Effects of omega-3 fatty acids on arterial stiffness in patients with hypertension: a randomized pilot study.

BackgroundOmega-3 fatty acids prevent cardiovascular disease (CVD) events in patients with myocardial infarction or heart failure. Benefits in patients without overt CVD have not been demonstrated, though most studies did not use treatment doses (3.36 g) of omega-3 fatty acids. Arterial stiffness measured by pulse wave velocity (PWV) predicts CVD events independent of standard risk factors. However, no therapy has been shown to reduce PWV in a blood pressure-independent manner. We assessed the effects of esterified omega-3 fatty acids on PWV and serum markers of inflammation among patients with hypertension.Design and methodsWe performed a prospective, randomized; double-blinded pilot study of omega-3 fatty acids among 62 patients in an urban, safety net hospital. Patients received 3.36 g of omega-3 fatty acids vs. matched placebo daily for 3-months. The principal outcome measure was change in brachial-ankle PWV. Serum inflammatory markers associated with CVD risk were also assessed.ResultsThe majority (71 %) were of Latino ethnicity. After 3-months, mean change in arterial PWV among omega-3 and placebo groups was -97 cm/s vs. -33 cm/s respectively (p = 0.36 for difference, after multivariate adjustment for baseline age, systolic blood pressure, and serum adiponectin). Non-significant reductions in lipoprotein-associated phospholipase A2 (LpPLA2) mass and high sensitivity C-reactive protein (hsCRP) relative to placebo were also observed (p = 0.08, and 0.21, respectively).ConclusionHigh-dose omega-3 fatty acids did not reduce arterial PWV or markers of inflammation among patients within a Latino-predominant population with hypertension.Clinical trial registrationNCT00935766 , registered July 8 2009

The Role of Native Language and the Fundamental Design of the Auditory System in Detecting Rhythm Changes

Accepted December 13, 2018Purpose: We investigated whether rhythm discrimination is mainly driven by the native language of the listener or by the fundamental design of the human auditory system and universal cognitive mechanisms shared by all people irrespective of rhythmic patterns in their native language. Method: In multiple experiments, we asked participants to listen to 2 continuous acoustic sequences and to determine whether their rhythms were the same or different (AX discrimination). Participants were native speakers of 4 languages with different rhythmic properties (Spanish, French, English, and German) to understand whether the predominant rhythmic patterns of a native language affect sensitivity, bias, and reaction time in detecting rhythmic changes in linguistic (Experiment 2) and in nonlinguistic (Experiments 1 and 2) acoustic sequences. We examined sensitivity and bias measures, as well as reaction times. We also computed Bayes factors in order to assess the effect of native language. Results: All listeners performed better (i.e., responded faster and manifested higher sensitivity and accuracy) when detecting the presence or absence of a rhythm change when the 1st stimulus in an AX test pair exhibited regular rhythm (i.e., a syllable-timed rhythmic pattern) than when the 1st stimulus exhibited irregular rhythm (i.e., stress-timed rhythmic pattern). This result pattern was observed both on linguistic and nonlinguistic stimuli and was not modulated by the native language of the participant. Conclusion: We conclude that rhythm change detection is a fundamental function of a processing system that relies on general auditory mechanisms and is not modulated by linguistic experience.The authors acknowledge support from Spanish Ministry of Economy and Competitiveness Grant PSI2017-82563-P (awarded to A. G. S.), the “Severo Ochoa” Programme for Centres/Units of Excellence in R&D Grant SEV-2015-490 (BCBL), and the Basque Foundation for Science Grant IKERBASQUE (awarded to A. G. S. and M. O.). D. M. G. was supported by Grant PIA/Basal FB0003 from the Chilean Research Council. L. P. was supported by the Spanish Ministry of Economy and Competitiveness via Juan de la Cierva fellowship

The Quantum Modular Group in (2+1)-Dimensional Gravity

The role of the modular group in the holonomy representation of (2+1)-dimensional quantum gravity is studied. This representation can be viewed as a "Heisenberg picture", and for simple topologies, the transformation to the ADM "Schr{\"o}dinger picture" may be found. For spacetimes with the spatial topology of a torus, this transformation and an explicit operator representation of the mapping class group are constructed. It is shown that the quantum modular group splits the holonomy representation Hilbert space into physically equivalent orthogonal ``fundamental regions'' that are interchanged by modular transformations.Comment: 23 pages, LaTeX, no figures; minor changes and clarifications in response to referee (basic argument and conclusions unaffected

Increased localization of APP-C99 in mitochondria-associated ER membranes causes mitochondrial dysfunction in Alzheimer disease

In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid precursor protein (APP) is cleaved by beta-secretase to generate a 99-aa C-terminal fragment (C99) that is then cleaved by c-secretase to generate the beta-amyloid (Ab) found in senile plaques. In previous reports, we and others have shown that c-secretase activity is enriched in mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) and that ER-mitochondrial connectivity and MAM function are upregulated in AD. We now show that C99, in addition to its localization in endosomes, can also be found in MAM, where it is normally processed rapidly by c-secretase. In cell models of AD, however, the concentration of unprocessed C99 increases in MAM regions, resulting in elevated sphingolipid turnover and an altered lipid composition of both MAM and mitochondrial membranes. In turn, this change in mitochondrial membrane composition interferes with the proper assembly and activity of mitochondrial respiratory supercomplexes, thereby likely contributing to the bioenergetic defects characteristic of AD.We thank Drs. Orian Shirihai and Marc Liesa (UCLA) for assistance with the Seahorse measurements, Dr. Huaxi Xu (Sanford Burnham Institute) for the APP-DKO MEFs and Dr. Mark Mattson (NIH) for the PS1 knock-in mice, Drs. Arancio and Teich for the APP-KO mice tissues used in these studies, Dr. Hua Yang (Columbia University) for mouse husbandry, and Drs. Marc Tambini, Ira Tabas, and Serge Przedborski for helpful comments. This work was supported by the Fundacion Alfonso Martin Escudero (to M.P.); the Alzheimer's Drug Discovery Foundation, the Ellison Medical Foundation, the Muscular Dystrophy Association, the U.S. Department of Defense W911NF-12-1-9159 and W911F-15-1-0169), and the J. Willard and Alice S. Marriott Foundation (to E.A.S.); the U.S. National Institutes of Health (P01-HD080642 and P01-HD032062 to E.A.S.; NS071571 and HD071593 to M.F.M.; R01-NS056049 and P50-AG008702 to G.D.P.; 1S10OD016214-01A1 to G.S.P. and F.P.M, and K01-AG045335 to E.A.-G.), the Lucien Cote Early Investigator Award in Clinical Genetics from the Parkinson's Disease Foundation (PDF-CEI-1364 and PDF-CEI-1240) to C.G.-L., and National Defense Science and Engineering Graduate Fellowship (FA9550-11-C-0028) to R.R.A.S

Three-Dimensional Regulation of Radial Glial Functions by Lis1-Nde1 and Dystrophin Glycoprotein Complexes

Lis1-Nde1 integrates cerebral cortical neurogenesis with neuronal migration by stabilizing the basal-lateral surface of radial glial cells

Mutational Analysis of Photosystem I of Synechocystis sp. PCC 6803: The Role of Four Conserved Aromatic Residues in the j-helix of PsaB

Photosystem I is the light-driven plastocyanin-ferredoxin oxidoreductase in the photosynthetic electron transfer of cyanobacteria and plants. Two histidyl residues in the symmetric transmembrane helices A-j and B-j provide ligands for the P700 chlorophyll molecules of the reaction center of photosystem I. To determine the role of conserved aromatic residues adjacent to the histidyl molecule in the helix of B-j, we generated six site-directed mutants of the psaB gene in Synechocystis sp. PCC 6803. Three mutant strains with W645C, W643C/A644I and S641C/V642I substitutions could grow photoautotrophically and showed no obvious reduction in the photosystem I activity. Kinetics of P700 re-reduction by plastocyanin remained unaltered in these mutants. In contrast, the strains with H651C/L652M, F649C/G650I and F647C substitutions could not grow under photoautotrophic conditions because those mutants had low photosystem I activity, possibly due to low levels of proteins. A procedure to select spontaneous revertants from the mutants that are incapable to photoautotrophic growth resulted in three revertants that were used in this study. The molecular analysis of the spontaneous revertants suggested that an aromatic residue at F647 and a small residue at G650 may be necessary for maintaining the structural integrity of photosystem I. The (P700+ - P700) steady-state absorption difference spectrum of the revertant F647Y has a ∼5 nm narrower peak than the recovered wild-type, suggesting that additional hydroxyl group of this revertant may participate in the interaction with the special pair while the photosystem I complexes of the F649C/G650T and H651Q mutants closely resemble the wild-type spectrum. The results presented here demonstrate that the highly conserved residues W645, W643 and F649 are not critical for maintaining the integrity and in mediating electron transport from plastocyanin to photosystem I. Our data suggest that an aromatic residue is required at position of 647 for structural integrity and/or function of photosystem I

EEG ERP preregistration template

This preregistration template guides researchers who wish to preregister their EEG projects, more specifically studies investigating event-related potentials (ERPs) in the sensor space

The Structure of the EU Mediasphere

Background. A trend towards automation of scientific research has recently resulted in what has been termed “data-driven inquiry” in various disciplines, including physics and biology. The automation of many tasks has been identified as a possible future also for the humanities and the social sciences, particularly in those disciplines concerned with the analysis of text, due to the recent availability of millions of books and news articles in digital format. In the social sciences, the analysis of news media is done largely by hand and in a hypothesis-driven fashion: the scholar needs to formulate a very specific assumption about the patterns that might be in the data, and then set out to verify if they are present or not. Methodology/Principal Findings. In this study, we report what we think is the first large scale content-analysis of cross-linguistic text in the social sciences, by using various artificial intelligence techniques. We analyse 1.3 M news articles in 22 languages detecting a clear structure in the choice of stories covered by the various outlets. This is significantly affected by objective national, geographic, economic and cultural relations among outlets and countries, e.g., outlets from countries sharing strong economic ties are more likely to cover the same stories. We also show that the deviation from average content is significantly correlated with membership to the eurozone, as well as with the year of accession to the EU. Conclusions/Significance. While independently making a multitude of small editorial decisions, the leading media of the 27 EU countries, over a period of six months, shaped the contents of the EU mediasphere in a way that reflects its deep geographic, economic and cultural relations. Detecting these subtle signals in a statistically rigorous way would be out of the reach of traditional methods. This analysis demonstrates the power of the available methods for significant automation of media content analysis

A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome

Several genome-wide transcriptomics efforts have shown that a large percentage of the mammalian genome is transcribed into RNAs, however, only a small percentage (1–2%) of these RNAs is translated into proteins. Currently there is an intense interest in characterizing the function of the different classes of noncoding RNAs and their relevance to human disease. Using genomic approaches we discovered FMR4, a primate-specific noncoding RNA transcript (2.4 kb) that resides upstream and likely shares a bidirectional promoter with FMR1. FMR4 is a product of RNA polymerase II and has a similar half-life to FMR1. The CGG expansion in the 5′ UTR of FMR1 appears to affect transcription in both directions as we found FMR4, similar to FMR1, to be silenced in fragile X patients and up-regulated in premutation carriers. Knockdown of FMR4 by several siRNAs did not affect FMR1 expression, nor vice versa, suggesting that FMR4 is not a direct regulatory transcript for FMR1. However, FMR4 markedly affected human cell proliferation in vitro; siRNAs knockdown of FMR4 resulted in alterations in the cell cycle and increased apoptosis, while the overexpression of FMR4 caused an increase in cell proliferation. Collectively, our results demonstrate an antiapoptotic function of FMR4 and provide evidence that a well-studied genomic locus can show unexpected functional complexity. It cannot be excluded that altered FMR4 expression might contribute to aspects of the clinical presentation of fragile X syndrome and/or related disorders