Lactobacillus salivarius and L. gasseri down-regulate Aggregatibacter actinomycetemcomitans exotoxins expression

Beneficial microbes, such as lactobacilli establish a symbiosis with the host and confer health-associated effects, by limiting the growth of indigenous pathogens and challenging microbes introduced by altered foods. Nevertheless, there is scarce information on the effects of beneficial microbes on the virulence properties of bacterial species associated with oral diseases, such as periodontitis. Aggregatibacter actinomycetemcomitans is a Gram-negative species highly implicated in the etiology of localized aggressive periodontitis. The objective of this study was to investigate the effect of lactobacilli on the expression of the two major virulence factors of A. actinomycetemcomitans. Lactobacillus salivarius and L. gasseri were selected as beneficial species. The gene expressions of leukotoxin (LtxA) and cytolethal distending toxin (CdtB) by A. actinomycetemcomitans were analyzed in response to challenge by lactobacilli cell-free supernatants. Neither lactobacilli affected the growth, but strongly attenuated the expressions of both CdtB and LtxA in the two A. actinomycetemcomitans strains tested. This reduction of the expression of these two exotoxins was time-dependent. These fundamental findings may indicate that lactobacilli can reduce the virulence of putative opportunistic oral pathogens, and may provide insights to future therapeutic approaches for the respective diseases.     

Insights into the use of an unmanned aerial vehicle (UAV) to investigate the behavior of humpback whales (Megaptera novaeangliae) in Vava'u,Kingdom of Tonga

Vertical take-off and landing (VTOL) unmanned aerial vehicles (UAVs) are becoming invaluable data collection platforms for cetacean research. In particular, multi-rotors can be used to measure whales and investigate their behavior. Moreover, VTOL UAVs are increasingly accessible for recreational and commercial pilots, and close encounters with whales are widely documented. Unfortunately, quantitative assessments of potential disturbance for the targeted animals are not yet published and guidelines for responsible use of UAVs around cetaceans are still under development. We conducted VTOL UAV surveys on humpback whales in Vava'u, Kingdom of Tonga. Interestingly, whale behaviors such as socializing and nurturing were not detected by trained observers on board the research vessel, but were evident from the UAV. Nevertheless, no significant differences were detected in diving and swim parameters between absence and presence of UAV flying at 30 m altitude. These results suggest that VTOL UAVs can be a noninvasive tool to gather morphometric and behavioral data on baleen whales. However, further research is necessary to establish whether applications that require flight altitudes lower than 30 m and targeting different species may elicit behavioral responses.     

Efficient Universal Computing Architectures for Decoding Neural Activity

The ability to decode neural activity into meaningful control signals for prosthetic devices is critical to the development of clinically useful brain– machine interfaces (BMIs). Such systems require input from tens to hundreds of brain-implanted recording electrodes in order to deliver robust and accurate performance; in serving that primary function they should also minimize power dissipation in order to avoid damaging neural tissue; and they should transmit data wirelessly in order to minimize the risk of infection associated with chronic, transcutaneous implants. Electronic architectures for brain– machine interfaces must therefore minimize size and power consumption, while maximizing the ability to compress data to be transmitted over limited-bandwidth wireless channels. Here we present a system of extremely low computational complexity, designed for real-time decoding of neural signals, and suited for highly scalable implantable systems. Our programmable architecture is an explicit implementation of a universal computing machine emulating the dynamics of a network of integrate-and-fire neurons; it requires no arithmetic operations except for counting, and decodes neural signals using only computationally inexpensive logic operations. The simplicity of this architecture does not compromise its ability to compress raw neural data by factors greater than . We describe a set of decoding algorithms based on this computational architecture, one designed to operate within an implanted system, minimizing its power consumption and data transmission bandwidth; and a complementary set of algorithms for learning, programming the decoder, and postprocessing the decoded output, designed to operate in an external, nonimplanted unit. The implementation of the implantable portion is estimated to require fewer than 5000 operations per second. A proof-of-concept, 32-channel field-programmable gate array (FPGA) implementation of this portion is consequently energy efficient. We validate the performance of our overall system by decoding electrophysiologic data from a behaving rodent.     

Contribution of Genome-Wide Association Studies to Scientific Research: A Pragmatic Approach to Evaluate Their Impact

The factual value of genome-wide association studies (GWAS) for the understanding of multifactorial diseases is a matter of intense debate. Practical consequences for the development of more effective therapies do not seem to be around the corner. Here we propose a pragmatic and objective evaluation of how much new biology is arising from these studies, with particular attention to the information that can help prioritize therapeutic targets. We chose multiple sclerosis (MS) as a paradigm disease and assumed that, in pre-GWAS candidate-gene studies, the knowledge behind the choice of each gene reflected the understanding of the disease prior to the advent of GWAS. Importantly, this knowledge was based mainly on non-genetic, phenotypic grounds. We performed single-gene and pathway-oriented comparisons of old and new knowledge in MS by confronting an unbiased list of candidate genes in pre-GWAS association studies with those genes exceeding the genome-wide significance threshold in GWAS published from 2007 on. At the single gene level, the majority (94 out of 125) of GWAS-discovered variants had never been contemplated as plausible candidates in pre-GWAS association studies. The 31 genes that were present in both pre- and post-GWAS lists may be of particular interest in that they represent disease-associated variants whose pathogenetic relevance is supported at the phenotypic level (i.e. the phenotypic information that steered their selection as candidate genes in pre-GWAS association studies). As such they represent attractive therapeutic targets. Interestingly, our analysis shows that some of these variants are targets of pharmacologically active compounds, including drugs that are already registered for human use. Compared with the above single-gene analysis, at the pathway level GWAS results appear more coherent with previous knowledge, reinforcing some of the current views on MS pathogenesis and related therapeutic research. This study presents a pragmatic approach that helps interpret and exploit GWAS knowledge.     

MECP2 Duplication Syndrome: Evidence of Enhanced Oxidative Stress. A Comparison with Rett Syndrome

Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) are neurodevelopmental disorders caused by alterations in the methyl-CpG binding protein 2 (MECP2) gene expression. A relationship between MECP2 loss-of-function mutations and oxidative stress has been previously documented in RTT patients and murine models. To date, no data on oxidative stress have been reported for the MECP2 gain-of-function mutations in patients with MDS. In the present work, the pro-oxidant status and oxidative fatty acid damage in MDS was investigated (subjects n = 6) and compared to RTT (subjects n = 24) and healthy condition (subjects n = 12). Patients with MECP2 gain-of-function mutations showed increased oxidative stress marker levels (plasma non-protein bound iron, intraerythrocyte non-protein bound iron, F₂-isoprostanes, and F₄-neuroprostanes), as compared to healthy controls (P ≤ 0.05). Such increases were similar to those observed in RTT patients except for higher plasma F₂-isoprostanes levels (P < 0.0196). Moreover, plasma levels of F₂-isoprostanes were significantly correlated (P = 0.0098) with the size of the amplified region. The present work shows unique data in patients affected by MDS. For the first time MECP2 gain-of-function mutations are indicated to be linked to an oxidative damage and related clinical symptoms overlapping with those of MECP2 loss-of-function mutations. A finely tuned balance of MECP2 expression appears to be critical to oxidative stress homeostasis, thus shedding light on the relevance of the redox balance in the central nervous system integrity.     

Sampling errors in anchovy egg abundance estimates using the PAIROVET net

A replicate haul experiment was carried out using the verticallytowed PAIROVET net in an area of high abundance of anchovy eggsin the Bay of Biscay. The main aim of the experiment was tocompare the performance of ships of different size working inthe same area. In addition, we tested the performance of thePAIROVET net and the deployment methodology used to sample anchovyeggs for biomass assessment purposes. We concluded that underthe experimental conditions experienced in this cruise, differentships yield similar performances of the vertically towed PAIROVETnet if the methodology is kept similar. The ANOVA suggests thatthe systematic central sampling (SCS) scheme currently in usefor the Bay of Biscay anchovy biomass estimations (one stationout at 3 miles) adequately represents the surrounding area alongthe transect line. The among-station component of variance withinthe unit sampling area of the current SCS turned out to be comparableand, in some cases, smaller than the within-station variance.Consequently, the spatial design of the SCS adopted during routinesurveys appears to be a reliable strategy for sampling anchovyeggs in areas of high egg abundance, as in this experiment.In addition, it ensures fairly independent data units. In thearea of the experiment, the most disperse egg stages (like 2-and 3-day-old eggs) show a larger within-station component ofvariance than the spatial component of variance within the rectanglesof the current SCS. This suggests that for these stages, thesampling can still be improved cheaply by increasing the precisionof egg abundance estimates per station with larger sample sizes,without changing the spatial sampling scheme or the number ofstations. However, the benefits of this strategy will hardlyaffect the precision of the 1-day-old egg estimates becauseof their patchy distribution.     

Steroids interfere with human carbonic anhydrase activity by using alternative binding mechanisms

Bile acids have been shown to inhibit human (h) carbonic anhydrases (CA, EC 4.2.1.1) along the gastrointestinal tract, including hCA II. The elucidation of the hormonal inhibition mechanism of the bile acid cholate to hCA II was provided in 2014 by X-ray crystallography. Herein, we extend the inhibition study to a wealth of steroids against four relevant hCA isoforms. Steroids displaying pendants and functional groups of the carboxylate, phenolic or sulfonate types appended at the tetracyclic ring were shown to inhibit the cytosolic CA II and the tumor-associated, transmembrane CA IX in a medium micromolar range (38.9–89.9?µM). Docking studies displayed the different chemotypes CA inhibition mechanisms. Molecular dynamics (MD) gave insights on the stability over time of hyocholic acid binding to CA II.