X-ray structure of the metastable SEPT14-SEPT7 coiled coil reveals a hendecad region crucial for heterodimerization.

Septins are membrane-associated, GTP-binding proteins that are present in most eukaryotes. They polymerize to play important roles as scaffolds and/or diffusion barriers as part of the cytoskeleton. α-Helical coiled-coil domains are believed to contribute to septin assembly, and those observed in both human SEPT6 and SEPT8 form antiparallel homodimers. These are not compatible with their parallel heterodimeric organization expected from the current model for protofilament assembly, but they could explain the interfilament cross-bridges observed by microscopy. Here, the first structure of a heterodimeric septin coiled coil is presented, that between SEPT14 and SEPT7; the former is a SEPT6/SEPT8 homolog. This new structure is parallel, with two long helices that are axially shifted by a full helical turn with reference to their sequence alignment. The structure also has unusual knobs-into-holes packing of side chains. Both standard seven-residue (heptad) and the less common 11-residue (hendecad) repeats are present, creating two distinct regions with opposite supercoiling, which gives rise to an overall straight coiled coil. Part of the hendecad region is required for heterodimerization and therefore may be crucial for selective septin recognition. These unconventional sequences and structural features produce a metastable heterocomplex that nonetheless has enough specificity to promote correct protofilament assembly. For instance, the lack of supercoiling may facilitate unzipping and transitioning to the antiparallel homodimeric state.

Conciencia de la consciencia durante la anestesia / Awareness of consciousness during anesthesia

Resumen: La definición de consciencia en sí encierra una gran dificultad por su esencia y la inmensa complejidad de los numerosos componentes y procesos que la conforman. La consciencia como característica inherente al ser humano ha sido objeto de numerosos estudios y tratados, no sólo científicos, sino además filosóficos, religiosos, éticos, etcétera. Esto también incluye la diferencia entre consciencia y conciencia. La dificultad para poder establecer el principio que da origen a la consciencia, representa, por lo tanto, un gran reto para poder dilucidar con certeza lo que sucede con ésta durante el evento anestésico. Gracias al entendimiento que se va logrando a través de las investigaciones concernientes a las funciones de diferentes y complejas estructuras, tales como la substancia activadora reticular ascendente, el tálamo, partes del cuerpo estriado y la corteza cerebral, entre otras, que se relacionan gracias a la existencia de redes neuronales, integradas a su vez por nodos con funciones específicas y a la vez variadas, capaces de intercomunicar estas estructuras encefálicas, aun estando distantes, se tiene ahora nociones sólidas de dónde, cómo y cuánto se puede ver afectada la integración de la consciencia como consecuencia del efecto de los diferentes anestésicos.

Abstract: To define consciousness per se, involves a great difficulty because of its essence and the huge complexity regarding the great number of its components and the processes within. Consciousness, as a human characteristic, has been matter of large researching not only through a scientific approach, but also from the perspective of philosophic, religious, ethics investigations among others, including the distinction between consciousness and awareness. The trouble to define the foundation of consciousness implies a great challenge to get to know, what is happening during the anesthesia period. Through the understanding that has been accomplished by way of investigations concerning the different and complex functions of diverse neural structures such as the brain stem reticular formation, the thalamus, some parts of the striatum and the cerebral cortex among others, how they become connected by the neuronal nets who are compounded by nodes that have not only specific but a wide array of functions, capable of interconnect all these encephalic structures, even though they are far away, we know now with a good amount of certainty, where, how and how much the integrity of consciousness can be affected as a consequence of the different anesthetics effect.

Dynamic functional connectivity and brain metastability during altered states of consciousness.

The scientific study of human consciousness has greatly benefited from the development of non-invasive brain imaging methods. The quest to identify the neural correlates of consciousness combined psychophysical experimentation with neuroimaging tools such as functional magnetic resonance imaging (fMRI) to map the changes in neural activity associated with conscious vs. unconscious percepts. Different neuroimaging methods have also been applied to characterize spontaneous brain activity fluctuations during altered states of consciousness, and to develop quantitative metrics for the level of consciousness. Most of these studies, however, have not explored the dynamic nature of the whole-brain imaging data provided by fMRI. A series of empirical and computational studies strongly suggests that the temporal fluctuations observed in this data present a non-trivial structure, and that this structure is compatible with the exploration of a discrete repertoire of states. In this review we focus on how dynamic neuroimaging can be used to address theoretical accounts of consciousness based on the hypothesis of a dynamic core, i.e. a constantly evolving and transiently stable set of coordinated neurons that constitute an integrated and differentiated physical substrate for each conscious experience. We review work exploring the possibility that metastability in brain dynamics leads to a repertoire of dynamic core states, and discuss how it might be modified during altered states of consciousness. This discussion prompts us to review neuroimaging studies aimed to map the dynamic exploration of the repertoire of states as a function of consciousness. Complementary studies of the dynamic core hypothesis using perturbative methods are also discussed. Finally, we propose that a link between metastability in brain dynamics and the level of consciousness could pave the way towards a mechanistic understanding of altered states of consciousness using tools from dynamical systems theory and statistical physics.