Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers

We present a review of the interplay between the evolution of circumstellar disks and the formation of planets, both from the perspective of theoretical models and dedicated observations. Based on this, we identify and discuss fundamental questions concerning the formation and evolution of circumstellar disks and planets which can be addressed in the near future with optical and infrared long-baseline interferometers. Furthermore, the importance of complementary observations with long-baseline (sub)millimeter interferometers and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics Review"; The final publication is available at http://www.springerlink.co

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Phage-mediated horizontal transfer of a Staphylococcus aureus virulence-associated genomic island

Staphylococcus aureus is a major pathogen of humans and animals. The capacity of S. aureus to adapt to different host species and tissue types is strongly influenced by the acquisition of mobile genetic elements encoding determinants involved in niche adaptation. The genomic islands νSaα and νSaβ are found in almost all S. aureus strains and are characterized by extensive variation in virulence gene content. However the basis for the diversity and the mechanism underlying mobilization of the genomic islands between strains are unexplained. Here, we demonstrated that the genomic island, νSaβ, encoding an array of virulence factors including staphylococcal superantigens, proteases, and leukotoxins, in addition to bacteriocins, was transferrable in vitro to human and animal strains of multiple S. aureus clones via a resident prophage. The transfer of the νSaβ appears to have been accomplished by multiple conversions of transducing phage particles carrying overlapping segments of the νSaβ. Our findings solve a long-standing mystery regarding the diversification and spread of the genomic island νSaβ, highlighting the central role of bacteriophages in the pathogenic evolution of S. aureus

Mobilization of genomic islands of Staphylococcus aureus by temperate bacteriophage

The virulence of Staphylococcus aureus, in both human and animal hosts, is largely influenced by the acquisition of mobile genetic elements (MGEs). Most S. aureus strains carry a variety of MGEs, including three genomic islands (νSaα, νSaβ, νSaγ) that are diverse in virulence gene content but conserved within strain lineages. Although the mobilization of pathogenicity islands, phages and plasmids has been well studied, the mobilization of genomic islands is poorly understood. We previously demonstrated the mobilization of νSaβ by the adjacent temperate bacteriophage ϕSaBov from strain RF122. In this study, we demonstrate that ϕSaBov mediates the mobilization of νSaα and νSaγ, which are located remotely from ϕSaBov, mostly to recipient strains belonging to ST151. Phage DNA sequence analysis revealed that chromosomal DNA excision events from RF122 were highly specific to MGEs, suggesting sequence-specific DNA excision and packaging events rather than generalized transduction by a temperate phage. Disruption of the int gene in ϕSaBov did not affect phage DNA excision, packaging, and integration events. However, disruption of the terL gene completely abolished phage DNA packing events, suggesting that the primary function of temperate phage in the transfer of genomic islands is to allow for phage DNA packaging by TerL and that transducing phage particles are the actual vehicle for transfer. These results extend our understanding of the important role of bacteriophage in the horizontal transfer and evolution of genomic islands in S. aureus

Fundamental differences in patterns of retinal ageing between primates and mice

Photoreceptors have high metabolic demands and age rapidly, undermining visual function. We base our understanding mainly on ageing mice where elevated inflammation, extracellular deposition, including that of amyloid beta, and rod and cone photoreceptor loss occur, but cones are not lost in ageing primate although their function declines, revealing that primate and mouse age differently. We examine ageing primate retinae and show elevated stress but low inflammation. However, aged primates have a >70% reduction in adenosine triphosphate (ATP) and a decrease in cytochrome c oxidase. There is a shift in cone mitochondrial positioning and glycolytic activity increases. Bruch’s membrane thickens but unlike in mice, amyloid beta is absent. Hence, reduced ATP may explain cone functional decline in ageing but their retained presence offers the possibility of functional restoration if they can be fuelled appropriately to restore cellular function. This is important because as humans we largely depend on cone function to see and are rarely fully dark adapted. Presence of limited aged inflammation and amyloid beta deposition question some of the therapeutic approaches taken to resolve problems of retinal ageing in humans and the possible lack of success in clinical trials in macular degeneration that have targeted inflammatory agents

Evaluation of an Activated Patient Diabetes Education Newsletter

This study evaluated a monthly; activated patient newsletter sent to over 7000 patients in Michigan with diabetes. The newsletter provided concise and action-oriented information about diabetes care. Patients who had signed up to receive the newsletter during the first 4 months of the project (1863) were surveyed to determine how many patients found the newsletter helpful; 80% (1498) of the patients replied. Patients who found the newsletter most helpful were older, had lower incomes, and reported more corrtplications, less understanding of diabetes, and being in poorer overall health. They also were more likely to have non-insulin-dependent diabetes mellitus (NIDDM) than insulin-dependent diabetes mellitus (IDDM). We concluded that the activated patient newsletter is a useful public health/patient education intervention for persons with diabetes. Such a newsletter should be part of a coordinated system of ongoing patient care, education, screening, and social and psychological support.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68904/2/10.1177_014572179402000106.pd

The Neural Representation of Prospective Choice during Spatial Planning and Decisions

We are remarkably adept at inferring the consequences of our actions, yet the neuronal mechanisms that allow us to plan a sequence of novel choices remain unclear. We used functional magnetic resonance imaging (fMRI) to investigate how the human brain plans the shortest path to a goal in novel mazes with one (shallow maze) or two (deep maze) choice points. We observed two distinct anterior prefrontal responses to demanding choices at the second choice point: one in rostrodorsal medial prefrontal cortex (rd-mPFC)/superior frontal gyrus (SFG) that was also sensitive to (deactivated by) demanding initial choices and another in lateral frontopolar cortex (lFPC), which was only engaged by demanding choices at the second choice point. Furthermore, we identified hippocampal responses during planning that correlated with subsequent choice accuracy and response time, particularly in mazes affording sequential choices. Psychophysiological interaction (PPI) analyses showed that coupling between the hippocampus and rd-mPFC increases during sequential (deep versus shallow) planning and is higher before correct versus incorrect choices. In short, using a naturalistic spatial planning paradigm, we reveal how the human brain represents sequential choices during planning without extensive training. Our data highlight a network centred on the cortical midline and hippocampus that allows us to make prospective choices while maintaining initial choices during planning in novel environments

Dopamine, affordance and active inference.

The role of dopamine in behaviour and decision-making is often cast in terms of reinforcement learning and optimal decision theory. Here, we present an alternative view that frames the physiology of dopamine in terms of Bayes-optimal behaviour. In this account, dopamine controls the precision or salience of (external or internal) cues that engender action. In other words, dopamine balances bottom-up sensory information and top-down prior beliefs when making hierarchical inferences (predictions) about cues that have affordance. In this paper, we focus on the consequences of changing tonic levels of dopamine firing using simulations of cued sequential movements. Crucially, the predictions driving movements are based upon a hierarchical generative model that infers the context in which movements are made. This means that we can confuse agents by changing the context (order) in which cues are presented. These simulations provide a (Bayes-optimal) model of contextual uncertainty and set switching that can be quantified in terms of behavioural and electrophysiological responses. Furthermore, one can simulate dopaminergic lesions (by changing the precision of prediction errors) to produce pathological behaviours that are reminiscent of those seen in neurological disorders such as Parkinson's disease. We use these simulations to demonstrate how a single functional role for dopamine at the synaptic level can manifest in different ways at the behavioural level

Neural correlates of evidence accumulation during value-based decisions revealed via simultaneous EEG-fMRI

Current computational accounts posit that, in simple binary choices, humans accumulate evidence in favour of the different alternatives before committing to a decision. Neural correlates of this accumulating activity have been found during perceptual decisions in parietal and prefrontal cortex; however the source of such activity in value-based choices remains unknown. Here we use simultaneous EEG–fMRI and computational modelling to identify EEG signals reflecting an accumulation process and demonstrate that the within- and across-trial variability in these signals explains fMRI responses in posterior-medial frontal cortex. Consistent with its role in integrating the evidence prior to reaching a decision, this region also exhibits task-dependent coupling with the ventromedial prefrontal cortex and the striatum, brain areas known to encode the subjective value of the decision alternatives. These results further endorse the proposition of an evidence accumulation process during value-based decisions in humans and implicate the posterior-medial frontal cortex in this process

Mechanisms and therapeutic applications of electromagnetic therapy in Parkinson's disease

© 2015 Vadalà et al. Electromagnetic therapy is a non-invasive and safe approach for the management of several pathological conditions including neurodegenerative diseases. Parkinson's disease is a neurodegenerative pathology caused by abnormal degeneration of dopaminergic neurons in the ventral tegmental area and substantia nigra pars compacta in the midbrain resulting in damage to the basal ganglia. Electromagnetic therapy has been extensively used in the clinical setting in the form of transcranial magnetic stimulation, repetitive transcranial magnetic stimulation, high-frequency transcranial magnetic stimulation and pulsed electromagnetic field therapy which can also be used in the domestic setting. In this review, we discuss the mechanisms and therapeutic applications of electromagnetic therapy to alleviate motor and non-motor deficits that characterize Parkinson's disease