Engineering strategies to decode and enhance the genomes of coral symbionts

© 2017 Levin, Voolstra, Agrawal, Steinberg, Suggett and van Oppen. Elevated sea surface temperatures from a severe and prolonged El Niño event (2014-2016) fueled by climate change have resulted in mass coral bleaching (loss of dinoflagellate photosymbionts, Symbiodinium spp., from coral tissues) and subsequent coral mortality, devastating reefs worldwide. Genetic variation within and between Symbiodinium species strongly influences the bleaching tolerance of corals, thus recent papers have called for genetic engineering of Symbiodinium to elucidate the genetic basis of bleaching-relevant Symbiodinium traits. However, while Symbiodinium has been intensively studied for over 50 years, genetic transformation of Symbiodinium has seen little success likely due to the large evolutionary divergence between Symbiodinium and other model eukaryotes rendering standard transformation systems incompatible. Here, we integrate the growing wealth of Symbiodinium next-generation sequencing data to design tailored genetic engineering strategies. Specifically, we develop a testable expression construct model that incorporates endogenous Symbiodinium promoters, terminators, and genes of interest, as well as an internal ribosomal entry site from a Symbiodinium virus. Furthermore, we assess the potential for CRISPR/Cas9 genome editing through new analyses of the three currently available Symbiodinium genomes. Finally, we discuss how genetic engineering could be applied to enhance the stress tolerance of Symbiodinium, and in turn, coral reefs

Quantum walks can find a marked element on any graph

We solve an open problem by constructing quantum walks that not only detect but also find marked vertices in a graph. In the case when the marked set $M$ consists of a single vertex, the number of steps of the quantum walk is quadratically smaller than the classical hitting time $HT(P,M)$ of any reversible random walk $P$ on the graph. In the case of multiple marked elements, the number of steps is given in terms of a related quantity $HT^+(\mathit{P,M})$ which we call extended hitting time. Our approach is new, simpler and more general than previous ones. We introduce a notion of interpolation between the random walk $P$ and the absorbing walk $P'$, whose marked states are absorbing. Then our quantum walk is simply the quantum analogue of this interpolation. Contrary to previous approaches, our results remain valid when the random walk $P$ is not state-transitive. We also provide algorithms in the cases when only approximations or bounds on parameters $p_M$ (the probability of picking a marked vertex from the stationary distribution) and $HT^+(\mathit{P,M})$ are known.Comment: 50 page

Mindfulness-based stress reduction in Parkinson’s disease: a systematic review

Background: Mindfulness based stress reduction (MBSR) is increasingly being used to improve outcomes such as stress and depression in a range of long-term conditions (LTCs). While systematic reviews on MBSR have taken place for a number of conditions there remains limited information on its impact on individuals with Parkinson’s disease (PD). Methods: Medline, Central, Embase, Amed, CINAHAL were searched in March 2016. These databases were searched using a combination of MeSH subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed based on questions from the Cochrane Collaboration risk of bias tool. Results: Two interventions and three papers with a total of 66 participants were included. The interventions were undertaken in Belgium (n = 27) and the USA (n = 39). One study reported significantly increased grey matter density (GMD) in the brains of the MBSR group compared to the usual care group. Significant improvements were reported in one study for a number of outcomes including PD outcomes, depression, mindfulness, and quality of life indicators. Only one intervention was of reasonable quality and both interventions failed to control for potential confounders in the analysis. Adverse events and reasons for drop-outs were not reported. There was also no reporting on the costs/benefits of the intervention or how they affected health service utilisation. Conclusion: This systematic review found limited and inconclusive evidence of the effectiveness of MBSR for PD patients. Both of the included interventions claimed positive effects for PD patients but significant outcomes were often contradicted by other results. Further trials with larger sample sizes, control groups and longer follow-ups are needed before the evidence for MBSR in PD can be conclusively judged

High Energy Bounds on Soft N=4 SYM Amplitudes from AdS/CFT

Using the AdS/CFT correspondence, we study the high-energy behavior of colorless dipole elastic scattering amplitudes in N=4 SYM gauge theory through the Wilson loop correlator formalism and Euclidean to Minkowskian analytic continuation. The purely elastic behavior obtained at large impact-parameter L, through duality from disconnected AdS_5 minimal surfaces beyond the Gross-Ooguri transition point, is combined with unitarity and analyticity constraints in the central region. In this way we obtain an absolute bound on the high-energy behavior of the forward scattering amplitude due to the graviton interaction between minimal surfaces in the bulk. The dominant "Pomeron" intercept is bounded by alpha less than or equal to 11/7 using the AdS/CFT constraint of a weak gravitational field in the bulk. Assuming the elastic eikonal approximation in a larger impact-parameter range gives alpha between 4/3 and 11/7. The actual intercept becomes 4/3 if one assumes the elastic eikonal approximation within its maximally allowed range L larger than exp{Y/3}, where Y is the total rapidity. Subleading AdS/CFT contributions at large impact-parameter due to the other d=10 supergravity fields are obtained. A divergence in the real part of the tachyonic KK scalar is cured by analyticity but signals the need for a theoretical completion of the AdS/CFT scheme.Comment: 25 pages, 3 eps figure

Reggeon exchange from gauge/gravity duality

We perform the analysis of quark-antiquark Reggeon exchange in meson-meson scattering, in the framework of the gauge/gravity correspondence in a confining background. On the gauge theory side, Reggeon exchange is described as quark-antiquark exchange in the t channel between fast projectiles. The corresponding amplitude is represented in terms of Wilson loops running along the trajectories of the constituent quarks and antiquarks. The paths of the exchanged fermions are integrated over, while the "spectator" fermions are dealt with in an eikonal approximation. On the gravity side, we follow a previously proposed approach, and we evaluate the Wilson-loop expectation value by making use of gauge/gravity duality for a generic confining gauge theory. The amplitude is obtained in a saddle-point approximation through the determination near the confining horizon of a Euclidean "minimal surface with floating boundaries", i.e., by fixing the trajectories of the exchanged quark and antiquark by means of a minimisation procedure, which involves both area and length terms. After discussing, as a warm-up exercise, a simpler problem on a plane involving a soap film with floating boundaries, we solve the variational problem relevant to Reggeon exchange, in which the basic geometry is that of a helicoid. A compact expression for the Reggeon-exchange amplitude, including the effects of a small fermion mass, is then obtained through analytic continuation from Euclidean to Minkowski space-time. We find in particular a linear Regge trajectory, corresponding to a Regge-pole singularity supplemented by a logarithmic cut induced by the non-zero quark mass. The analytic continuation leads also to companion contributions, corresponding to the convolution of the same Reggeon-exchange amplitude with multiple elastic rescattering interactions between the colliding mesons.Comment: 60+1 pages, 14 figure

Otodental syndrome

The otodental syndrome also named otodental dysplasia, is characterised by a striking dental phenotype known as globodontia, associated with sensorineural high frequency hearing loss and eye coloboma. Globodontia occurs in both primary and permanent dentition, affecting canine and molar teeth (i.e. enlarged bulbous malformed posterior teeth with almost no discernable cusps or grooves). The condition appears to be inherited in an autosomal dominant mode, although sporadic cases have been reported. It is a rare disease, a few families have been described in the literature. In the British family, the locus for oculo-oto-dental syndrome was mapped to 20q13.1 within a 12-cM critical chromosomal region. Dental management is complex, interdisciplinary and will include regular follow up, scheduled teeth extraction and orthodontic treatment. Hearing checks and, if necessary, hearing aids are mandatory, as well as eye examination and ad hoc treatment if necessary

Comparative Developmental Neurotoxicity of Organophosphate Insecticides: Effects on Brain Development Are Separable from Systemic Toxicity

A comparative approach to the differences between systemic toxicity and developmental neurotoxicity of organophosphates is critical to determine the degree to which multiple mechanisms of toxicity carry across different members of this class of insecticides. We contrasted neuritic outgrowth and cholinergic synaptic development in neonatal rats given different organophosphates (chlorpyrifos, diazinon, parathion) at doses spanning the threshold for impaired growth and viability. Animals were treated daily on postnatal days 1–4 by subcutaneous injection so as to bypass differences in first-pass activation to the oxon or catabolism to inactive products. Evaluations occurred on day 5. Parathion (maximum tolerated dose, 0.1 mg/kg) was far more systemically toxic than was chlorpyrifos or diazinon (maximum tolerated dose, 1–5 mg/kg). Below the maximum tolerated dose, diazinon impaired neuritic outgrowth in the forebrain and brainstem, evidenced by a deficit in the ratio of membrane protein to total protein. Diazinon also decreased choline acetyltransferase activity, a cholinergic neuronal marker, whereas it did not affect hemicholinium-3 binding to the presynaptic choline transporter, an index of cholinergic neuronal activity. There was no m(2)-muscarinic acetylcholine receptor down-regulation, as would have occurred with chronic cholinergic hyper-stimulation. The same pattern was found previously for chlorpyrifos. In contrast, parathion did not elicit any of these changes at its maximum tolerated dose. These results indicate a complete dichotomy between the systemic toxicity of organophosphates and their propensity to elicit developmental neurotoxicity. For parathion, the threshold for lethality lies below that necessary for adverse effects on brain development, whereas the opposite is true for chlorpyrifos and diazinon

Comparison and relative utility of inequality measurements: as applied to Scotland’s child dental health

This study compared and assessed the utility of tests of inequality on a series of very large population caries datasets. National cross-sectional caries datasets for Scotland’s 5-year-olds in 1993/94 (n = 5,078); 1995/96 (n = 6,240); 1997/98 (n = 6,584); 1999/00 (n = 6,781); 2002/03 (n = 9,747); 2003/04 (n = 10,956); 2005/06 (n = 10,945) and 2007/08 (n = 12,067) were obtained. Outcomes were based on the d3mft metric (i.e. the number of decayed, missing and filled teeth). An area-based deprivation category (DepCat) measured the subjects’ socioeconomic status (SES). Simple absolute and relative inequality, Odds Ratios and the Significant Caries Index (SIC) as advocated by the World Health Organization were calculated. The measures of complex inequality applied to data were: the Slope Index of Inequality (absolute) and a variety of relative inequality tests i.e. Gini coefficient; Relative Index of Inequality; concentration curve; Koolman and Doorslaer’s transformed Concentration Index; Receiver Operator Curve and Population Attributable Risk (PAR). Additional tests used were plots of SIC deciles (SIC10) and a Scottish Caries Inequality Metric (SCIM10). Over the period, mean d3mft improved from 3.1(95%CI 3.0–3.2) to 1.9(95%CI 1.8–1.9) and d3mft = 0% from 41.1(95%CI 39.8–42.3) to 58.3(95%CI 57.8–59.7). Absolute simple and complex inequality decreased. Relative simple and complex inequality remained comparatively stable. Our results support the use of the SII and RII to measure complex absolute and relative SES inequalities alongside additional tests of complex relative inequality such as PAR and Koolman and Doorslaer’s transformed CI. The latter two have clear interpretations which may influence policy makers. Specialised dental metrics (i.e. SIC, SIC10 and SCIM10) permit the exploration of other important inequalities not determined by SES, and could be applied to many other types of disease where ranking of morbidity is possible e.g. obesity. More generally, the approaches described may be applied to study patterns of health inequality affecting worldwide populations