Quantitative electroencephalography reveals different physiological profiles between benign and remitting-relapsing multiple sclerosis patients

<p>Abstract</p> <p>Background</p> <p>A possible method of finding physiological markers of multiple sclerosis (MS) is the application of EEG quantification (QEEG) of brain activity when the subject is stressed by the demands of a cognitive task. In particular, modulations of the spectral content that take place in the EEG of patients with multiple sclerosis remitting-relapsing (RRMS) and benign multiple sclerosis (BMS) during a visuo-spatial task need to be observed.</p> <p>Methods</p> <p>The sample consisted of 19 patients with RRMS, 10 with BMS, and 21 control subjects. All patients were free of medication and had not relapsed within the last month. The power spectral density (PSD) of different EEG bands was calculated by Fast-Fourier-Transformation (FFT), those analysed being delta, theta, alpha, beta and gamma. Z-transformation was performed to observe individual profiles in each experimental group for spectral modulations. Lastly, correlation analyses was performed between QEEG values and other variables from participants in the study (age, EDSS, years of evolution and cognitive performance).</p> <p>Results</p> <p>Nearly half (42%) the RRMS patients showed a statistically significant increase of two or more standard deviations (SD) compared to the control mean value for the beta-2 and gamma bands (F = 2.074, p = 0.004). These alterations were localized to the anterior regions of the right hemisphere, and bilaterally to the posterior areas of the scalp. None of the BMS patients or control subjects had values outside the range of ± 2 SD. There were no significant correlations between these values and the other variables analysed (age, EDSS, years of evolution or behavioural performance).</p> <p>Conclusion</p> <p>During the attentional processing, changes in the high EEG spectrum (beta-2 and gamma) in MS patients exhibit physiological alterations that are not normally detected by spontaneous EEG analysis. The different spectral pattern between pathological and controls groups could represent specific changes for the RRMS patients, indicative of compensatory mechanisms or cortical excitatory states representative of some phases during the RRMS course that are not present in the BMS group.</p

Global quantification of mammalian gene expression control

Gene expression is a multistep process that involves the transcription, translation and turnover of messenger RNAs and proteins. Although it is one of the most fundamental processes of life, the entire cascade has never been quantified on a genome-wide scale. Here we simultaneously measured absolute mRNA and protein abundance and turnover by parallel metabolic pulse labelling for more than 5,000 genes in mammalian cells. Whereas mRNA and protein levels correlated better than previously thought, corresponding half-lives showed no correlation. Using a quantitative model we have obtained the first genome-scale prediction of synthesis rates of mRNAs and proteins. We find that the cellular abundance of proteins is predominantly controlled at the level of translation. Genes with similar combinations of mRNA and protein stability shared functional properties, indicating that half-lives evolved under energetic and dynamic constraints. Quantitative information about all stages of gene expression provides a rich resource and helps to provide a greater understanding of the underlying design principles

Diffusion of Myosin V on Microtubules: A Fine-Tuned Interaction for Which E-Hooks Are Dispensable

Organelle transport in eukaryotes employs both microtubule and actin tracks to deliver cargo effectively to their destinations, but the question of how the two systems cooperate is still largely unanswered. Recently, in vitro studies revealed that the actin-based processive motor myosin V also binds to, and diffuses along microtubules. This biophysical trick enables cells to exploit both tracks for the same transport process without switching motors. The detailed mechanisms underlying this behavior remain to be solved. By means of single molecule Total Internal Reflection Microscopy (TIRFM), we show here that electrostatic tethering between the positively charged loop 2 and the negatively charged C-terminal E-hooks of microtubules is dispensable. Furthermore, our data indicate that in addition to charge-charge interactions, other interaction forces such as non-ionic attraction might account for myosin V diffusion. These findings provide evidence for a novel way of myosin tethering to microtubules that does not interfere with other E-hook-dependent processes

Genome and Transcriptome Analysis of the Food-Yeast Candida utilis

The industrially important food-yeast Candida utilis is a Crabtree effect-negative yeast used to produce valuable chemicals and recombinant proteins. In the present study, we conducted whole genome sequencing and phylogenetic analysis of C. utilis, which showed that this yeast diverged long before the formation of the CUG and Saccharomyces/Kluyveromyces clades. In addition, we performed comparative genome and transcriptome analyses using next-generation sequencing, which resulted in the identification of genes important for characteristic phenotypes of C. utilis such as those involved in nitrate assimilation, in addition to the gene encoding the functional hexose transporter. We also found that an antisense transcript of the alcohol dehydrogenase gene, which in silico analysis did not predict to be a functional gene, was transcribed in the stationary-phase, suggesting a novel system of repression of ethanol production. These findings should facilitate the development of more sophisticated systems for the production of useful reagents using C. utilis

Transcriptome-Wide Binding Sites for Components of the Saccharomyces cerevisiae Non-Poly(A) Termination Pathway: Nrd1, Nab3, and Sen1

RNA polymerase II synthesizes a diverse set of transcripts including both protein-coding and non-coding RNAs. One major difference between these two classes of transcripts is the mechanism of termination. Messenger RNA transcripts terminate downstream of the coding region in a process that is coupled to cleavage and polyadenylation reactions. Non-coding transcripts like Saccharomyces cerevisiae snoRNAs terminate in a process that requires the RNA–binding proteins Nrd1, Nab3, and Sen1. We report here the transcriptome-wide distribution of these termination factors. These data sets derived from in vivo protein–RNA cross-linking provide high-resolution definition of non-poly(A) terminators, identify novel genes regulated by attenuation of nascent transcripts close to the promoter, and demonstrate the widespread occurrence of Nrd1-bound 3′ antisense transcripts on genes that are poorly expressed. In addition, we show that Sen1 does not cross-link efficiently to many expected non-coding RNAs but does cross-link to the 3′ end of most pre–mRNA transcripts, suggesting an extensive role in mRNA 3′ end formation and/or termination

Quantitative Multicolor Super-Resolution Microscopy Reveals Tetherin HIV-1 Interaction

Virus assembly and interaction with host-cell proteins occur at length scales below the diffraction limit of visible light. Novel super-resolution microscopy techniques achieve nanometer resolution of fluorescently labeled molecules. The cellular restriction factor tetherin (also known as CD317, BST-2 or HM1.24) inhibits the release of human immunodeficiency virus 1 (HIV-1) through direct incorporation into viral membranes and is counteracted by the HIV-1 protein Vpu. For super-resolution analysis of HIV-1 and tetherin interactions, we established fluorescence labeling of HIV-1 proteins and tetherin that preserved HIV-1 particle formation and Vpu-dependent restriction, respectively. Multicolor super-resolution microscopy revealed important structural features of individual HIV-1 virions, virus assembly sites and their interaction with tetherin at the plasma membrane. Tetherin localization to micro-domains was dependent on both tetherin membrane anchors. Tetherin clusters containing on average 4 to 7 tetherin dimers were visualized at HIV-1 assembly sites. Combined biochemical and super-resolution analysis revealed that extended tetherin dimers incorporate both N-termini into assembling virus particles and restrict HIV-1 release. Neither tetherin domains nor HIV-1 assembly sites showed enrichment of the raft marker GM1. Together, our super-resolution microscopy analysis of HIV-1 interactions with tetherin provides new insights into the mechanism of tetherin-mediated HIV-1 restriction and paves the way for future studies of virus-host interactions