Membrane Porters of ATP-Binding Cassette Transport Systems Are Polyphyletic

The ATP-binding cassette (ABC) superfamily consists of both importers and exporters. These transporters have, by tradition, been classified according to the ATP hydrolyzing constituents, which are monophyletic. The evolutionary origins of the transmembrane porter proteins/domains are not known. Using five distinct computer programs, we here provide convincing statistical data suggesting that the transmembrane domains of ABC exporters are polyphyletic, having arisen at least three times independently. ABC1 porters arose by intragenic triplication of a primordial two-transmembrane segment (TMS)-encoding genetic element, yielding six TMS proteins. ABC2 porters arose by intragenic duplication of a dissimilar primordial three-TMS-encoding genetic element, yielding a distinctive protein family, nonhomologous to the ABC1 proteins. ABC3 porters arose by duplication of a primordial four-TMS-encoding genetic element, yielding either eight- or 10-TMS proteins. We assign each of 48 of the 50 currently recognized families of ABC exporters to one of the three evolutionarily distinct ABC types. Currently available high-resolution structural data for ABC porters are fully consistent with our findings. These results provide guides for future structural and mechanistic studies of these important transport systems

The COGs (context, object, and goals) in multisensory processing

Our understanding of how perception operates in real-world environments has been substantially advanced by studying both multisensory processes and “top-down” control processes influencing sensory processing via activity from higher-order brain areas, such as attention, memory, and expectations. As the two topics have been traditionally studied separately, the mechanisms orchestrating real-world multisensory processing remain unclear. Past work has revealed that the observer’s goals gate the influence of many multisensory processes on brain and behavioural responses, whereas some other multisensory processes might occur independently of these goals. Consequently, other forms of top-down control beyond goal dependence are necessary to explain the full range of multisensory effects currently reported at the brain and the cognitive level. These forms of control include sensitivity to stimulus context as well as the detection of matches (or lack thereof) between a multisensory stimulus and categorical attributes of naturalistic objects (e.g. tools, animals). In this review we discuss and integrate the existing findings that demonstrate the importance of such goal-, object- and context-based top-down control over multisensory processing. We then put forward a few principles emerging from this literature review with respect to the mechanisms underlying multisensory processing and discuss their possible broader implications

Lactate in the brain: from metabolic end-product to signalling molecule.

Lactate in the brain has long been associated with ischaemia; however, more recent evidence shows that it can be found there under physiological conditions. In the brain, lactate is formed predominantly in astrocytes from glucose or glycogen in response to neuronal activity signals. Thus, neurons and astrocytes show tight metabolic coupling. Lactate is transferred from astrocytes to neurons to match the neuronal energetic needs, and to provide signals that modulate neuronal functions, including excitability, plasticity and memory consolidation. In addition, lactate affects several homeostatic functions. Overall, lactate ensures adequate energy supply, modulates neuronal excitability levels and regulates adaptive functions in order to set the 'homeostatic tone' of the nervous system