Multistable Decision Switches for Flexible Control of Epigenetic Differentiation

It is now recognized that molecular circuits with positive feedback can induce two different gene expression states (bistability) under the very same cellular conditions. Whether, and how, cells make use of the coexistence of a larger number of stable states (multistability) is however largely unknown. Here, we first examine how autoregulation, a common attribute of genetic master regulators, facilitates multistability in two-component circuits. A systematic exploration of these modules' parameter space reveals two classes of molecular switches, involving transitions in bistable (progression switches) or multistable (decision switches) regimes. We demonstrate the potential of decision switches for multifaceted stimulus processing, including strength, duration, and flexible discrimination. These tasks enhance response specificity, help to store short-term memories of recent signaling events, stabilize transient gene expression, and enable stochastic fate commitment. The relevance of these circuits is further supported by biological data, because we find them in numerous developmental scenarios. Indeed, many of the presented information-processing features of decision switches could ultimately demonstrate a more flexible control of epigenetic differentiation

Microsatellite diversity and genetic structure among common bean (Phaseolus vulgaris L.) landraces in Brazil, a secondary center of diversity

Brazil is the largest producer and consumer of common bean (Phaseolus vulgaris L.), which is the most important source of human dietary protein in that country. This study assessed the genetic diversity and the structure of a sample of 279 geo-referenced common bean landraces from Brazil, using molecular markers. Sixty-seven microsatellite markers spread over the 11 linkage groups of the common bean genome, as well as Phaseolin, PvTFL1y, APA and four SCAR markers were used. As expected, the sample showed lower genetic diversity compared to the diversity in the primary center of diversification. Andean and Mesoamerican gene pools were both present but the latter gene pool was four times more frequent than the former. The two gene pools could be clearly distinguished; limited admixture was observed between these groups. The Mesoamerican group consisted of two sub-populations, with a high level of admixture between them leading to a large proportion of stabilized hybrids not observed in the centers of domestication. Thus, Brazil can be considered a secondary center of diversification of common bean. A high degree of genome-wide multilocus associations even among unlinked loci was observed, confirming the high level of structure in the sample and suggesting that association mapping should be conducted in separate Andean and Mesoamerican Brazilian samples

Persistent developmental stuttering as a cortical-subcortical dysfunction: evidence from muscle activation Gagueira persistente do desenvolvimento como disfunção córtico-subcortical: evidências pela ativação muscular

BACKGROUND: One contemporary view of stuttering posits that speech disfluencies arise from anomalous speech motor control. PURPOSE: To verify the rest muscle tension and speech reaction time of fluent and stuttering adults. METHOD: 22 adults, divided in two groups: G1 - 11 fluent individuals; G2 - 11 stutterers. Electromyography recordings (inferior orbicularis oris) were collected in two different situations: during rest and in a reaction time activity. RESULTS: The groups were significantly different considering rest muscle tension (G2 higher recordings) and did not differ when considering speech reaction time and muscle activity during speech. There was a strong positive correlation between speech reaction time and speech muscle activity for G2 - the longer the speech reaction time, the higher the muscle activity during speech. CONCLUSION: In addition to perceptible episodes of speech disfluency, stutterers exhibit anomalies in speech motor output during fluent speech. Correlations with a possible cortical-subcortical disorder are discussed.<br>INTRODUÇÃO: Atualmente considera-se que as disfluências da fala na gagueira sejam decorrentes de controle motor anormal. OBJETIVO: Verificar o repouso e tempo de reação para fala em adultos fluentes e gagos. MÉTODO: 22 adultos, divididos em dois grupos: G1 - 11 fluentes; G2 - 11 gagos. Os dados eletromiográficos (orbicular dos lábios inferior) foram obtidos em duas situações: repouso e atividade de tempo de reação. RESULTADOS: Os grupos apresentaram diferenças significantes para a tensão muscular de repouso (G2 valores maiores) e não se diferenciaram quanto ao tempo de reação e atividade muscular de fala. Houve correlação positiva entre o tempo de reação e a atividade muscular de fala para G2 - quanto maior o tempo de reação maior a atividade muscular de fala. CONCLUSÃO: Além dos episódios perceptíveis de disfluência, gagos apresentam alterações no output motor de fala durante a produção da fala fluente. Correlações com possível distúrbio cortico-subcortical são discutidas