XperimentR: painless annotation of a biological experiment for the laboratory scientist

<p>Abstract</p> <p>Background</p> <p>Today’s biological experiments often involve the collaboration of multidisciplinary researchers utilising several high throughput ‘omics platforms. There is a requirement for the details of the experiment to be adequately described using standardised ontologies to enable data preservation, the analysis of the data and to facilitate the export of the data to public repositories. However there are a bewildering number of ontologies, controlled vocabularies, and minimum standards available for use to describe experiments. There is a need for user-friendly software tools to aid laboratory scientists in capturing the experimental information.</p> <p>Results</p> <p>A web application called XperimentR has been developed for use by laboratory scientists, consisting of a browser-based interface and server-side components which provide an intuitive platform for capturing and sharing experimental metadata. Information recorded includes details about the biological samples, procedures, protocols, and experimental technologies, all of which can be easily annotated using the appropriate ontologies. Files and raw data can be imported and associated with the biological samples via the interface, from either users’ computers, or commonly used open-source data repositories. Experiments can be shared with other users, and experiments can be exported in the standard ISA-Tab format for deposition in public databases. XperimentR is freely available and can be installed natively or by using a provided pre-configured Virtual Machine. A guest system is also available for trial purposes.</p> <p>Conclusion</p> <p>We present a web based software application to aid the laboratory scientist to capture, describe and share details about their experiments.</p

Maladaptation and the paradox of robustness in evolution

Background. Organisms use a variety of mechanisms to protect themselves against perturbations. For example, repair mechanisms fix damage, feedback loops keep homeostatic systems at their setpoints, and biochemical filters distinguish signal from noise. Such buffering mechanisms are often discussed in terms of robustness, which may be measured by reduced sensitivity of performance to perturbations. Methodology/Principal Findings. I use a mathematical model to analyze the evolutionary dynamics of robustness in order to understand aspects of organismal design by natural selection. I focus on two characters: one character performs an adaptive task; the other character buffers the performance of the first character against perturbations. Increased perturbations favor enhanced buffering and robustness, which in turn decreases sensitivity and reduces the intensity of natural selection on the adaptive character. Reduced selective pressure on the adaptive character often leads to a less costly, lower performance trait. Conclusions/Significance. The paradox of robustness arises from evolutionary dynamics: enhanced robustness causes an evolutionary reduction in the adaptive performance of the target character, leading to a degree of maladaptation compared to what could be achieved by natural selection in the absence of robustness mechanisms. Over evolutionary time, buffering traits may become layered on top of each other, while the underlying adaptive traits become replaced by cheaper, lower performance components. The paradox of robustness has widespread implications for understanding organismal design

Histiocytoid cardiomyopathy and microphthalmia with linear skin defects syndrome: phenotypes linked by truncating variants in NDUFB11

Variants in NDUFB11, which encodes a structural component of complex I of the mitochondrial respiratory chain (MRC), were recently independently reported to cause histiocytoid cardiomyopathy (histiocytoid CM) and microphthalmia with linear skin defects syndrome (MLS syndrome). Here we report an additional case of histiocytoid CM, which carries a de novo nonsense variant in NDUFB11 (ENST00000276062.8: c.262C > T; p.[Arg88*]) identified using whole-exome sequencing (WES) of a family trio. An identical variant has been previously reported in association with MLS syndrome. The case we describe here lacked the diagnostic features of MLS syndrome, but a detailed clinical comparison of the two cases revealed significant phenotypic overlap. Heterozygous variants in HCCS (which encodes an important mitochondrially targeted protein) and COX7B, which, like NDUFB11, encodes a protein of the MRC, have also previously been identified in MLS syndrome including a case with features of both MLS syndrome and histiocytoid CM. However, a systematic review of WES data from previously published histiocytoid CM cases, alongside four additional cases presented here for the first time, did not identify any variants in these genes. We conclude that NDUFB11 variants play a role in the pathogenesis of both histiocytoid CM and MLS and that these disorders are allelic (genetically related)

Building relationships: how zoos and other partners can contribute to the conservation of wild orangutans

With both species of orangutan now listed as critically endangered, orangutan conservation needs some critical rethinking. Habitat loss, degradation and fragmentation, and hunting are continuing to push their populations towards further decline. Conservation efforts focusing on rehabilitation and habitat protection are in place but are insufficient unless we move towards a landscape approach that will aim at protecting and connecting areas rather than isolated patches of forest. Conservationists need to engage with communities and industry to really protect the species at a landscape level. This paper explores the current efforts in orangutan conservation on the ground and from the zoo community and new areas emerging to contribute to these new approaches needed to positively impact orangutan populations on the ground

Recombination rate and selection strength in HIV intra-patient evolution

The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the parameters governing genetic diversification and the strength of selection need to be known. While mutation rates can be measured in single replication cycles, the relevant effective recombination rate depends on the probability of coinfection of a cell with more than one virus and can only be inferred from population data. However, most population genetic estimators for recombination rates assume absence of selection and are hence of limited applicability to HIV, since positive and purifying selection are important in HIV evolution. Here, we estimate the rate of recombination and the distribution of selection coefficients from time-resolved sequence data tracking the evolution of HIV within single patients. By examining temporal changes in the genetic composition of the population, we estimate the effective recombination to be r=1.4e-5 recombinations per site and generation. Furthermore, we provide evidence that selection coefficients of at least 15% of the observed non-synonymous polymorphisms exceed 0.8% per generation. These results provide a basis for a more detailed understanding of the evolution of HIV. A particularly interesting case is evolution in response to drug treatment, where recombination can facilitate the rapid acquisition of multiple resistance mutations. With the methods developed here, more precise and more detailed studies will be possible, as soon as data with higher time resolution and greater sample sizes is available.Comment: to appear in PLoS Computational Biolog

Casimir effect of electromagnetic field in Randall-Sundrum spacetime

We study the finite temperature Casimir effect on a pair of parallel perfectly conducting plates in Randall-Sundrum model without using scalar field analogy. Two different ways of interpreting perfectly conducting conditions are discussed. The conventional way that uses perfectly conducting condition induced from 5D leads to three discrete mode corrections. This is very different from the result obtained from imposing 4D perfectly conducting conditions on the 4D massless and massive vector fields obtained by decomposing the 5D electromagnetic field. The latter only contains two discrete mode corrections, but it has a continuum mode correction that depends on the thicknesses of the plates. It is shown that under both boundary conditions, the corrections to the Casimir force make the Casimir force more attractive. The correction under 4D perfectly conducting condition is always smaller than the correction under the 5D induced perfectly conducting condition. These statements are true at any temperature.Comment: 20 pages, 4 figure

Survival and health economic outcomes in heart failure diagnosed at hospital admission versus community settings: a propensity-matched analysis

BACKGROUND AND AIMS: Most patients with heart failure (HF) are diagnosed following a hospital admission. The clinical and health economic impacts of index HF diagnosis made on admission to hospital versus community settings are not known. METHODS: We used the North West London Discover database to examine 34 208 patients receiving an index diagnosis of HF between January 2015 and December 2020. A propensity score-matched (PSM) cohort was identified to adjust for differences in socioeconomic status, cardiovascular risk and pre-diagnosis health resource utilisation cost. Outcomes were stratified by two pathways to index HF diagnosis: a 'hospital pathway' was defined by diagnosis following hospital admission; and a 'community pathway' by diagnosis via a general practitioner or outpatient services. The primary clinical and health economic endpoints were all-cause mortality and cost-consequence differential, respectively. RESULTS: The diagnosis of HF was via hospital pathway in 68% (23 273) of patients. The PSM cohort included 17 174 patients (8582 per group) and was matched across all selected confounders (p>0.05). The ratio of deaths per person-months at 24 months comparing community versus hospital diagnosis was 0.780 (95% CI 0.722 to 0.841, p<0.0001). By 72 months, the ratio of deaths was 0.960 (0.905 to 1.020, p=0.18). Diagnosis via hospital pathway incurred an overall extra longitudinal cost of £2485 per patient. CONCLUSIONS: Index diagnosis of HF through hospital admission continues to dominate and is associated with a significantly greater short-term risk of mortality and substantially increased long-term costs than if first diagnosed in the community. This study highlights the potential for community diagnosis-early, before symptoms necessitate hospitalisation-to improve both clinical and health economic outcomes

Strangeness Content in the Nucleon

I review recent studies of strangeness content in the nucleon pertaining to the flavor-singlet $g_A^0$, the $\bar{s}s$ matrix element and the strangeness electric and magnetic form factors $G_E^s(q^2)$ and $G_M^s(q^2)$, based on lattice QCD calculations. I shall also discuss the relevance of incorporating the strangeness content in nuclei in regard to strange baryon-antibaryon productions from proton-nucleus and nucleus-nucleus collisions at SPS and RHIC energies.Comment: 11 pages, 4 figures, Invited talk at V Int. Conf. on Strangeness in Quark Matter, Berkeley, CA, July 20--25, 200

Diameter-independent skyrmion Hall angle observed in chiral magnetic multilayers

Magnetic skyrmions are topologically non-trivial nanoscale objects. Their topology, which originates in their chiral domain wall winding, governs their unique response to a motion inducing force. When subjected to an electrical current, the chiral winding of the spin texture leads to a deflection of the skyrmion trajectory, characterised by an angle with respect to the applied force direction. This skyrmion Hall angle is predicted to be skyrmion diameter dependent. In contrast, our experimental study finds that the skyrmion Hall angle is diameter independent for skyrmions with diameters ranging from 35 to 825 nm. At an average velocity of 6 ± 1 ms−1, the average skyrmion Hall angle was measured to be 9° ± 2°. In fact, the skyrmion dynamics is dominated by the local energy landscape such as materials defects and the local magnetic configuration

The effectiveness of neuromuscular warm-up strategies, that require no additional equipment, for preventing lower limb injuries during sports participation: a systematic review

PMCID: PMC3408383The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/75. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited