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.     

Attempting to distinguish between endogenous and contaminating cytokeratins in a corneal proteomic study

Background  

The observation of cytokeratins (CK's) in mass spectrometry based studies raises the question of whether the identified CK is a true endogenous protein from the sample or simply represents a contaminant. This issue is especially important in proteomic studies of the corneal epithelium where several CK's have previously been reported to mark the stages of differentiation from corneal epithelial stem cell to the differentiated cell.     

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.     

Male sexual dysfunction and infertility associated with neurological disorders

Normal sexual and reproductive functions depend largely on neurological mechanisms. Neurological defects in men can cause infertility through erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Among the major conditions contributing to these symptoms are pelvic and retroperitoneal surgery, diabetes, congenital spinal abnormalities, multiple sclerosis and spinal cord injury. Erectile dysfunction can be managed by an increasingly invasive range of treatments including medications, injection therapy and the surgical insertion of a penile implant. Retrograde ejaculation is managed by medications to reverse the condition in mild cases and in bladder harvest of semen after ejaculation in more severe cases. Anejaculation might also be managed by medication in mild cases while assisted ejaculatory techniques including penile vibratory stimulation and electroejaculation are used in more severe cases. If these measures fail, surgical sperm retrieval can be attempted. Ejaculation with penile vibratory stimulation can be done by some spinal cord injured men and their partners at home, followed by in-home insemination if circumstances and sperm quality are adequate. The other options always require assisted reproductive techniques including intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection. The method of choice depends largely on the number of motile sperm in the ejaculate.