Frontal eye fields involved in shifting frame of reference within working memory for scenes

Working memory (WM) evoked by linguistic cues for allocentric spatial and egocentric spatial aspects of a visual scene was investigated by correlating fMRI BOLD signal (or "activation") with performance on a spatial-relations task. Subjects indicated the relative positions of a person or object (referenced by the personal pronouns "he/she/it") in a previously shown image relative to either themselves (egocentric reference frame) or shifted to a reference frame anchored in another person or object in the image (allocentric reference frame), e.g. "Was he in front of you/her?" Good performers had both shorter response time and more correct responses than poor performers in both tasks. These behavioural variables were entered into a principal component analysis. The first component reflected generalised performance level. We found that the frontal eye fields (FEF), bilaterally, had a higher BOLD response during recall involving allocentric compared to egocentric spatial reference frames, and that this difference was larger in good performers than in poor performers as measured by the first behavioural principal component. The frontal eye fields may be used when subjects move their internal gaze during shifting reference frames in representational space. Analysis of actual eye movements in three subjects revealed no difference between egocentric and allocentric recall tasks where visual stimuli were also absent. Thus, the FEF machinery for directing eye movements may also be involved in changing reference frames within WM.     

Music in minor activates limbic structures: a relationship with dissonance?

Using functional magnetic resonance imaging, we contrasted major and minor mode melodies controlled for liking to study the neural basis of musical mode perception. To examine the influence of the larger dissonance in minor melodies on neural activation differences, we further introduced a strongly dissonant stimulus, in the form of a chromatic scale. Minor mode melodies were evaluated as sadder than major melodies, and in comparison they caused increased activity in limbic structures, namely left parahippocampal gyrus, bilateral ventral anterior cingulate, and in left medial prefrontal cortex. Dissonance explained some, but not all, of the heightened activity in the limbic structures when listening to minor mode music.     

Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups

Background  

A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, ERCC1, ERCC2, and PPP1R13L (aka RAI) are related to DNA repair and cell survival, and one, CD3EAP, aka ASE1, may be related to cell proliferation. The whole region seems related to the cellular response to external damaging agents and markers in it are associated with risk of several cancers.     

Once-Weekly GLP-1 Agonists: How Do They Differ from Exenatide and Liraglutide?

Incretin mimetics offer a new modality in diabetes treatment. This modality is based on the effects of the naturally occurring glucoregulatory gut hormone glucagon-like peptide-1 (GLP-1), which counteracts several pathophysiologic traits in type 2 diabetes. GLP-1 receptor agonists with extended half-lives entailing fewer injections and presumably an improved throughout-the-day glycemic control are in clinical development. This article summarizes the physiologic effects of GLP-1; the effects of the already marketed GLP-1 analogues for daily dosing, exenatide and liraglutide; and reviews the presently published data (with emphasis on clinical pharmacokinetics, efficacy, and safety) on GLP-1 agonists, which currently are in development and intended for once-weekly dosing: albiglutide/albugon, CJC-1131, CJC-1134-PC, exenatide once weekly, and taspoglutide.     

One-step assembly in yeast of 25 overlapping DNA fragments to form a complete synthetic Mycoplasma genitalium genome

We previously reported assembly and cloning of the synthetic Mycoplasma genitalium JCVI-1.0 genome in the yeast Saccharomyces cerevisiae by recombination of six overlapping DNA fragments to produce a 592-kb circle. Here we extend this approach by demonstrating assembly of the synthetic genome from 25 overlapping fragments in a single step. The use of yeast recombination greatly simplifies the assembly of large DNA molecules from both synthetic and natural fragments.     

Quantitative characterization of magnetic separators: Comparison of systems with and without integrated microfluidic mixers

We present two new types of microfluidic passive magnetic bead separator systems as well as methods for performing quantitative characterizations of them. Both systems consist of a microfluidic channel with long rectangular magnetic elements of permalloy that are placed by the sides of the channel and magnetized by an external magnetic field. In one of the systems, a staggered herringbone microfluidic mixer is integrated in the channel. The characterization of the systems includes magnetic measurements of the capture-and-release efficiencies, estimates of distributions of captured beads in a channel from micrographs, and simulations and analytical models of bead trajectories, capture efficiencies, and capture distributions. We show that the efficiencies of both systems compare favorably to those in the literature. For the studied geometries, the mixer is demonstrated to increase the bead capture-and-release efficiency for a fixed flow rate by up to a factor of two. Moreover, high capture efficiencies can be achieved in the system with mixer at up to ten times higher flow rates than in the system without mixer.     

CTL epitopes for influenza A including the H5N1 bird flu; genome-, pathogen-, and HLA-wide screening

The purpose of the present study is to perform a global screening for new immunogenic HLA class I (HLA-I) restricted cytotoxic T cell (CTL) epitopes of potential utility as candidates of influenza A-virus diagnostics and vaccines. We used predictions of antigen processing and presentation, the latter encompassing 12 different HLA class I supertypes with >99% population coverage, and searched for conserved epitopes from available influenza A viral protein sequences. Peptides corresponding to 167 predicted peptide-HLA-I interactions were synthesized, tested for peptide-HLA-I interactions in a biochemical assay and for influenza-specific, HLA-I-restricted CTL responses in an IFN-gamma ELISPOT assay. Eighty-nine peptides could be confirmed as HLA-I binders, and 13 could be confirmed as CTL targets. The 13 epitopes, are highly conserved among human influenza A pathogens, and all of these epitopes are present in the emerging bird flu isolates. Our study demonstrates that present technology enables a fast global screening for T cell immune epitopes of potential diagnostics and vaccine interest. This technology includes immuno-bioinformatics predictors with the capacity to perform fast genome-, pathogen-, and HLA-wide searches for immune targets. To exploit this new potential, a coordinated international effort to analyze the precious source of information represented by rare patients, such as the current victims of bird flu, would be essential.