Evolutionary pressures on simple sequence repeats in prokaryotic coding regions

Simple sequence repeats (SSRs) are indel mutational hotspots in genomes. In prokaryotes, SSR loci can cause phase variation, a microbial survival strategy that relies on stochastic, reversible on–off switching of gene activity. By analyzing multiple strains of 42 fully sequenced prokaryotic species, we measure the relative variability and density distribution of SSRs in coding regions. We demonstrate that repeat type strongly influences indel mutation rates, and that the most mutable types are most strongly avoided across genomes. We thoroughly characterize SSR density and variability as a function of N→C position along protein sequences. Using codon-shuffling algorithms that preserve amino acid sequence, we assess evolutionary pressures on SSRs. We find that coding sequences suppress repeats in the middle of proteins, and enrich repeats near termini, yielding U-shaped SSR density curves. We show that for many species this characteristic shape can be attributed to purely biophysical constraints of protein structure. In multiple cases, however, particularly in certain pathogenic bacteria, we observe over enrichment of SSRs near protein N-termini significantly beyond expectation based on structural constraints. This increases the probability that frameshifts result in non-functional proteins, revealing that these species may evolutionarily tune SSR positions in coding regions to facilitate phase variation

The nonmedical use of prescription ADHD medications: results from a national Internet panel

© 2007 Novak et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Homopolymer tract length dependent enrichments in functional regions of 27 eukaryotes and their novel dependence on the organism DNA (G+C)% composition

BACKGROUND: DNA homopolymer tracts, poly(dA).poly(dT) and poly(dG).poly(dC), are the simplest of simple sequence repeats. Homopolymer tracts have been systematically examined in the coding, intron and flanking regions of a limited number of eukaryotes. As the number of DNA sequences publicly available increases, the representation (over and under) of homopolymer tracts of different lengths in these regions of different genomes can be compared. RESULTS: We carried out a survey of the extent of homopolymer tract over-representation (enrichment) and over-proportional length distribution (above expected length) primarily in the single gene documents, but including some whole chromosomes of 27 eukaryotics across the (G+C)% composition range from 20 – 60%. A total of 5.2 × 10(7 )bases from 15,560 cleaned (redundancy removed) sequence documents were analyzed. Calculated frequencies of non-overlapping long homopolymer tracts were found over-represented in non-coding sequences of eukaryotes. Long poly(dA).poly(dT) tracts demonstrated an exponential increase with tract length compared to predicted frequencies. A novel negative slope was observed for all eukaryotes between their (G+C)% composition and the threshold length N where poly(dA).poly(dT) tracts exhibited over-representation and a corresponding positive slope was observed for poly(dG).poly(dC) tracts. Tract size thresholds where over-representation of tracts in different eukaryotes began to occur was between 4 – 11 bp depending upon the organism (G+C)% composition. The higher the GC%, the lower the threshold N value was for poly(dA).poly(dT) tracts, meaning that the over-representation happens at relatively lower tract length in more GC-rich surrounding sequence. We also observed a novel relationship between the highest over-representations, as well as lengths of homopolymer tracts in excess of their random occurrence expected maximum lengths. CONCLUSIONS: We discuss how our novel tract over-representation observations can be accounted for by a few models. A likely model for poly(dA).poly(dT) tract over-representation involves the known insertion into genomes of DNA synthesized from retroviral mRNAs containing 3' polyA tails. A proposed model that can account for a number of our observed results, concerns the origin of the isochore nature of eukaryotic genomes via a non-equilibrium GC% dependent mutation rate mechanism. Our data also suggest that tract lengthening via slip strand replication is not governed by a simple thermodynamic loop energy model

Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics

Sattler S, Mehlkop G, Graeff P, Sauer C. Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics. Substance Abuse Treatment, Prevention, and Policy. 2014;9(1): 8.Background The use of cognitive enhancement (CE) by means of pharmaceutical agents has been the subject of intense debate both among scientists and in the media. This study investigates several drivers of and obstacles to the willingness to use prescription drugs non-medically for augmenting brain capacity. Methods We conducted a web-based study among 2,877 students from randomly selected disciplines at German universities. Using a factorial survey, respondents expressed their willingness to take various hypothetical CE-drugs; the drugs were described by five experimentally varied characteristics and the social environment by three varied characteristics. Personal characteristics and demographic controls were also measured. Results We found that 65.3% of the respondents staunchly refused to use CE-drugs. The results of a multivariate negative binomial regression indicated that respondents’ willingness to use CE-drugs increased if the potential drugs promised a significant augmentation of mental capacity and a high probability of achieving this augmentation. Willingness decreased when there was a high probability of side effects and a high price. Prevalent CE-drug use among peers increased willingness, whereas a social environment that strongly disapproved of these drugs decreased it. Regarding the respondents’ characteristics, pronounced academic procrastination, high cognitive test anxiety, low intrinsic motivation, low internalization of social norms against CE-drug use, and past experiences with CE-drugs increased willingness. The potential severity of side effects, social recommendations about using CE-drugs, risk preferences, and competencies had no measured effects upon willingness. Conclusions These findings contribute to understanding factors that influence the willingness to use CE-drugs. They support the assumption of instrumental drug use and may contribute to the development of prevention, policy, and educational strategies

U potrazi za optimalnom psihoaktivacijom – stimulansi kao pojačivači kognitivne funkcije

An increasing number of people, students in particular, seek substances that improve their cognitive functioning. The most popular group of pharmacological cognitive enhancers (PCEs) are stimulants. Available studies suggest a small beneficial effect of methylphenidate and amphetamine on memory, executive functions, and processing speed. However small, this effect can make the difference between success and failure. In recent years, research has focused on the additional beneficial effect on the emotional state, increased motivation, and placebo-induced cognitive enhancement. This paper briefly reviews the latest and most important research on the relationship between popular stimulants and cognitive enhancement. One cannot understand this relationship without understanding the Yerkes-Dodson law, which explains the relationship between the degree of arousal and performance. It suggests that the effect of stimulants is a dose-dependent continuum. This law has repeatedly been confirmed by studies in which an optimal level of psychoactivation for cognitive enhancement was obtained with low stimulant doses, whereas exceeding the effective dose resulted in cognitive deficits, psychomotor agitation, and addiction. A separate section has been devoted to modafinil, an increasingly popular stimulant that differs from the rest in neurochemical profile and behavioural effects.Sve više ljudi, napose studenata, traži tvari kojima će poboljšati svoju kognitivnu funkciju. Najpopularniji među farmakološkim pojačivačima kognitivne funkcije jesu stimulansi. Rezultati dostupnih istraživanja pokazuju blago, povoljno djelovanje metilfenidata i amfetamina na pamćenje, izvršne funkcije i brzinu obrade (procesiranja). Premda je poboljšanje blago, ono u studenata može značiti razliku između uspjeha i neuspjeha. Posljednjih se je godina istraživanje usmjerilo na dodatne povoljne učinke stimulansa na emocionalno stanje, povećanu motivaciju, pa i na kognitivna poboljšanja povezana s placebom. U ovom se radu daje kratki pregled najnovijih i najvažnijih istraživanja odnosa između popularnih stimulansa i poboljšanja kognitivne funkcije. Taj se odnos ne može razumjeti bez poznavanja Yerkes-Dodsonova zakona, koji objašnjava odnos između razine uzbuđenosti i izvedbe (performanse) te govori o tome da stimulansi djeluju u kontinuumu koji je ovisan o dozi. Zakon je opetovano potvrđivan istraživanjima u kojima je optimalna razina psihoaktivacije za poboljšanje kognitivne funkcije postignuta niskim dozama stimulansa, a previsoke razine dovodile su do pada kognitivnih deficita, psihomotorne agitacije i ovisnosti. Dio je teksta posvećen modafinilu, sve popularnijem stimulansu koji se svojim neurokemijskim svojstvima i djelovanjem na ponašanje razlikuje od ostalih