369 research outputs found

    Does detection range matter for inferring social networks in a benthic shark using acoustic telemetry?

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    Accurately estimating contacts between animals can be critical in ecological studies such as examining social structure, predator–prey interactions or transmission of information and disease. While biotelemetry has been used successfully for such studies in terrestrial systems, it is still under development in the aquatic environment. Acoustic telemetry represents an attractive tool to investigate spatio-temporal behaviour of marine fish and has recently been suggested for monitoring underwater animal interactions. To evaluate the effectiveness of acoustic telemetry in recording interindividual contacts, we compared co-occurrence matrices deduced from three types of acoustic receivers varying in detection range in a benthic shark species. Our results demonstrate that (i) associations produced by acoustic receivers with a large detection range (i.e. Vemco VR2W) were significantly different from those produced by receivers with smaller ranges (i.e. Sonotronics miniSUR receivers and proximity loggers) and (ii) the position of individuals within their network, or centrality, also differed. These findings suggest that acoustic receivers with a large detection range may not be the best option to represent true social networks in the case of a benthic marine animal. While acoustic receivers are increasingly used by marine ecologists, we recommend users first evaluate the influence of detection range to depict accurate individual interactions before using these receivers for social or predator–prey studies. We also advocate for combining multiple receiver types depending on the ecological question being asked and the development of multi-sensor tags or testing of new automated proximity loggers, such as the Encounternet system, to improve the precision and accuracy of social and predator–prey interaction studies

    Beam Dynamics and First Operation of the Sub-Harmonic Bunching System in the CTF3 Injector

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    The CLIC Test Facility 3 (CTF3), built at CERN by an international collaboration, aims at demonstrating the feasibility of the CLIC scheme by 2010. The CTF3 drive beam generation scheme relies on the use of a fast phase switch of a sub-harmonic bunching system in order to phase-code the bunches. The amount of charge in unwanted satellite bunches is an important quantity, which must be minimized. Beam dynamic simulations have been used to study the problem, showing the limitation of the present CTF3 design and the gain of potential upgrades. In this paper the results are discussed and compared with beam measurements taken during the first operation of the system

    Engineering of Three-Finger Fold Toxins Creates Ligands with Original Pharmacological Profiles for Muscarinic and Adrenergic Receptors

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    Protein engineering approaches are often a combination of rational design and directed evolution using display technologies. Here, we test “loop grafting,” a rational design method, on three-finger fold proteins. These small reticulated proteins have exceptional affinity and specificity for their diverse molecular targets, display protease-resistance, and are highly stable and poorly immunogenic. The wealth of structural knowledge makes them good candidates for protein engineering of new functionality. Our goal is to enhance the efficacy of these mini-proteins by modifying their pharmacological properties in order to extend their use in imaging, diagnostics and therapeutic applications. Using the interaction of three-finger fold toxins with muscarinic and adrenergic receptors as a model, chimeric toxins have been engineered by substituting loops on toxin MT7 by those from toxin MT1. The pharmacological impact of these grafts was examined using binding experiments on muscarinic receptors M1 and M4 and on the α1A-adrenoceptor. Some of the designed chimeric proteins have impressive gain of function on certain receptor subtypes achieving an original selectivity profile with high affinity for muscarinic receptor M1 and α1A-adrenoceptor. Structure-function analysis supported by crystallographic data for MT1 and two chimeras permits a molecular based interpretation of these gains and details the merits of this protein engineering technique. The results obtained shed light on how loop permutation can be used to design new three-finger proteins with original pharmacological profiles

    Modulating signaling networks by CRISPR/Cas9-mediated transposable element insertion

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    In a recent past, transposable elements (TEs) were referred to as selfish genetic components only capable of copying themselves with the aim of increasing the odds of being inherited. Nonetheless, TEs have been initially proposed as positive control elements acting in synergy with the host. Nowadays, it is well known that TE movement into host genome comprises an important evolutionary mechanism capable of increasing the adaptive fitness. As insights into TE functioning are increasing day to day, the manipulation of transposition has raised an interesting possibility of setting the host functions, although the lack of appropriate genome engineering tools has unpaved it. Fortunately, the emergence of genome editing technologies based on programmable nucleases, and especially the arrival of a multipurpose RNA-guided Cas9 endonuclease system, has made it possible to reconsider this challenge. For such purpose, a particular type of transposons referred to as miniature inverted-repeat transposable elements (MITEs) has shown a series of interesting characteristics for designing functional drivers. Here, recent insights into MITE elements and versatile RNA-guided CRISPR/Cas9 genome engineering system are given to understand how to deploy the potential of TEs for control of the host transcriptional activity.Fil: Vaschetto, Luis Maria Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Diversidad Animal I; Argentin

    A randomised phase II multicentre trial of irinotecan (CPT-11) using four different schedules in patients with metastatic colorectal cancer

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    The purpose of this phase II trial was to compare the efficacy, safety and pharmacokinetics of four irinotecan schedules for the treatment of metastatic colorectal cancer. In total, 174 5-fluorouracil pretreated patients were randomised to: arm A (n=41), 350 mg m(-2) irinotecan as a 90-min i.v. infusion q3 weeks; arm B (n=38), 125 mg m(-2) irinotecan as a 90-min i.v. infusion weekly x 4 weeks q6 weeks; arm C (n=46), 250 mg m(-2) irinotecan as a 90-min i.v. infusion q2 weeks; or arm D (n=49), 10 mg m(-2) day(-1) irinotecan as a 14-day continuous infusion q3 weeks. No significant differences in efficacy across the four arms were observed, although a shorter time to treatment failure was noted for arm D (1.7 months; P=0.02). Overall response rates were in the range 5-11%. Secondary end points included median survival (6.4-9.4 months), and time to progression (2.7-3.8 months) and treatment failure (1.7-3.2 months). Similarly, there were no significant differences in the incidence of grade 3-4 toxicities, although the toxicity profile between arms A, B, and C and D did differ. Generally, significantly less haematologic toxicity, alopecia and cholinergic syndrome were observed in arm D; however, there was a trend for increased gastrointestinal toxicity. Irinotecan is an effective and safe second-line treatment for colorectal cancer. The schedules examined yielded equivalent results, indicating that there is no advantage of the prolonged vs short infusion schedule

    Isolation rearing does not constrain social plasticity in a family-living lizard

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    Financial support for this research was provided by the Australian Research Council (ARC DP130102998, grant to MJW and RWB), Natural Sciences and Engineering Research Council of Canada (scholarship to JLR), the Australasian Society for the Study of Animal Behavior, the Australian Museum, and Macquarie University (scholarship to JLR). DWAN was supported by an ARC Discovery Early Career Research Award (DE150101774) and University of New South Wales Vice Chancellors Fellowship.An animal’s social environment can be both dynamic and complex. Thus, social species often garner fitness benefits through being plastic in their social behavior. Yet, social plasticity can be constrained by an individual’s experience. We examined the influence of early social environment on social behavior in the tree skink (Egernia striolata), a family-living lizard. In the first phase of this study, we reared juveniles in 2 different social environments for 1.5 years: either in isolation or in unrelated pairs. We quantified each lizard’s sociability at 4-month intervals using a standardized laboratory assay and found that isolated lizards were more sociable, spending the assay closer to an adult female, than socially-reared lizards. In the second phase of this study (at the end of 1.5 years), we released all lizards into a semi-natural environment, observed their associations, and used social network analysis to quantify social behavior. During the initial 6 weeks post-release, we detected no differences in social behavior between rearing treatments. However, during the following 6 months differences emerged. Isolated lizards were more homogeneous in the strength of their associations than socially-reared lizards. Also, at first, isolated lizards associated more strongly than socially-reared lizards. Over time, isolated lizard associations became weaker and involved fewer lizards. In contrast, the level and number of associations of socially-reared lizards were stable over time. Our findings suggest that early experience influences tree skink social behavior but does not constrain social plasticity: isolation rearing did not limit their ability to respond to a novel social environment.PostprintPeer reviewe

    CTF3 Design Report: Preliminary Phase

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    The design of CLIC is based on a two-beam scheme, where the short pulses of high power 30 GHz RF are extracted from a drive beam running parallel to the main beam. The 3rd generation CLIC Test Facility (CTF3) will demonstrate the generation of the drive beam with the appropriate time structure, the extraction of 30 GHz RF power from this beam, as well as acceleration of a probe beam with 30 GHz RF cavities. The project makes maximum use of existing equipment and infrastructure of the LPI complex, which became available after the closure of LEP. In the first stage of the project, the "Preliminary Phase", the existing LIL linac and the EPA ring, both modified to suit the new requirements, are used to investigate the technique of frequency multiplication by means of interleaving bunches from subsequent trains. This report describes the design of this phase

    A Detailed History of Intron-rich Eukaryotic Ancestors Inferred from a Global Survey of 100 Complete Genomes

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    Protein-coding genes in eukaryotes are interrupted by introns, but intron densities widely differ between eukaryotic lineages. Vertebrates, some invertebrates and green plants have intron-rich genes, with 6–7 introns per kilobase of coding sequence, whereas most of the other eukaryotes have intron-poor genes. We reconstructed the history of intron gain and loss using a probabilistic Markov model (Markov Chain Monte Carlo, MCMC) on 245 orthologous genes from 99 genomes representing the three of the five supergroups of eukaryotes for which multiple genome sequences are available. Intron-rich ancestors are confidently reconstructed for each major group, with 53 to 74% of the human intron density inferred with 95% confidence for the Last Eukaryotic Common Ancestor (LECA). The results of the MCMC reconstruction are compared with the reconstructions obtained using Maximum Likelihood (ML) and Dollo parsimony methods. An excellent agreement between the MCMC and ML inferences is demonstrated whereas Dollo parsimony introduces a noticeable bias in the estimations, typically yielding lower ancestral intron densities than MCMC and ML. Evolution of eukaryotic genes was dominated by intron loss, with substantial gain only at the bases of several major branches including plants and animals. The highest intron density, 120 to 130% of the human value, is inferred for the last common ancestor of animals. The reconstruction shows that the entire line of descent from LECA to mammals was intron-rich, a state conducive to the evolution of alternative splicing

    I-eAT, a consortium addressing gastronomic solutions for altered taste: A research and development manifesto

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    An International Altered Taste Consortium (I-eAT) is proposed that seeks to utilise gastronomic and biopsychosocial insights to understand and help people who experience taste alterations. Altered eating experiences and a changed experience of taste is a common and disabling trans-diagnostic, multi-causal entity which has for too long been poorly understood and supported in health research and practice. The phrase Altered Taste is employed (using “taste” in its most commonly understood sense to refer to the overall multi-sensory flavour experience) to emphasise the lived sensory experience of those living with an altered relationship with food. Interdisciplinary collaboration between the domains of medicine, health care, physiology, psychology and gastronomy is considered key to understanding, working with and improving altered taste. This manifesto emerged from ongoing research and practice, and was formulated at a workshop of interdisciplinary experts and patient representatives at the Second International Altered Taste Symposium (2022). Between them they collectively agreed on 1. A shared terminology to maximise stakeholder involvement and 2. An overall research aim to better understand, manage and treat Altered Taste. This aim is implemented in 4 key research objectives
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