239 research outputs found

    Honeybees' Speed Depends on Dorsal as Well as Lateral, Ventral and Frontal Optic Flows

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    Flying insects use the optic flow to navigate safely in unfamiliar environments, especially by adjusting their speed and their clearance from surrounding objects. It has not yet been established, however, which specific parts of the optical flow field insects use to control their speed. With a view to answering this question, freely flying honeybees were trained to fly along a specially designed tunnel including two successive tapering parts: the first part was tapered in the vertical plane and the second one, in the horizontal plane. The honeybees were found to adjust their speed on the basis of the optic flow they perceived not only in the lateral and ventral parts of their visual field, but also in the dorsal part. More specifically, the honeybees' speed varied monotonically, depending on the minimum cross-section of the tunnel, regardless of whether the narrowing occurred in the horizontal or vertical plane. The honeybees' speed decreased or increased whenever the minimum cross-section decreased or increased. In other words, the larger sum of the two opposite optic flows in the horizontal and vertical planes was kept practically constant thanks to the speed control performed by the honeybees upon encountering a narrowing of the tunnel. The previously described ALIS (“AutopiLot using an Insect-based vision System”) model nicely matches the present behavioral findings. The ALIS model is based on a feedback control scheme that explains how honeybees may keep their speed proportional to the minimum local cross-section of a tunnel, based solely on optic flow processing, without any need for speedometers or rangefinders. The present behavioral findings suggest how flying insects may succeed in adjusting their speed in their complex foraging environments, while at the same time adjusting their distance not only from lateral and ventral objects but also from those located in their dorsal visual field

    Antiepileptic drugs’ tolerability and safety – a systematic review and meta-analysis of adverse effects in dogs

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    <p>Various anti-epileptic drugs (AEDs) are used for the management of idiopathic epilepsy (IE) in dogs. Their safety profile is an important consideration for regulatory bodies, owners and prescribing clinicians. However, information on their adverse effects still remains limited with most of it derived from non-blinded non-randomized uncontrolled trials and case reports.</p><p><span>This poster won third place, which was presented at the Veterinary Evidence Today conference, Edinburgh November 1-3, 2016. </span></p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /

    Gene expression profiling identifies distinct molecular subgroups of leiomyosarcoma with clinical relevance

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    YesBackground: Soft tissue sarcomas are heterogeneous and a major complication in their management is that the existing classification scheme is not definitive and is still evolving. Leiomyosarcomas, a major histologic category of soft tissue sarcomas, are malignant tumours displaying smooth muscle differentiation. Although defined as a single group, they exhibit a wide range of clinical behaviour. We aimed to carry out molecular classification to identify new molecular subgroups with clinical relevance. Methods: We used gene expression profiling on 20 extra-uterine leiomyosarcomas and cross-study analyses for molecular classification of leiomyosarcomas. Clinical significance of the subgroupings was investigated. Results: We have identified two distinct molecular subgroups of leiomyosarcomas. One group was characterised by high expression of 26 genes that included many genes from the sub-classification gene cluster proposed by Nielsen et al. These sub-classification genes include genes that have importance structurally, as well as in cell signalling. Notably, we found a statistically significant association of the subgroupings with tumour grade. Further refinement led to a group of 15 genes that could recapitulate the tumour subgroupings in our data set and in a second independent sarcoma set. Remarkably, cross-study analyses suggested that these molecular subgroups could be found in four independent data sets, providing strong support for their existence. Conclusions: Our study strongly supported the existence of distinct leiomyosarcoma molecular subgroups, which have clinical association with tumour grade. Our findings will aid in advancing the classification of leiomyosarcomas and lead to more individualised and better management of the disease.Alexander Boag Sarcoma Fund

    Whistle communication in mammal-eating killer whales (Orcinus orca): further evidence for acoustic divergence between ecotypes

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    Public signaling plays an important role in territorial and sexual displays in animals; however, in certain situations, it is advantageous to keep signaling private to prevent eavesdropping by unintended receivers. In the northeastern Pacific, two populations of killer whales (Orcinus orca), fish-eating “resident” killer whales and mammal-eating “transient” killer whales, share the same habitat. Previous studies have shown that residents use whistles as private signals during close-range communication, where they probably serve to coordinate behavioral interactions. Here, we investigated the whistling behavior of mammal-eating killer whales, and, based on divergent social structures and social behaviors between residents and transients, we predicted to find differences in both whistle usage and whistle parameters. Our results show that, like resident killer whales, transients produce both variable and stereotyped whistles. However, clear differences in whistle parameters between ecotypes show that the whistle repertoire of mammal-eating killer whales is clearly distinct from and less complex than that of fish-eating killer whales. Furthermore, mammal-eating killer whales only produce whistles during “milling after kill” and “surface-active” behaviors, but are almost completely silent during all other activities. Nonetheless, whistles of transient killer whales may still serve a role similar to that of resident killer whales. Mammal-eating killer whales seem to be under strong selection to keep their communication private from potential prey (whose hearing ranges overlap with that of killer whales), and they appear to accomplish this mainly by restricting vocal activity rather than by changes in whistle parameters

    Caenorhabditis briggsae Recombinant Inbred Line Genotypes Reveal Inter-Strain Incompatibility and the Evolution of Recombination

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    The nematode Caenorhabditis briggsae is an emerging model organism that allows evolutionary comparisons with C. elegans and exploration of its own unique biological attributes. To produce a high-resolution C. briggsae recombination map, recombinant inbred lines were generated from reciprocal crosses between two strains and genotyped at over 1,000 loci. A second set of recombinant inbred lines involving a third strain was also genotyped at lower resolution. The resulting recombination maps exhibit discrete domains of high and low recombination, as in C. elegans, indicating these are a general feature of Caenorhabditis species. The proportion of a chromosome's physical size occupied by the central, low-recombination domain is highly correlated between species. However, the C. briggsae intra-species comparison reveals striking variation in the distribution of recombination between domains. Hybrid lines made with the more divergent pair of strains also exhibit pervasive marker transmission ratio distortion, evidence of selection acting on hybrid genotypes. The strongest effect, on chromosome III, is explained by a developmental delay phenotype exhibited by some hybrid F2 animals. In addition, on chromosomes IV and V, cross direction-specific biases towards one parental genotype suggest the existence of cytonuclear epistatic interactions. These interactions are discussed in relation to surprising mitochondrial genome polymorphism in C. briggsae, evidence that the two strains diverged in allopatry, the potential for local adaptation, and the evolution of Dobzhansky-Muller incompatibilities. The genetic and genomic resources resulting from this work will support future efforts to understand inter-strain divergence as well as facilitate studies of gene function, natural variation, and the evolution of recombination in Caenorhabditis nematodes

    Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to targeted therapy.

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    BACKGROUND: Sporadic vascular malformations (VMs) are complex congenital anomalies of blood vessels that lead to stroke, life-threatening bleeds, disfigurement, overgrowth, and/or pain. Therapeutic options are severely limited, and multidisciplinary management remains challenging, particularly for high-flow arteriovenous malformations (AVM). METHODS: To investigate the pathogenesis of sporadic intracranial and extracranial VMs in 160 children in which known genetic causes had been excluded, we sequenced DNA from affected tissue and optimized analysis for detection of low mutant allele frequency. RESULTS: We discovered multiple mosaic-activating variants in 4 genes of the RAS/MAPK pathway, KRAS, NRAS, BRAF, and MAP2K1, a pathway commonly activated in cancer and responsible for the germline RAS-opathies. These variants were more frequent in high-flow than low-flow VMs. In vitro characterization and 2 transgenic zebrafish AVM models that recapitulated the human phenotype validated the pathogenesis of the mutant alleles. Importantly, treatment of AVM-BRAF mutant zebrafish with the BRAF inhibitor vemurafinib restored blood flow in AVM. CONCLUSION: Our findings uncover a major cause of sporadic VMs of different clinical types and thereby offer the potential of personalized medical treatment by repurposing existing licensed cancer therapies. FUNDING: This work was funded or supported by grants from the AVM Butterfly Charity, the Wellcome Trust (UK), the Medical Research Council (UK), the UK National Institute for Health Research, the L'Oreal-Melanoma Research Alliance, the European Research Council, and the National Human Genome Research Institute (US)

    Googling Food Webs: Can an Eigenvector Measure Species' Importance for Coextinctions?

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    A major challenge in ecology is forecasting the effects of species' extinctions, a pressing problem given current human impacts on the planet. Consequences of species losses such as secondary extinctions are difficult to forecast because species are not isolated, but interact instead in a complex network of ecological relationships. Because of their mutual dependence, the loss of a single species can cascade in multiple coextinctions. Here we show that an algorithm adapted from the one Google uses to rank web-pages can order species according to their importance for coextinctions, providing the sequence of losses that results in the fastest collapse of the network. Moreover, we use the algorithm to bridge the gap between qualitative (who eats whom) and quantitative (at what rate) descriptions of food webs. We show that our simple algorithm finds the best possible solution for the problem of assigning importance from the perspective of secondary extinctions in all analyzed networks. Our approach relies on network structure, but applies regardless of the specific dynamical model of species' interactions, because it identifies the subset of coextinctions common to all possible models, those that will happen with certainty given the complete loss of prey of a given predator. Results show that previous measures of importance based on the concept of “hubs” or number of connections, as well as centrality measures, do not identify the most effective extinction sequence. The proposed algorithm provides a basis for further developments in the analysis of extinction risk in ecosystems

    A missense variant in CST3 exerts a recessive effect on susceptibility to age-related macular degeneration resembling its association with Alzheimer’s disease

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    Age-related macular degeneration (AMD) and Alzheimer’s disease (AD) are degenerative, multifactorial diseases involving age-related accumulation of extracellular deposits linked to dysregulation of protein homeostasis. Here, we strengthen the evidence that an nsSNP (p.Ala25Thr) in the cysteine proteinase inhibitor cystatin C gene CST3, previously confirmed by meta-analysis to be associated with AD, is associated with exudative AMD. To our knowledge, this is the first report highlighting a genetic variant that increases the risk of developing both AD and AMD. Furthermore, we demonstrate that the risk associated with the mutant allele follows a recessive model for both diseases. We perform an AMD-CST3 case–control study genotyping 350 exudative AMD Caucasian individuals. Bringing together our data with the previously reported AMD-CST3 association study, the evidence of a recessive effect on AMD risk is strengthened (OR = 1.89, P = 0.005). This effect closely resembles the AD-CST3 recessive effect (OR = 1.73, P = 0.005) previously established by meta-analysis. This resemblance is substantiated by the high correlation between CST3 genotype and effect size across the two diseases (R2 = 0.978). A recessive effect is in line with the known function of cystatin C, a potent enzyme inhibitor. Its potency means that, in heterozygous individuals, a single functional allele is sufficient to maintain its inhibitory function; only homozygous individuals will lack this form of proteolytic regulation. Our findings support the hypothesis that recessively acting variants account for some of the missing heritability of multifactorial diseases. Replacement therapy represents a translational opportunity for individuals homozygous for the mutant allele

    Distinguishing the Impacts of Inadequate Prey and Vessel Traffic on an Endangered Killer Whale (Orcinus orca) Population

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    Managing endangered species often involves evaluating the relative impacts of multiple anthropogenic and ecological pressures. This challenge is particularly formidable for cetaceans, which spend the majority of their time underwater. Noninvasive physiological approaches can be especially informative in this regard. We used a combination of fecal thyroid (T3) and glucocorticoid (GC) hormone measures to assess two threats influencing the endangered southern resident killer whales (SRKW; Orcinus orca) that frequent the inland waters of British Columbia, Canada and Washington, U.S.A. Glucocorticoids increase in response to nutritional and psychological stress, whereas thyroid hormone declines in response to nutritional stress but is unaffected by psychological stress. The inadequate prey hypothesis argues that the killer whales have become prey limited due to reductions of their dominant prey, Chinook salmon (Oncorhynchus tshawytscha). The vessel impact hypothesis argues that high numbers of vessels in close proximity to the whales cause disturbance via psychological stress and/or impaired foraging ability. The GC and T3 measures supported the inadequate prey hypothesis. In particular, GC concentrations were negatively correlated with short-term changes in prey availability. Whereas, T3 concentrations varied by date and year in a manner that corresponded with more long-term prey availability. Physiological correlations with prey overshadowed any impacts of vessels since GCs were lowest during the peak in vessel abundance, which also coincided with the peak in salmon availability. Our results suggest that identification and recovery of strategic salmon populations in the SRKW diet are important to effectively promote SRKW recovery

    Multiple-look effects on temporal discrimination within sound sequences

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    The multiple-look notion holds that the difference limen (DL) decreases with multiple observations. We investigated this notion for temporal discrimination in isochronous sound sequences. In Experiment 1, we established a multiple-look effect when sequences comprised nine standard time intervals (S) followed by an increasing number of comparison time intervals (C), but no multiple-look effect when one trailing C interval was preceded by an increasing number of S intervals. In Experiment 2, we extended the design. There were four sequential conditions: (a) 9 leading S intervals followed by 1, 2, …, or 9 C-intervals; (b) 9 leading C intervals followed by 1, 2, …, or 9 S intervals; (c) 9 trailing C-intervals preceded by 1, 2, …, or 9 S-intervals; and (d) 9 trailing S-intervals preceded by 1, 2, …, or 9 C-intervals. Both the interval accretions before and after the tempo change caused multiple-look effects, irrespective of the time order of S and C. Complete deconfounding of the number of intervals before and after the tempo change was accomplished in Experiment 3. The multiple-look effect of interval accretion before the tempo change was twice as big as that after the tempo change. The diminishing returns relation between the DL and interval accretion could be described well by a reciprocal function
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