Patient Awareness and Approval for an Opt-Out Genomic Biorepository

Aim: In this study, we sought to assess patient awareness and perceptions of an opt-out biorepository. Materials & methods: We conducted exit interviews with adult patients and parents of pediatric patients having their blood drawn as part of their clinical care at Vanderbilt University Medical Center (TN, USA). Results: 32.9% of all patients and parents of pediatric patients report having heard of the opt-out biorepository, while 92.4% approve of this research effort based on a brief description. Awareness that leftover blood could be used for research increased among adult patients during the study period, from 34.3 to 50.0%. Conclusion: These findings will inform ongoing assessments of the suitability of opt-out and opt-in methods as alternatives to written informed consent for inclusion in a biorepository

Sustainability appraisal: Jack of all trades, master of none?

Sustainable development is a commonly quoted goal for decision making and supports a large number of other discourses. Sustainability appraisal has a stated goal of supporting decision making for sustainable development. We suggest that the inherent flexibility of sustainability appraisal facilitates outcomes that often do not adhere to the three goals enshrined in most definitions of sustainable development: economic growth, environmental protection and enhancement, and the wellbeing of the human population. Current practice is for sustainable development to be disenfranchised through the interpretation of sustainability, whereby the best alternative is good enough even when unsustainable. Practitioners must carefully and transparently review the frameworks applied during sustainability appraisal to ensure that outcomes will meet the three goals, rather than focusing on a discourse that emphasises one or more goals at the expense of the other(s)

Structural divergence creates new functional features in alphavirus genomes

Alphaviruses are mosquito-borne pathogens that cause human diseases ranging from debilitating arthritis to lethal encephalitis. Studies with Sindbis virus (SINV), which causes fever, rash, and arthralgia in humans, and Venezuelan equine encephalitis virus (VEEV), which causes encephalitis, have identified RNA structural elements that play key roles in replication and pathogenesis. However, a complete genomic structural profile has not been established for these viruses. We used the structural probing technique SHAPE-MaP to identify structured elements within the SINV and VEEV genomes. Our SHAPE-directed structural models recapitulate known RNA structures, while also identifying novel structural elements, including a new functional element in the nsP1 region of SINV whose disruption causes a defect in infectivity. Although RNA structural elements are important for multiple aspects of alphavirus biology, we found the majority of RNA structures were not conserved between SINV and VEEV. Our data suggest that alphavirus RNA genomes are highly divergent structurally despite similar genomic architecture and sequence conservation; still, RNA structural elements are critical to the viral life cycle. These findings reframe traditional assumptions about RNA structure and evolution: rather than structures being conserved, alphaviruses frequently evolve new structures that may shape interactions with host immune systems or co-evolve with viral proteins

Disruption of the Opal Stop Codon Attenuates Chikungunya Virus-Induced Arthritis and Pathology

ABSTRACT Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for several significant outbreaks of debilitating acute and chronic arthritis and arthralgia over the past decade. These include a recent outbreak in the Caribbean islands and the Americas that caused more than 1 million cases of viral arthralgia. Despite the major impact of CHIKV on global health, viral determinants that promote CHIKV-induced disease are incompletely understood. Most CHIKV strains contain a conserved opal stop codon at the end of the viral nsP3 gene. However, CHIKV strains that encode an arginine codon in place of the opal stop codon have been described, and deep-sequencing analysis of a CHIKV isolate from the Caribbean identified both arginine and opal variants within this strain. Therefore, we hypothesized that the introduction of the arginine mutation in place of the opal termination codon may influence CHIKV virulence. We tested this by introducing the arginine mutation into a well-characterized infectious clone of a CHIKV strain from Sri Lanka and designated this virus Opal524R. This mutation did not impair viral replication kinetics in vitro or in vivo . Despite this, the Opal524R virus induced significantly less swelling, inflammation, and damage within the feet and ankles of infected mice. Further, we observed delayed induction of proinflammatory cytokines and chemokines, as well as reduced CD4 + T cell and NK cell recruitment compared to those in the parental strain. Therefore, the opal termination codon plays an important role in CHIKV pathogenesis, independently of effects on viral replication. IMPORTANCE Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes significant outbreaks of viral arthralgia. Studies with CHIKV and other alphaviruses demonstrated that the opal termination codon within nsP3 is highly conserved. However, some strains of CHIKV and other alphaviruses contain mutations in the opal termination codon. These mutations alter the virulence of related alphaviruses in mammalian and mosquito hosts. Here, we report that a clinical isolate of a CHIKV strain from the recent outbreak in the Caribbean islands contains a mixture of viruses encoding either the opal termination codon or an arginine mutation. Mutating the opal stop codon to an arginine residue attenuates CHIKV-induced disease in a mouse model. Compared to infection with the opal-containing parental virus, infection with the arginine mutant causes limited swelling and inflammation, as well as dampened recruitment of immune mediators of pathology, including CD4 + T cells and NK cells. We propose that the opal termination codon plays an essential role in the induction of severe CHIKV disease

Highly conserved gene order and numerous novel repetitive elements in genomic regions linked to wing pattern variation in Heliconius butterflies

Background: With over 20 parapatric races differing in their warningly colored wing patterns, the butterfly Heliconius erato provides a fascinating example of an adaptive radiation. Together with matching races of its co-mimic Heliconius melpomene, H. erato also represents a textbook case of Müllerian mimicry, a phenomenon where common warning signals are shared amongst noxious organisms. It is of great interest to identify the specific genes that control the mimetic wing patterns of H. erato and H. melpomene. To this end we have undertaken comparative mapping and targeted genomic sequencing in both species. This paper reports on a comparative analysis of genomic sequences linked to color pattern mimicry genes in Heliconius. Results: Scoring AFLP polymorphisms in H. erato broods allowed us to survey loci at approximately 362 kb intervals across the genome. With this strategy we were able to identify markers tightly linked to two color pattern genes: D and Cr, which were then used to screen H. erato BAC libraries in order to identify clones for sequencing. Gene density across 600 kb of BAC sequences appeared relatively low, although the number of predicted open reading frames was typical for an insect. We focused analyses on the D- and Cr-linked H. erato BAC sequences and on the Yb-linked H. melpomene BAC sequence. A comparative analysis between homologous regions of H. erato (Cr-linked BAC) and H. melpomene (Yb-linked BAC) revealed high levels of sequence conservation and microsynteny between the two species. We found that repeated elements constitute 26% and 20% of BAC sequences from H. erato and H. melpomene respectively. The majority of these repetitive sequences appear to be novel, as they showed no significant similarity to any other available insect sequences. We also observed signs of fine scale conservation of gene order between Heliconius and the moth Bombyx mori, suggesting that lepidopteran genome architecture may be conserved over very long evolutionary time scales. Conclusion: Here we have demonstrated the tractability of progressing from a genetic linkage map to genomic sequence data in Heliconius butterflies. We have also shown that fine-scale gene order is highly conserved between distantly related Heliconius species, and also between Heliconius and B. mori. Together, these findings suggest that genome structure in macrolepidoptera might be very conserved, and show that mapping and positional cloning efforts in different lepidopteran species can be reciprocally informative

<i>Trypanosoma brucei rhodesiense</i> transmitted by a single tsetse fly bite in vervet monkeys as a model of human African trypanosomiasis

Sleeping sickness is caused by a species of trypanosome blood parasite that is transmitted by tsetse flies. To understand better how infection with this parasite leads to disease, we provide here the most detailed description yet of the course of infection and disease onset in vervet monkeys. One infected tsetse fly was allowed to feed on each host individual, and in all cases infections were successful. The characteristics of infection and disease were similar in all hosts, but the rate of progression varied considerably. Parasites were first detected in the blood 4-10 days after infection, showing that migration of parasites from the site of fly bite was very rapid. Anaemia was a key feature of disease, with a reduction in the numbers and average size of red blood cells and associated decline in numbers of platelets and white blood cells. One to six weeks after infection, parasites were observed in the cerebrospinal fluid (CSF), indicating that they had moved from the blood into the brain; this was associated with a white cell infiltration. This study shows that fly-transmitted infection in vervets accurately mimics human disease and provides a robust model to understand better how sleeping sickness develops

Decadal changes of the Western Arabian sea ecosystem

Historical data from oceanographic expeditions and remotely sensed data on outgoing longwave radiation, temperature, wind speed and ocean color in the western Arabian Sea (1950–2010) were used to investigate decadal trends in the physical and biochemical properties of the upper 300 m. 72 % of the 29,043 vertical profiles retrieved originated from USA and UK expeditions. Increasing outgoing longwave radiation, surface air temperatures and sea surface temperature were identified on decadal timescales. These were well correlated with decreasing wind speeds associated with a reduced Siberian High atmospheric anomaly. Shoaling of the oxycline and nitracline was observed as well as acidification of the upper 300 m. These physical and chemical changes were accompanied by declining chlorophyll-a concentrations, vertical macrofaunal habitat compression, declining sardine landings and an increase of fish kill incidents along the Omani coast

The fundamental constants and their variation: observational status and theoretical motivations

This article describes the various experimental bounds on the variation of the fundamental constants of nature. After a discussion on the role of fundamental constants, of their definition and link with metrology, the various constraints on the variation of the fine structure constant, the gravitational, weak and strong interactions couplings and the electron to proton mass ratio are reviewed. This review aims (1) to provide the basics of each measurement, (2) to show as clearly as possible why it constrains a given constant and (3) to point out the underlying hypotheses. Such an investigation is of importance to compare the different results, particularly in view of understanding the recent claims of the detections of a variation of the fine structure constant and of the electron to proton mass ratio in quasar absorption spectra. The theoretical models leading to the prediction of such variation are also reviewed, including Kaluza-Klein theories, string theories and other alternative theories and cosmological implications of these results are discussed. The links with the tests of general relativity are emphasized.Comment: 56 pages, l7 figures, submitted to Rev. Mod. Phy

Visual cues given by humans are not sufficient for Asian elephants (Elephas maximus) to find hidden food.

Recent research suggests that domesticated species--due to artificial selection by humans for specific, preferred behavioral traits--are better than wild animals at responding to visual cues given by humans about the location of hidden food. \Although this seems to be supported by studies on a range of domesticated (including dogs, goats and horses) and wild (including wolves and chimpanzees) animals, there is also evidence that exposure to humans positively influences the ability of both wild and domesticated animals to follow these same cues. Here, we test the performance of Asian elephants (Elephas maximus) on an object choice task that provides them with visual-only cues given by humans about the location of hidden food. Captive elephants are interesting candidates for investigating how both domestication and human exposure may impact cue-following as they represent a non-domesticated species with almost constant human interaction. As a group, the elephants (n = 7) in our study were unable to follow pointing, body orientation or a combination of both as honest signals of food location. They were, however, able to follow vocal commands with which they were already familiar in a novel context, suggesting the elephants are able to follow cues if they are sufficiently salient. Although the elephants' inability to follow the visual cues provides partial support for the domestication hypothesis, an alternative explanation is that elephants may rely more heavily on other sensory modalities, specifically olfaction and audition. Further research will be needed to rule out this alternative explanation