521 research outputs found

    Vision Impairs the Abilities of Bats to Avoid Colliding with Stationary Obstacles

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    Background: Free-flying insectivorous bats occasionally collide with stationary objects they should easily detect by echolocation and avoid. Collisions often occur with lighted objects, suggesting ambient light may deleteriously affect obstacle avoidance capabilities. We tested the hypothesis that free-flying bats may orient by vision when they collide with some obstacles. We additionally tested whether acoustic distractions, such as ‘‘distress calls’ ’ of other bats, contributed to probabilities of collision. Methodology/Principal Findings: To investigate the role of visual cues in the collisions of free-flying little brown bats (Myotis lucifugus) with stationary objects, we set up obstacles in an area of high bat traffic during swarming. We used combinations of light intensities and visually dissimilar obstacles to verify that bats orient by vision. In early August, bats collided more often in the light than the dark, and probabilities of collision varied with the visibility of obstacles. However, the probabilities of collisions altered in mid to late August, coincident with the start of behavioural, hormonal, and physiological changes occurring during swarming and mating. Distress calls did not distract bats and increase the incidence of collisions. Conclusions/Significance: Our findings indicate that visual cues are more important for free-flying bats than previously recognized, suggesting integration of multi-sensory modalities during orientation. Furthermore, our study highlight

    Predicting the Impact of Long-Term Temperature Changes on the Epidemiology and Control of Schistosomiasis: A Mechanistic Model

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    , the causative agent of schistosomiasis in humans.The model showed that the impact of temperature on disease prevalence and abundance is not straightforward; the mean infection burden in humans increases up to 30°C, but then crashes at 35°C, primarily due to increased mortalities of the snail intermediate host. In addition, increased temperatures changed the dynamics of disease from stable, endemic infection to unstable, epidemic cycles at 35°C. However, the prevalence of infection was largely unchanged by increasing temperatures. Temperature increases also affected the response of the model to changes in each parameter, indicating certain control strategies may become less effective with local temperature changes. At lower temperatures, the most effective single control strategy is to target the adult parasites through chemotherapy. However, as temperatures increase, targeting the snail intermediate hosts, for example through molluscicide use, becomes more effective. will not respond to increased temperatures in a linear fashion, and the optimal control strategy is likely to change as temperatures change. It is only through a mechanistic approach, incorporating the combined effects of temperature on all stages of the life-cycle, that we can begin to predict the consequences of climate change on the incidence and severity of such diseases

    Statistical Inference for Multi-Pathogen Systems

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    There is growing interest in understanding the nature and consequences of interactions among infectious agents. Pathogen interactions can be operational at different scales, either within a co-infected host or in host populations where they co-circulate, and can be either cooperative or competitive. The detection of interactions among pathogens has typically involved the study of synchrony in the oscillations of the protagonists, but as we show here, phase association provides an unreliable dynamical fingerprint for this task. We assess the capacity of a likelihood-based inference framework to accurately detect and quantify the presence and nature of pathogen interactions on the basis of realistic amounts and kinds of simulated data. We show that when epidemiological and demographic processes are well understood, noisy time series data can contain sufficient information to allow correct inference of interactions in multi-pathogen systems. The inference power is dependent on the strength and time-course of the underlying mechanism: stronger and longer-lasting interactions are more easily and more precisely quantified. We examine the limitations of our approach to stochastic temporal variation, under-reporting, and over-aggregation of data. We propose that likelihood shows promise as a basis for detection and quantification of the effects of pathogen interactions and the determination of their (competitive or cooperative) nature on the basis of population-level time-series data

    Modeling allosteric signal propagation using protein structure networks

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    Allosteric communication in proteins can be induced by the binding of effective ligands, mutations or covalent modifications that regulate a site distant from the perturbed region. To understand allosteric regulation, it is important to identify the remote sites that are affected by the perturbation-induced signals and how these allosteric perturbations are transmitted within the protein structure. In this study, by constructing a protein structure network and modeling signal transmission with a Markov random walk, we developed a method to estimate the signal propagation and the resulting effects. In our model, the global perturbation effects from a particular signal initiation site were estimated by calculating the expected visiting time (EVT), which describes the signal-induced effects caused by signal transmission through all possible routes. We hypothesized that the residues with high EVT values play important roles in allosteric signaling. We applied our model to two protein structures as examples, and verified the validity of our model using various types of experimental data. We also found that the hot spots in protein binding interfaces have significantly high EVT values, which suggests that they play roles in mediating signal communication between protein domains

    A structure filter for the Eukaryotic Linear Motif Resource

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    <p>Abstract</p> <p>Background</p> <p>Many proteins are highly modular, being assembled from globular domains and segments of natively disordered polypeptides. Linear motifs, short sequence modules functioning independently of protein tertiary structure, are most abundant in natively disordered polypeptides but are also found in accessible parts of globular domains, such as exposed loops. The prediction of novel occurrences of known linear motifs attempts the difficult task of distinguishing functional matches from stochastically occurring non-functional matches. Although functionality can only be confirmed experimentally, confidence in a putative motif is increased if a motif exhibits attributes associated with functional instances such as occurrence in the correct taxonomic range, cellular compartment, conservation in homologues and accessibility to interacting partners. Several tools now use these attributes to classify putative motifs based on confidence of functionality.</p> <p>Results</p> <p>Current methods assessing motif accessibility do not consider much of the information available, either predicting accessibility from primary sequence or regarding any motif occurring in a globular region as low confidence. We present a method considering accessibility and secondary structural context derived from experimentally solved protein structures to rectify this situation. Putatively functional motif occurrences are mapped onto a representative domain, given that a high quality reference SCOP domain structure is available for the protein itself or a close relative. Candidate motifs can then be scored for solvent-accessibility and secondary structure context. The scores are calibrated on a benchmark set of experimentally verified motif instances compared with a set of random matches. A combined score yields 3-fold enrichment for functional motifs assigned to high confidence classifications and 2.5-fold enrichment for random motifs assigned to low confidence classifications. The structure filter is implemented as a pipeline with both a graphical interface via the ELM resource <url>http://elm.eu.org/</url> and through a Web Service protocol.</p> <p>Conclusion</p> <p>New occurrences of known linear motifs require experimental validation as the bioinformatics tools currently have limited reliability. The ELM structure filter will aid users assessing candidate motifs presenting in globular structural regions. Most importantly, it will help users to decide whether to expend their valuable time and resources on experimental testing of interesting motif candidates.</p

    Activated Leukocyte Cell Adhesion Molecule Expression and Shedding in Thyroid Tumors

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    Activated leukocyte cell adhesion molecule (ALCAM, CD166) is expressed in various tissues, cancers, and cancer-initiating cells. Alterations in expression of ALCAM have been reported in several human tumors, and cell adhesion functions have been proposed to explain its association with cancer. Here we documented high levels of ALCAM expression in human thyroid tumors and cell lines. Through proteomic characterization of ALCAM expression in the human papillary thyroid carcinoma cell line TPC-1, we identified the presence of a full-length membrane-associated isoform in cell lysate and of soluble ALCAM isoforms in conditioned medium. This finding is consistent with proteolytically shed ALCAM ectodomains. Nonspecific agents, such as phorbol myristate acetate (PMA) or ionomycin, provoked increased ectodomain shedding. Epidermal growth factor receptor stimulation also enhanced ALCAM secretion through an ADAM17/TACE-dependent pathway. ADAM17/TACE was expressed in the TPC-1 cell line, and ADAM17/TACE silencing by specific small interfering RNAs reduced ALCAM shedding. In addition, the CGS27023A inhibitor of ADAM17/TACE function reduced ALCAM release in a dose-dependent manner and inhibited cell migration in a wound-healing assay. We also provide evidence for the existence of novel O-glycosylated forms and of a novel 60-kDa soluble form of ALCAM, which is particularly abundant following cell stimulation by PMA. ALCAM expression in papillary and medullary thyroid cancer specimens and in the surrounding non-tumoral component was studied by western blot and immunohistochemistry, with results demonstrating that tumor cells overexpress ALCAM. These findings strongly suggest the possibility that ALCAM may have an important role in thyroid tumor biology

    An evidence-based framework for predicting the impact of differing autotroph-heterotroph thermal sensitivities on consumer-prey dynamics

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    Increased temperature accelerates vital rates, influencing microbial population and wider ecosystem dynamics, for example, the predicted increases in cyanobacterial blooms associated with global warming. However, heterotrophic and mixotrophic protists, which are dominant grazers of microalgae, may be more thermally sensitive than autotrophs, and thus prey could be suppressed as temperature rises. Theoretical and meta-analyses have begun to address this issue, but an appropriate framework linking experimental data with theory is lacking. Using ecophysiological data to develop a novel model structure, we provide the first validation of this thermal sensitivity hypothesis: increased temperature improves the consumer’s ability to control the autotrophic prey. Specifically, the model accounts for temperature effects on auto- and mixotrophs and ingestion, growth and mortality rates, using an ecologically and economically important system (cyanobacteria grazed by a mixotrophic flagellate). Once established, we show the model to be a good predictor of temperature impacts on consumer–prey dynamics by comparing simulations with microcosm observations. Then, through simulations, we indicate our conclusions remain valid, even with large changes in bottom-up factors (prey growth and carrying capacity). In conclusion, we show that rising temperature could, counterintuitively, reduce the propensity for microalgal blooms to occur and, critically, provide a novel model framework for needed, continued assessment

    Co-infection of cattle with Fasciola hepatica or F. gigantica and Mycobacterium bovis: A systematic review

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    The liver flukes, Fasciola hepatica and F. gigantica, are common trematode parasites of livestock. F. hepatica is known to modulate the immune response, including altering the response to co-infecting pathogens. Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is a chronic disease which is difficult to control and is of both animal welfare and public health concern. Previous research has suggested that infection with liver fluke may affect the accuracy of the bTB skin test, but direction of the effect differs between studies. In a systematic review of the literature, all experimental and observational studies concerning co-infection with these two pathogens were sought. Data were extracted on the association between fluke infection and four measures of bTB diagnosis or pathology, namely, the bTB skin test, interferon γ test, lesion detection and culture/bacterial recovery. Of a large body of literature dating from 1950 to 2019, only thirteen studies met the inclusion criteria. These included studies of experimentally infected calves, case control studies on adult cows, cross sectional abattoir studies and a herd level study. All the studies had a medium or high risk of bias. The balance of evidence from the 13 studies included in the review suggests that liver fluke exposure was associated with either no effect or a decreased response to all of the four aspects of bTB diagnosis assessed: skin test, IFN γ, lesion detection and mycobacteria cultured or recovered. Most studies showed a small and/or non-significant effect so the clinical and practical importance of the observed effect is likely to be modest, although it could be more significant in particular groups of animals, such as dairy cattle
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