revolutionized genomic studies and is driving the implementation of precision diagnostics. The ability of these technologies to disentangle sequence heterogeneity, however, is limited by their relatively high error rates. A Several single molecule barcoding strategies have been propose to reduce the overall error frequency. A Duplex Sequencing additionally exploits the fact that DNA is double-strand, with one strand reciprocally encoding the sequence information of its complement, and can eliminate nearly all sequencing errors by comparing the sequence of individually tagged amplicons derived from one strand of DNA with that of its complementary strand. This method reduces errors to fewer than one per ten million nucleotides sequenced.

/pdf/accuracy-of-next-generation-sequencing-platforms-1pgf83opd4.pdf

Accuracy of Next Generation Sequencing Platforms.

/pdf/the-organic-codes-an-introduction-to-semantic-biology-130wjnug2e.pdf

The Organic Codes: an introduction to semantic biology

A model is proposed for the early evolution of the coding mechanism. A primordial RNA embodies the functions of today's nucleic acids in a single molecule. The molecule is generated by successive rounds of self-priming and -templating. After proximity is assured by enclosure in a cell, the functions can be partitioned among more efficient specialized molecules. The prediction of sequence homologies in later forms prompted a search for matches between t- and r-RNAs. These are described. Their distributions offer clues to their origins. The existance of overlapping homologies indicates an approach to the reconstruction of an ancestral molecule.

tRNA-rRNA sequence homologies: a model for the origin of a common ancestral molecule, and prospects for its reconstruction

Original Article INTRODUCTIONHepatotoxicity is a potential complicationfrom the usage of various illicit drugs, possi-bly consequent to their liver metabolism, butinformation on this is scarce in the medicalliterature. Studies on liver damage due tochronic usage of marijuana are rare.Marijuana usage in the form of cigarettesmade from dried leaves, flowers and stalks offemale Cannabis sativa plants has grownstrongly among young Brazilians over the lastdecade. 1 In the United States, after some de-cline in the prevalence of cannabis usage, arecent upsurge has been detected. It has beenconceded that this has taken place consequentto the relaxation of social disapproval of mari-juana usage, a reduction in the perception ofthe risks related to usage and an increase inthe dissemination of pro-drug media mes-sages. 2 In general, marijuana is the first drugto be used. Subsequently, other drugs withstronger effects may substitute for it, or otherlegal or illicit drugs may start to be taken inassociation with it.

/pdf/possible-hepatotoxicity-of-chronic-marijuana-usage-th8h20knrm.pdf

Possible hepatotoxicity of chronic marijuana usage

1. Comparisons were made of the results of searches within and among different species of organisms for sequence matches between transfer RNAs and ribosomal RNAs. The purpose was to determine whether the matching sequences might result from selection acting on the two RNAs within a common cellular environment. 2. The results indicate that most matches do not reflect such selection. The matches described were more frequent than those found in searches among randomized sequences and the frequency of intraspecific matches was not significantly higher than that of interspecific matches. 3. The matches are thought to identify conserved vestiges of a molecule or molecules ancestral to both classes of RNAs (Bloch, D.P., McArthur, B. and Mirrop, S. (1985). BioSystems, 17: 209-225). The matching sequences are interpreted as homologies.

Romeu Cardoso Guimarães

Papers

The Organic Codes: an introduction to semantic biology

tRNA-rRNA sequence homologies: a model for the origin of a common ancestral molecule, and prospects for its reconstruction

Possible hepatotoxicity of chronic marijuana usage

tRNA-rRNA sequence matches from inter- and intraspecies comparisons suggest common origins for the two RNAs.

A self-referential model for the formation of the genetic code.