Melanism in Peromyscus Is Caused by Independent Mutations in Agouti

Identifying the molecular basis of phenotypes that have evolved independently can provide insight into the ways genetic and developmental constraints influence the maintenance of phenotypic diversity. Melanic (darkly pigmented) phenotypes in mammals provide a potent system in which to study the genetic basis of naturally occurring mutant phenotypes because melanism occurs in many mammals, and the mammalian pigmentation pathway is well understood. Spontaneous alleles of a few key pigmentation loci are known to cause melanism in domestic or laboratory populations of mammals, but in natural populations, mutations at one gene, the melanocortin-1 receptor (Mc1r), have been implicated in the vast majority of cases, possibly due to its minimal pleiotropic effects. To investigate whether mutations in this or other genes cause melanism in the wild, we investigated the genetic basis of melanism in the rodent genus Peromyscus, in which melanic mice have been reported in several populations. We focused on two genes known to cause melanism in other taxa, Mc1r and its antagonist, the agouti signaling protein (Agouti). While variation in the Mc1r coding region does not correlate with melanism in any population, in a New Hampshire population, we find that a 125-kb deletion, which includes the upstream regulatory region and exons 1 and 2 of Agouti, results in a loss of Agouti expression and is perfectly associated with melanic color. In a second population from Alaska, we find that a premature stop codon in exon 3 of Agouti is associated with a similar melanic phenotype. These results show that melanism has evolved independently in these populations through mutations in the same gene, and suggest that melanism produced by mutations in genes other than Mc1r may be more common than previously thought

Dynamic Effective Connectivity of Inter-Areal Brain Circuits

Anatomic connections between brain areas affect information flow between neuronal circuits and the synchronization of neuronal activity. However, such structural connectivity does not coincide with effective connectivity (or, more precisely, causal connectivity), related to the elusive question “Which areas cause the present activity of which others?”. Effective connectivity is directed and depends flexibly on contexts and tasks. Here we show that dynamic effective connectivity can emerge from transitions in the collective organization of coherent neural activity. Integrating simulation and semi-analytic approaches, we study mesoscale network motifs of interacting cortical areas, modeled as large random networks of spiking neurons or as simple rate units. Through a causal analysis of time-series of model neural activity, we show that different dynamical states generated by a same structural connectivity motif correspond to distinct effective connectivity motifs. Such effective motifs can display a dominant directionality, due to spontaneous symmetry breaking and effective entrainment between local brain rhythms, although all connections in the considered structural motifs are reciprocal. We show then that transitions between effective connectivity configurations (like, for instance, reversal in the direction of inter-areal interactions) can be triggered reliably by brief perturbation inputs, properly timed with respect to an ongoing local oscillation, without the need for plastic synaptic changes. Finally, we analyze how the information encoded in spiking patterns of a local neuronal population is propagated across a fixed structural connectivity motif, demonstrating that changes in the active effective connectivity regulate both the efficiency and the directionality of information transfer. Previous studies stressed the role played by coherent oscillations in establishing efficient communication between distant areas. Going beyond these early proposals, we advance here that dynamic interactions between brain rhythms provide as well the basis for the self-organized control of this “communication-through-coherence”, making thus possible a fast “on-demand” reconfiguration of global information routing modalities

A multicenter controlled trial on knowledge and attitude about cardiopulmonary resuscitation among secondary school children in Malaysia

BACKGROUND: We performed a multicenter controlled trial to assess the knowledge and attitude (KA) about cardiopulmonary resuscitation (CPR) among secondary school children in a district in Malaysia. METHODS: This was a prospective intervention study. The primary endpoint of the study was to determine the level of KA about resuscitation after CPR training. The six schools and classes from selected schools were chosen by randomization among the form three and four classes using sealed envelopes. A fully validated questionnaire consisting of three sections (sociodemographic, knowledge and attitude) was given to the pupils before and 2 weeks after the intervention. The intervention group was given a lecture, video show, pamphlet and 1-h practical session on CPR training. The control group received a placebo in order to overcome the learning effect. The maximum scores for the knowledge and attitude sections were 72 and 28, respectively. Repeated measures ANOVA analysis was used for specific objectives to determine the changes in knowledge and attitude level pre- and post-intervention for both study groups. P-values less than 0.05 were taken as significant at 95% confidence intervals. RESULTS: The mean (SD) total knowledge scores for the intervention (n = 216) and control (n = 252) groups were 62.43 (13.68) and 62.29 (12.11), respectively (maximum score 72) (p > 0.05). On the other hand, the mean (SD) total attitude scores for the intervention and the control groups were 19.33 (4.51) and 17.85 (4.52), respectively (maximum score 28) (p < 0.001). There were significant differences in mean knowledge and attitude scores between the intervention and control groups with regard to time (pre- and post-intervention). The mean difference in knowledge and attitude scores between both study groups was 8.31 (p < 0.001) and 2.39 (p < 0.001), respectively. CONCLUSIONS: The level of knowledge and attitudes of secondary school children was shown to be acceptable prior to the intervention. Furthermore, a brief CPR training program improved their level of knowledge and attitudes significantly as compared to those who had never been trained