At What Cost? Trade-Offs and Influences on Energetic Investment in Tail Regeneration in Lizards Following Autotomy.

Caudal autotomy, the ability to shed a portion of the tail, is a widespread defence strategy among lizards. Following caudal autotomy, and during regeneration, lizards face both short- and long-term costs associated with the physical loss of the tail and the energy required for regeneration. As such, the speed at which the individual regenerates its tail (regeneration rate) should reflect the fitness priorities of the individual. However, multiple factors influence the regeneration rate in lizards, making inter-specific comparisons difficult and hindering broader scale investigations. We review regeneration rates for lizards and tuatara from the published literature, discuss how species' fitness priorities and regeneration rates are influenced by specific, life history and environmental factors, and provide recommendations for future research. Regeneration rates varied extensively (0-4.3 mm/day) across the 56 species from 14 family groups. Species-specific factors, influencing regeneration rates, varied based on the type of fracture plane, age, sex, reproductive season, and longevity. Environmental factors including temperature, photoperiod, nutrition, and stress also affected regeneration rates, as did the method of autotomy induction, and the position of the tail also influenced regeneration rates for lizards. Additionally, regeneration could alter an individual's behaviour, growth, and reproductive output, but this varied depending on the species

Extraction and inhibition of enzymatic activity of botulinum neurotoxins /B1, /B2, /B3, /B4, and /B5 by a panel of monoclonal anti-BoNT/B antibodies

<p>Abstract</p> <p>Background</p> <p>Botulism is caused by botulinum neurotoxins (BoNTs), extremely toxic proteins which can induce respiratory failure leading to long-term intensive care or death. Treatment for botulism includes administration of antitoxins, which must be administered early in the course of the intoxication; therefore, rapid determination of human exposure to BoNT is an important public health goal. In previous work, our laboratory reported on Endopep-MS, a mass spectrometry-based activity method for detecting and differentiating BoNT/A, /B, /E, and /F in clinical samples. We also demonstrated that antibody-capture is effective for purification and concentration of BoNTs from complex matrices such as clinical samples. However, some antibodies inhibit or neutralize the enzymatic activity of BoNT, so the choice of antibody for toxin extraction is critical.</p> <p>Results</p> <p>In this work, we evaluated 24 anti-BoNT/B monoclonal antibodies (mAbs) for their ability to inhibit the <it>in vitro </it>activity of BoNT/B1, /B2, /B3, /B4, and /B5 and to extract those toxins. Among the mAbs, there were significant differences in ability to extract BoNT/B subtypes and inhibitory effect on BoNT catalytic activity. Some of the mAbs tested enhanced the <it>in vitro </it>light chain activity of BoNT/B, suggesting that BoNT/B may undergo conformational change upon binding some mAbs.</p> <p>Conclusions</p> <p>In addition to determining <it>in vitro </it>inhibition abilities of a panel of mAbs against BoNT/B1-/B5, this work has determined B12.2 and 2B18.2 to be the best mAbs for sample preparation before Endopep-MS. These mAb characterizations also have the potential to assist with mechanistic studies of BoNT/B protection and treatment, which is important for studying alternative therapeutics for botulism.</p

Game-Play Breakdowns and Breakthroughs: Exploring the Relationship Between Action, Understanding, and Involvement

Game developers have to ensure their games are appealing to, and playable by, a range of people. However, although there has been interest in the game-play experience, we know little about how learning relates to player involvement. This is despite challenge being an integral part of game-play, providing players with potential opportunities to learn. This article reports on a multiple case-study approach that explored how learning and involvement come together in practice. Participants consisted of a mix of gamers and casual players. Data included interviews, multiple observations of game-play, postplay cued interviews, and diary entries. A set of theoretical claims representing suggested relationships between involvement and learning were developed on the basis of previous literature; these were then assessed through a critical examination of the data set. The resulting theory is presented as 14 refined claims that relate to micro and macro involvement; breakdowns and breakthroughs in action, understanding, and involvement; progress; and agency, meaning and compelling game-play. The claims emphasize how players experience learning via breakthroughs in understanding, where involvement is increased when the player feels responsible for progress. Supporting the relationship between learning and involvement is important for ensuring the success of commercial and educational games

Testing the Nambu-Goldstone Hypothesis for Quarks and Leptons at the LHC

The hierarchy of the Yukawa couplings is an outstanding problem of the standard model. We present a class of models in which the first and second generation fermions are SUSY partners of pseudo-Nambu-Goldstone bosons that parameterize a non-compact Kahler manifold, explaining the small values of these fermion masses relative to those of the third generation. We also provide an example of such a model. We find that various regions of the parameter space in this scenario can give the correct dark matter abundance, and that nearly all of these regions evade other phenomenological constraints. We show that for gluino mass ~700 GeV, model points from these regions can be easily distinguished from other mSUGRA points at the LHC with only 7 fb^(-1) of integrated luminosity at 14 TeV. The most striking signatures are a dearth of b- and tau-jets, a great number of multi-lepton events, and either an "inverted" slepton mass hierarchy, narrowed slepton mass hierarchy, or characteristic small-mu spectrum.Comment: Corresponds to published versio

A Two-Tiered Correlation of Dark Matter with Missing Transverse Energy: Reconstructing the Lightest Supersymmetric Particle Mass at the LHC

We suggest that non-trivial correlations between the dark matter particle mass and collider based probes of missing transverse energy H_T^miss may facilitate a two tiered approach to the initial discovery of supersymmetry and the subsequent reconstruction of the LSP mass at the LHC. These correlations are demonstrated via extensive Monte Carlo simulation of seventeen benchmark models, each sampled at five distinct LHC center-of-mass beam energies, spanning the parameter space of No-Scale F-SU(5).This construction is defined in turn by the union of the Flipped SU(5) Grand Unified Theory, two pairs of hypothetical TeV scale vector-like supersymmetric multiplets with origins in F-theory, and the dynamically established boundary conditions of No-Scale Supergravity. In addition, we consider a control sample comprised of a standard minimal Supergravity benchmark point. Led by a striking similarity between the H_T^miss distribution and the familiar power spectrum of a black body radiator at various temperatures, we implement a broad empirical fit of our simulation against a Poisson distribution ansatz. We advance the resulting fit as a theoretical blueprint for deducing the mass of the LSP, utilizing only the missing transverse energy in a statistical sampling of >= 9 jet events. Cumulative uncertainties central to the method subsist at a satisfactory 12-15% level. The fact that supersymmetric particle spectrum of No-Scale F-SU(5) has thrived the withering onslaught of early LHC data that is steadily decimating the Constrained Minimal Supersymmetric Standard Model and minimal Supergravity parameter spaces is a prime motivation for augmenting more conventional LSP search methodologies with the presently proposed alternative.Comment: JHEP version, 17 pages, 9 Figures, 2 Table

Baby Business: a randomised controlled trial of a universal parenting program that aims to prevent early infant sleep and cry problems and associated parental depression

<p>Abstract</p> <p>Background</p> <p>Infant crying and sleep problems (e.g. frequent night waking, difficulties settling to sleep) each affect up to 30% of infants and often co-exist. They are costly to manage and associated with adverse outcomes including postnatal depression symptoms, early weaning from breast milk, and later child behaviour problems. Preventing such problems could improve these adverse outcomes and reduce costs to families and the health care system. Anticipatory guidance-i.e. providing parents with information about normal infant sleep and cry patterns, ways to encourage self-settling in infants, and ways to develop feeding and settling routines <it>before </it>the onset of problems-could prevent such problems. This paper outlines the protocol for our study which aims to test an anticipatory guidance approach.</p> <p>Methods/Design</p> <p>750 families from four Local Government Areas in Melbourne, Australia have been randomised to receive the <it>Baby Business </it>program (intervention group) or usual care (control group) offered by health services. The <it>Baby Business </it>program provides parents with information about infant sleep and crying via a DVD and booklet (mailed soon after birth), telephone consultation (at infant age 6-8 weeks) and parent group session (at infant age 12 weeks). All English speaking parents of healthy newborn infants born at > 32 weeks gestation and referred by their maternal and child health nurse at their first post partum home visit (day 7-10 postpartum), are eligible. The primary outcome is parent report of infant night time sleep as a problem at four months of age and secondary outcomes include parent report of infant daytime sleep or crying as a problem, mean duration of infant sleep and crying/24 hours, parental depression symptoms, parent sleep quality and quantity and health service use. Data will be collected at two weeks (baseline), four months and six months of age. An economic evaluation using a cost-consequences approach will, from a societal perspective, compare costs and health outcomes between the intervention and control groups.</p> <p>Discussion</p> <p>To our knowledge this is the first randomised controlled trial of a program which aims to prevent both infant sleeping and crying problems and associated postnatal depression symptoms. If effective, it could offer an important public health prevention approach to these common, distressing problems.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN63834603">ISRCTN63834603</a></p

How generic is cosmic string formation in SUSY GUTs

We study cosmic string formation within supersymmetric grand unified theories. We consider gauge groups having a rank between 4 and 8. We examine all possible spontaneous symmetry breaking patterns from the GUT down to the standard model gauge group. Assuming standard hybrid inflation, we select all the models which can solve the GUT monopole problem, lead to baryogenesis after inflation and are consistent with proton lifetime measurements. We conclude that in all acceptable spontaneous symmetry breaking schemes, cosmic string formation is unavoidable. The strings which form at the end of inflation have a mass which is proportional to the inflationary scale. Sometimes, a second network of strings form at a lower scale. Models based on gauge groups which have rank greater than 6 can lead to more than one inflationary era; they all end by cosmic string formation.Comment: 31 pages, Latex, submitted to PR

Differential protein profiling as a potential multi-marker approach for TSE diagnosis

Rona Barron - ORCID: 0000-0003-4512-9177 https://orcid.org/0000-0003-4512-9177This "proof of concept" study, examines the use of differential protein expression profiling using surface enhanced laser desorption and ionisationtime of flight mass spectrometry (SELDI-TOF) for the diagnosis of TSE disease. Spectral output from all proteins selectively captured from individual murine brain homogenate samples, are compared as "profiles" in groups of infected and non-infected animals. Differential protein expression between groups is thus highlighted and statistically significant protein "peaks" used to construct a panel of disease specific markers. Studies at both terminal stages of disease and throughout the time course of disease have shown a disease specific protein profile or "disease fingerprint" which could be used to distinguish between groups of TSE infected and uninfected animals at an early time point of disease. Results Our results show many differentially expressed proteins in diseased and control animals, some at early stages of disease. Three proteins identified by SELDI-TOF analysis were verified by immunohistochemistry in brain tissue sections. We demonstrate that by combining the most statistically significant changes in expression, a panel of markers can be constructed that can distinguish between TSE diseased and normal animals. Conclusion Differential protein expression profiling has the potential to be used for the detection of disease in TSE infected animals. Having established that a "training set" of potential markers can be constructed, more work would be required to further test the specificity and sensitivity of the assay in a "testing set". Based on these promising results, further studies are being performed using blood samples from infected sheep to assess the potential use of SELDI-TOF as a pre-mortem blood based diagnostic.https://doi.org/10.1186/1471-2334-9-1889pubpub

Extraction and Inhibition of Enzymatic Activity of Botulinum Neurotoxins/A1, /A2, and /A3 by a Panel of Monoclonal Anti-BoNT/A Antibodies

Botulinum neurotoxins (BoNTs) are extremely potent toxins that are capable of causing death or respiratory failure leading to long-term intensive care. Treatment includes serotype-specific antitoxins, which must be administered early in the course of the intoxication. Rapidly determining human exposure to BoNT is an important public health goal. In previous work, our laboratory focused on developing Endopep-MS, a mass spectrometry-based endopeptidase method for detecting and differentiating BoNT/A–G serotypes in buffer and BoNT/A, /B, /E, and /F in clinical samples. We have previously reported the effectiveness of antibody-capture to purify and concentrate BoNTs from complex matrices, such as clinical samples. Because some antibodies inhibit or neutralize the activity of BoNT, the choice of antibody with which to extract the toxin is critical. In this work, we evaluated a panel of 16 anti-BoNT/A monoclonal antibodies (mAbs) for their ability to inhibit the in vitro activity of BoNT/A1, /A2, and /A3 complex as well as the recombinant LC of A1. We also evaluated the same antibody panel for the ability to extract BoNT/A1, /A2, and /A3. Among the mAbs, there were significant differences in extraction efficiency, ability to extract BoNT/A subtypes, and inhibitory effect on BoNT catalytic activity. The mAbs binding the C-terminal portion of the BoNT/A heavy chain had optimal properties for use in the Endopep-MS assay