Brain networks of novelty-driven involuntary and cued voluntary auditory attention shifting

In everyday life, we need a capacity to flexibly shift attention between alternative sound sources. However, relatively little work has been done to elucidate the mechanisms of attention shifting in the auditory domain. Here, we used a mixed event-related/sparse-sampling fMRI approach to investigate this essential cognitive function. In each 10-sec trial, subjects were instructed to wait for an auditory "cue" signaling the location where a subsequent "target" sound was likely to be presented. The target was occasionally replaced by an unexpected "novel" sound in the uncued ear, to trigger involuntary attention shifting. To maximize the attention effects, cues, targets, and novels were embedded within dichotic 800-Hz vs. 1500-Hz pure-tone "standard" trains. The sound of clustered fMRI acquisition (starting at t?=?7.82 sec) served as a controlled trial-end signal. Our approach revealed notable activation differences between the conditions. Cued voluntary attention shifting activated the superior intra--parietal sulcus (IPS), whereas novelty-triggered involuntary orienting activated the inferior IPS and certain subareas of the precuneus. Clearly more widespread activations were observed during voluntary than involuntary orienting in the premotor cortex, including the frontal eye fields. Moreover, we found -evidence for a frontoinsular-cingular attentional control network, consisting of the anterior insula, inferior frontal cortex, and medial frontal cortices, which were activated during both target discrimination and voluntary attention shifting. Finally, novels and targets activated much wider areas of superior temporal auditory cortices than shifting cues.     

Greeting,aggression, and coalitions between male baboons: Demographic correlates

Interactions of asymmetrical, symmetrical, and unreciprocated greeting, and episodes of aggression and coalitions observed between 18 males, members of a large multi-harem colony of baboons (Papio hamadryas, P. cynocephalus, and their hybrids) housed in the Madrid Zoo, were recorded throughout 11 time blocks between January 1983 and March 1985. The major question investigated was whether the demographic characteristics of the colony affected the frequency with which males used three behavioural strategies, namely, greeting, aggression, and coalitions. It was found that under demographic conditions eliciting more intense male-male competition, for example, when the ratio of oestrous cycles per adult male was lower, males exchanged frequent greetings, especially the symmetrical form (i.e. notifying) and solicited more coalitions, but did not show any significant change in rates of dyadic aggression. Male phenotype-related effects on rates of greeting and coalitions were found as well. Results are discussed in relation with the suggested role of greeting and of coalition behaviour as strategies used in the negotiation of changes in competitive social relationship (e.g. consort changeovers). These strategies are regarded as social tactics alternative to direct aggression.     

Power capping: a prelude to power shifting

We present a technique that controls the peak power consumption of a high-density server by implementing a feedback controller that uses precise, system-level power measurement to periodically select the highest performance state while keeping the system within a fixed power constraint. A control theoretic methodology is applied to systematically design this control loop with analytic assurances of system stability and controller performance, despite unpredictable workloads and running environments. In a real server we are able to control power over a 1 second period to within 1 W and over an 8 second period to within 0.1 W. Conventional servers respond to power supply constraint situations by using simple open-loop policies to set a safe performance level in order to limit peak power consumption. We show that closed-loop control can provide higher performance under these conditions and implement this technique on an IBM BladeCenter HS20 server. Experimental results demonstrate that closed-loop control provides up to 82% higher application performance compared to open-loop control and up to 17% higher performance compared to a widely used ad-hoc technique.

Prespecification and plasticity: shifting mechanisms of cell migration

Cell migration is a universal process involving different morphologies and mechanisms in different cell types and tissue environments. Prespecified cell-type-specific patterns of cell migration can be classified into single cell migration (amoeboid, mesenchymal) and collective migration modes (cell sheets, strands, tubes, clusters). These intrinsic molecular programs are associated with a characteristic structure of the actin cytoskeleton, as well as the cell-type-specific use of integrins, matrix-degrading enzymes (matrix metalloproteinases and serine proteases), cell-cell adhesion molecules (cadherins and activated leukocyte adhesion molecule), and signaling towards the cytoskeleton (carried out by RHO GTPases). In response to the gain or loss of these key molecular determinants, significant adaptation reactions can modify the cell's shape, pattern, and migration mechanism; examples of this include the epithelial-mesenchymal transition, mesenchymal-amoeboid transition and collective-amoeboid transition.     

Protein sorting in the Golgi complex: shifting paradigms

The paradigms for transport along the biosynthetic route have changed dramatically over the past 15 years. Unlike the situation 15 years ago, the current paradigm involves sorting signals practically at every step of the pathway. In particular, at the exit from the Golgi complex, apical, basolateral and lysosomal targeting signals result in the generation of a variety of routes. Furthermore, it is now quite clear that not all sorting in the biosynthetic route occurs in the Golgi complex or the Trans Golgi Network (TGN). Sorting may occur distally to the Golgi, in recycling endosomes or in budded tubulosaccular structures, or it may occur proximally to the Golgi complex, at the exit from the ER. Several adaptors are candidates to sort apical and basolateral proteins but only AP1B and AP4 are currently involved. Progress is fast and future work should elucidate many of the open questions.     

Health research in Canada: a shifting paradigm.

A personal review of medical research in Canadian medical schools over the past 25 years reveals extraordinary contributions. Over this time, medical research evolved from a by-product of faculty members to a commitment that determines the future success of a medical faculty. The increasing competition for health research funding and the high standards created internationally have changed the way research is organized in our medical faculties. Current trends include a move toward group and thematic research, an increased role of research institutes and the development of strategic partnerships with industry. Because of the need for more planning and more critical and timely review of research efforts, the benefits of collaboration enhance the quality and competitiveness of a medical faculty. A broadened vision of the Medical Research Council and provincial foundations and the need to increase resources for research foreshadow even greater change.     

Tyrosine phosphorylation in semaphorin signalling: shifting into overdrive

The semaphorins constitute a large family of molecular signals with regulatory functions in neuronal development, angiogenesis, cancer progression and immune responses. Accumulating data indicate that semaphorins might trigger multiple signalling pathways, and mediate different and sometimes opposing effects, depending on the cellular context and the particular plexin-associated subunits of the receptor complex, which can include receptor-type or cytoplasmic tyrosine kinases such as MET, ERBB2, VEGFR2, FYN, FES, PYK2 and SRC. It has also been shown that a specific plexin can alternatively associate with different tyrosine kinase receptors, eliciting divergent signalling pathways and functional outcomes. Tyrosine phosphorylation is a pivotal post-translational protein modification that regulates intracellular signalling. Therefore, phosphorylation of tyrosines in the intracellular domain of plexins could determine or modify their interactions with additional signal transducers. Here, we discuss the potential relevance of tyrosine phosphorylation in semaphorin-induced signalling, with an emphasis on its probable role in dictating the choice between multiple pathways and functional outcomes. The identification of implicated tyrosine kinases will pave the way to target individual semaphorin-mediated functions.     

The spliceosome: caught in a web of shifting interactions

Splicing is a crucial, ubiquitous and highly complex step in eukaryotic gene expression. The daunting complexity of the splicing reaction, although fascinating, has severely limited our understanding of its mechanistic details. Recent advances have begun to provide exciting new insights into the dynamic interactions that govern the function of the spliceosome, the multi-megadalton complex that performs splicing. An emerging paradigm is the presence of a succession of distinct conformational states, which are stabilized by an intricate network of interactions. Recent data suggest that even subtle changes in the composition of the interaction network can result in interconversion of the different conformational states, providing opportunities for regulation and proofreading of spliceosome function. Significant progress in proteomics has elucidated the protein composition of the spliceosome at different stages of assembly. Also, the increased sophistication and resolution of cryo-electron microscopy techniques, combined with high-resolution structural studies on a smaller scale, promise to create detailed images of the global structure of the spliceosome and its main components, which in turn will provide a plethora of mechanistic insights. Overall, the past two years have seen a convergence of data from different lines of research into what promises to become a holistic picture of spliceosome function.     

Protein-protein interaction networks: from interactions to networks

The goal of interaction proteomics that studies the protein-protein interactions of all expressed proteins is to understand biological processes that are strictly regulated by these interactions. The availability of entire genome sequences of many organisms and high-throughput analysis tools has led scientists to study the entire proteome (Pandey and Mann, 2000). There are various high-throughput methods for detecting protein interactions such as yeast two-hybrid approach and mass spectrometry to produce vast amounts of data that can be utilized to decipher protein functions in complicated biological networks. In this review, we discuss recent developments in analytical methods for large-scale protein interactions and the future direction of interaction proteomics.     

Stoichiometry of endothermy: shifting the quest from nitrogen to carbon

For many animals, notably herbivores, plants are often an inadequate food source given the low content of protein and high content of C-rich material. This conception is mainly based on studies on ectotherms. The validity of this conception for endotherms is unclear given their much higher carbon requirements for maintenance energy metabolism than ectotherms. Applying stoichiometric principles, we hypothesized that endotherms can cope with diets with much higher (metabolizable) carbon to nitrogen ratios than ectotherms. Using empirical data on birds, eutherian mammals, marsupials and reptiles, we compiled and compared measurements and allometric equations for energy metabolism as well as nitrogen requirements. Our analysis supports our hypothesis that plants, and especially their leaves, are generally sufficiently rich in nitrogen to fulfil protein demands in endotherms, at least during maintenance conditions, but less so in ectotherms. This has important implications with respect to community functioning and the evolution of endothermy.     

Genes, copying, and female mate choice: shifting thresholds

Recent experimental work on guppies (Poecilia reticulata) hasexamined the strength of genetic and cultural (copying) factorsin determining female mate choice. Using females from a populationwith a heritable preference for the amount of orange body colorpossessed by males, prior work discovered that a threshold differencein orange color among males existed below which females wouldchoose a less orange male if they observed another female choosethat male, but above which they consistently preferred the moreorange of the males, regardless of whether they viewed anotherfemale prefer the less orange male. I tested whether this thresholdcan be shifted by increasing the amount of mate-copying informationavailable to a female. I demonstrate that when a female hasthe opportunity to see two different model females independentlyprefer the less orange of two males or a single female neara drab male for a longer period of time (twice as long as inprior work), the observer female prefers this drab male evenwhen males dramatically differ in orange coloration.