No-scale D=5 supergravity from Scherk-Schwarz reduction of D=6 theories

We perform a generalized dimensional reduction of six dimensional supergravity theories to five dimensions. We consider the minimal $(2,0)$ and the maximal $(4,4)$ theories. In each case the reduction allows us to obtain gauged supergravities of no-scale type in dimension five with gauge groups that escape previous classifications. In the minimal case, the geometric data of the reduced theory correspond to particular cases of the D=5 real special geometry. In the maximal case we find a four parameter solution which allows partial breaking of supersymmetry.Comment: AMS-LaTeX 16 pages. A reference added, some minor changes performe

Detecting the effects of deep-seabed nodule mining: simulations using Megafaunal Data From the Clarion-Clipperton Zone

The International Seabed Authority (ISA) is in the process of preparing exploitation regulations for deep-seabed mining (DSM). DSM has the potential to disturb the seabed over wide areas, yet there is little information on the ecological consequences, both at the site of mining and surrounding areas where disturbance such as sediment smothering could occur. Of critical regulatory concern is whether the impacts cause “serious harm” to the environment. Using metazoan megafaunal data from the Clarion-Clipperton Zone (northern equatorial Pacific), we simulate a range of disturbances from very low to severe, to determine the effect on community-level metrics. Two kinds of stressors were simulated: one that impacts organisms based on their affinity to nodules, and another that applies spatially stochastic stress to all organisms. These simulations are then assessed using power analysis to determine the amount of sampling required to distinguish the disturbances. This analysis is limited to modelling lethal impacts on megafauna. It provides a first indication of the effect sizes and ecological nature of mining impacts that might be expected across a broader range of taxa. To detect our simulated “tipping point,” power analyses suggest impact monitoring samples should each have at least 500–750 individual megafauna; and at least five such samples, as well as control samples should be assessed. In the region studied, this translates to approximately 1500–2300 m2 seabed per impact monitoring sample, i.e., 7500–11,500 m2 in total for a given location and/or habitat. Detecting less severe disturbances requires more sampling. The numerical density of individuals and Pielou’s evenness of communities appear most sensitive to simulated disturbances and may provide suitable “early warning” metrics for monitoring. To determine the sampling details for detecting the desired threshold(s) for harm, statistical effect sizes will need to be determined and validated. The determination of what constitutes serious harm is a legal question that will need to consider socially acceptable levels of long-term harm to deep-sea life. Monitoring details, data, and results including power analyses should be made fully available, to facilitate independent review and informed policy discussions

Identification of vaginal microbiome associated with IVF pregnancy

The factors that cause a preterm birth (PTB) are not completely understood up to date. Moreover, PTB is more common in pregnancies achieved by in-vitro fertilization (IVF) than in spontaneous pregnancies. Our aim was to compare the composition of vaginal microbiome at 12 weeks of gestation between women who conceived naturally or through IVF in order to study whether IVF PTB-risk could be related to vaginal microbiome composition. We performed an observational, prospective and multicentre study among two public hospitals and a fertility private clinic in Spain. Vaginal swabs from 64 pregnant women at 12 weeks of gestation were collected to analyse the microbiome composition by sequencing the V3–V4 region of the 16S rRNA. Our results showed that the vaginal microbiome signature at 12 weeks of pregnancy was different from women who conceived naturally or through IVF. The beta diversity and the genus composition were different between both cohorts. Gardnerella, Neisseria, Prevotella, and Staphylococcus genus were enriched genus in the vaginal microbiome from the IVF group, allowing us to create a balance model to predict both cohorts. Moreover, at species level the L. iners abundance was higher and L. gasseri was lower in the IVF group. As a conclusion, our findings were consistent with a proposed framework in which IVF pregnancy are related to risk for preterm birth (PTB) suggesting vaginal microbiome could be the reason to the relation between IVF pregnancy and risk for PTB

Ecology of a polymetallic nodule occurrence gradient: Implications for deep-sea mining

Abyssal polymetallic nodule fields constitute an unusual deep‐sea habitat. The mix of soft sediment and the hard substratum provided by nodules increases the complexity of these environments. Hard substrata typically support a very distinct fauna to that of seabed sediments, and its presence can play a major role in the structuring of benthic assemblages. We assessed the influence of seafloor nodule cover on the megabenthos of a marine conservation area (area of particular environmental interest 6) in the Clarion Clipperton Zone (3950–4250 m water depth) using extensive photographic surveys from an autonomous underwater vehicle. Variations in nodule cover (1–20%) appeared to exert statistically significant differences in faunal standing stocks, some biological diversity attributes, faunal composition, functional group composition, and the distribution of individual species. The standing stock of both the metazoan fauna and the giant protists (xenophyophores) doubled with a very modest initial increase in nodule cover (from 1% to 3%). Perhaps contrary to expectation, we detected little if any substantive variation in biological diversity along the nodule cover gradient. Faunal composition varied continuously along the nodule cover gradient. We discuss these results in the context of potential seabed‐mining operations and the associated sustainable management and conservation plans. We note in particular that successful conservation actions will likely require the preservation of areas comprising the full range of nodule cover and not just the low cover areas that are least attractive to mining

The use of compression stockings during a marathon competition to reduce exercise-induced muscle damage: are they really useful?

OBJECTIVES: To examine the efficacy of wearing compression stockings to prevent muscle damage and to maintain running performance during a marathon competition. BACKGROUND: Exercise-induced muscle damage has been identified as one of the main causes of the progressive decrease in running and muscular performance found during marathon races. METHODS: Thirty-four experienced runners were pair-matched for age, anthropometric data, and best race time in the marathon, and randomly assigned to a control group (n = 17) of runners who wore conventional socks or to a group of runners who wore foot-to-knee graduated compression stockings (n = 17). Before and after the race, a sample of venous blood was obtained, and jump height and leg muscle power were measured during a countermovement jump. Serum myoglobin and creatine kinase concentrations were determined as blood markers of muscle fiber damage

Neurogenesis Drives Stimulus Decorrelation in a Model of the Olfactory Bulb

The reshaping and decorrelation of similar activity patterns by neuronal networks can enhance their discriminability, storage, and retrieval. How can such networks learn to decorrelate new complex patterns, as they arise in the olfactory system? Using a computational network model for the dominant neural populations of the olfactory bulb we show that fundamental aspects of the adult neurogenesis observed in the olfactory bulb -- the persistent addition of new inhibitory granule cells to the network, their activity-dependent survival, and the reciprocal character of their synapses with the principal mitral cells -- are sufficient to restructure the network and to alter its encoding of odor stimuli adaptively so as to reduce the correlations between the bulbar representations of similar stimuli. The decorrelation is quite robust with respect to various types of perturbations of the reciprocity. The model parsimoniously captures the experimentally observed role of neurogenesis in perceptual learning and the enhanced response of young granule cells to novel stimuli. Moreover, it makes specific predictions for the type of odor enrichment that should be effective in enhancing the ability of animals to discriminate similar odor mixtures

Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+](i)) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.Fundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e Tecnologiainfo:eu-repo/semantics/publishedVersio

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Complex Odor from Plants under Attack: Herbivore's Enemies React to the Whole, Not Its Parts

Background: Insect herbivory induces plant odors that attract herbivores ’ natural enemies. Assuming this attraction emerges from individual compounds, genetic control over odor emission of crops may provide a rationale for manipulating the distribution of predators used for pest control. However, studies on odor perception in vertebrates and invertebrates suggest that olfactory information processing of mixtures results in odor percepts that are a synthetic whole and not a set of components that could function as recognizable individual attractants. Here, we ask if predators respond to herbivoreinduced attractants in odor mixtures or to odor mixture as a whole. Methodology/Principal Findings: We studied a system consisting of Lima bean, the herbivorous mite Tetranychus urticae and the predatory mite Phytoseiulus persimilis. We found that four herbivore-induced bean volatiles are not attractive in pure form while a fifth, methyl salicylate (MeSA), is. Several reduced mixtures deficient in one component compared to the full spider-mite induced blend were not attractive despite the presence of MeSA indicating that the predators cannot detect this component in these odor mixtures. A mixture of all five HIPV is most attractive, when offered together with the noninduced odor of Lima bean. Odors that elicit no response in their pure form were essential components of the attractive mixture. Conclusions/Significance: We conclude that the predatory mites perceive odors as a synthetic whole and that th

Selective Gene Expression by Postnatal Electroporation during Olfactory Interneuron Neurogenesis

Neurogenesis persists in the olfactory system throughout life. The mechanisms of how new neurons are generated, how they integrate into circuits, and their role in coding remain mysteries. Here we report a technique that will greatly facilitate research into these questions. We found that electroporation can be used to robustly and selectively label progenitors in the Subventicular Zone. The approach was performed postnatally, without surgery, and with near 100% success rates. Labeling was found in all classes of interneurons in the olfactory bulb, persisted to adulthood and had no adverse effects. The broad utility of electroporation was demonstrated by encoding a calcium sensor and markers of intracellular organelles. The approach was found to be effective in wildtype and transgenic mice as well as rats. Given its versatility, robustness, and both time and cost effectiveness, this method offers a powerful new way to use genetic manipulation to understand adult neurogenesis