401 research outputs found

    Seasonal variation in daily patterns of social contacts in the European badger Meles meles

    Get PDF
    This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Social interactions among hosts influence the persistence and spread of infectious pathogens. Daily 20 and seasonal variation in the frequency and type of social interactions will play an important role in 21 disease epidemiology, and alongside other factors may have an influence on wider disease dynamics 22 by causing seasonal forcing of infection, especially if the seasonal variation experienced by a 23 population is considerable. We explored temporal variation in within-group contacts in a high-24 density population of European badgers Meles meles naturally-infected with bovine tuberculosis. 25 Summer contacts were more likely and of longer duration during the daytime, while the frequency 26 and duration of winter contacts did not differ between day and night. In spring and autumn within-27 group contacts peaked at dawn and dusk, corresponding with when they were of shortest duration 28 with reduced potential for aerosol transmission of pathogens. Summer and winter could be critical 29 for bovine tuberculosis transmission in badgers, due to the high frequency and duration of contacts 30 during resting periods, and we discuss the links between this result and empirical data. This study 31 reveals clear seasonality in daily patterns of contact frequency and duration in species living in stable 32 social groups, suggesting that changes in social contacts could drive seasonal forcing of infection in 33 wildlife populations even when the number of individuals interacting remains similar.MJS is funded by NERC grant NE/M004546/1 awarded to RAM, DPC, DJH and MB, with RJD and the 386 APHA team at Woodchester Park, UK as project partners. Data were collected for NW’s PhD, funded 387 by Defra. We thank Jared Wilson-Aggarwal and two anonymous reviewers for useful comments and 388 Keith Silk for providing the photograph for Figure 1

    Entorhinal Denervation Induces Homeostatic Synaptic Scaling of Excitatory Postsynapses of Dentate Granule Cells in Mouse Organotypic Slice Cultures

    Get PDF
    Denervation-induced changes in excitatory synaptic strength were studied following entorhinal deafferentation of hippocampal granule cells in mature (β‰₯3 weeks old) mouse organotypic entorhino-hippocampal slice cultures. Whole-cell patch-clamp recordings revealed an increase in excitatory synaptic strength in response to denervation during the first week after denervation. By the end of the second week synaptic strength had returned to baseline. Because these adaptations occurred in response to the loss of excitatory afferents, they appeared to be in line with a homeostatic adjustment of excitatory synaptic strength. To test whether denervation-induced changes in synaptic strength exploit similar mechanisms as homeostatic synaptic scaling following pharmacological activity blockade, we treated denervated cultures at 2 days post lesion for 2 days with tetrodotoxin. In these cultures, the effects of denervation and activity blockade were not additive, suggesting that similar mechanisms are involved. Finally, we investigated whether entorhinal denervation, which removes afferents from the distal dendrites of granule cells while leaving the associational afferents to the proximal dendrites of granule cells intact, results in a global or a local up-scaling of granule cell synapses. By using computational modeling and local electrical stimulations in Strontium (Sr2+)-containing bath solution, we found evidence for a lamina-specific increase in excitatory synaptic strength in the denervated outer molecular layer at 3–4 days post lesion. Taken together, our data show that entorhinal denervation results in homeostatic functional changes of excitatory postsynapses of denervated dentate granule cells in vitro

    Single Collateral Reconstructions Reveal Distinct Phases of Corticospinal Remodeling after Spinal Cord Injury

    Get PDF
    Injuries to the spinal cord often result in severe functional deficits that, in case of incomplete injuries, can be partially compensated by axonal remodeling. The corticospinal tract (CST), for example, responds to a thoracic transection with the formation of an intraspinal detour circuit. The key step for the formation of the detour circuit is the sprouting of new CST collaterals in the cervical spinal cord that contact local interneurons. How individual collaterals are formed and refined over time is incompletely understood

    Antennal sensilla of two female anopheline sibling species with differing host ranges

    Get PDF
    BACKGROUND: Volatile odors are important sensory inputs that shape the behaviour of insects, including agricultural pests and disease vectors. Anopheles gambiae s.s. is a highly anthropophilic mosquito and is the major vector for human malaria in sub-Sahara Africa, while Anopheles quadriannulatus, largely due to its zoophilic behaviour, is considered a non-vector species in the same region. Careful studies of olfaction in these sibling species may lead to insights about the mechanisms that drive host preference behaviour. In the present study, the external anatomy of the antenna, the principle olfactory organ in the female mosquito of both species, was examined as an initial step toward more detailed comparisons. METHODS: Scanning electron and light microscopy were used to examine the antennae ultrastructures of adult female An. gambiae s.s. and An. quadriannulatus. Sensory structures, called sensilla, were categorized and counted; their distributions are reported here as well as densities calculated for each species. RESULTS: Both An. gambiae s.s. and An. quadriannulatus bear five classes of sensilla on their antennae: chaetica (bristles), trichodea (hairs), basiconica (pegs), coeloconica (pitted pegs), and ampullacea (pegs in tubes). Female An. quadriannulatus antennae have approximately one-third more sensilla, and a proportionally larger surface area, than female An. gambiae s.s. antennae. CONCLUSION: The same types of sensilla are found on the antennae of both species. While An. quadriannulatus has greater numbers of each sensilla type, sensilla densities are very similar for each species, suggesting that other factors may be more important to such olfactory-driven behaviours as host preference

    Home: The place the older adult can not imagine living without

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Rapidly aging populations with an increased desire to remain at home and changes in health policy that promote the transfer of health care from formal places, as hospitals and institutions, to the more informal setting of one's home support the need for further research that is designed specifically to understand the experience of home among older adults. Yet, little is known among health care providers about the older adult's experience of home. The aim of this study was to understand the experience of home as experienced by older adults living in a rural community in Sweden.</p> <p>Methods</p> <p>Hermeneutical interpretation, as developed by von Post and Eriksson and based on Gadamer's philosophical hermeneutics, was used to interpret interviews with six older adults. The interpretation included a self examination of the researcher's experiences and prejudices and proceeded through several readings which integrated the text with the reader, allowed new questions to emerge, fused the horizons, summarized main and sub-themes and allowed a new understanding to emerge.</p> <p>Results</p> <p>Two main and six sub-themes emerged. Home was experienced as the place the older adult could not imagine living without but also as the place one might be forced to leave. The older adult's thoughts vacillated between the well known present and all its comforts and the unknown future with all its questions and fears, including the underlying threat of loosing one's home.</p> <p>Conclusions</p> <p>Home has become so integral to life itself and such an intimate part of the older adult's being that when older adults lose their home, they also loose the place closest to their heart, the place where they are at home and can maintain their identity, integrity and way of living. Additional effort needs to be made to understand the older adult's experience of home within home health care in order to minimize intrusion and maximize care. There is a need to more fully explore the older adult's experience with health care providers in the home and its impact on the older adult's sense of "being at home" and their health and overall well-being.</p

    Post-Training Dephosphorylation of eEF-2 Promotes Protein Synthesis for Memory Consolidation

    Get PDF
    Memory consolidation, which converts acquired information into long-term storage, is new protein synthesis-dependent. As protein synthesis is a dynamic process that is under the control of multiple translational mechanisms, however, it is still elusive how these mechanisms are recruited in response to learning for memory consolidation. Here we found that eukaryotic elongation factor-2 (eEF-2) was dramatically dephosphorylated within 0.5–2 hr in the hippocampus and amygdala of mice following training in a fear-conditioning test, whereas genome-wide microarrays did not reveal any significant change in the expression level of the mRNAs for translational machineries or their related molecules. Moreover, blockade of NMDA receptors with MK-801 immediately following the training significantly impeded both the post-training eEF-2 dephosphorylation and memory retention. Notably, with an elegant sophisticated transgenic strategy, we demonstrated that hippocampus-specific overexpression of eEF-2 kinase, a kinase that specifically phosphorylates and hence inactivates eEF-2, significantly inhibited protein synthesis in the hippocampus, and this effects was more robust during an β€œongoing” protein synthesis process. As a result, late phase long-term potentiation (L-LTP) in the hippocampus and long-term hippocampus-dependent memory in the mice were significantly impaired, whereas short-term memory and long-term hippocampus-independent memory remained intact. These results reveal a novel translational underpinning for protein synthesis pertinent to memory consolidation in the mammalian brain

    Nitrogenase Gene Amplicons from Global Marine Surface Waters Are Dominated by Genes of Non-Cyanobacteria

    Get PDF
    Cyanobacteria are thought to be the main N2-fixing organisms (diazotrophs) in marine pelagic waters, but recent molecular analyses indicate that non-cyanobacterial diazotrophs are also present and active. Existing data are, however, restricted geographically and by limited sequencing depths. Our analysis of 79,090 nitrogenase (nifH) PCR amplicons encoding 7,468 unique proteins from surface samples (ten DNA samples and two RNA samples) collected at ten marine locations world-wide provides the first in-depth survey of a functional bacterial gene and yield insights into the composition and diversity of the nifH gene pool in marine waters. Great divergence in nifH composition was observed between sites. Cyanobacteria-like genes were most frequent among amplicons from the warmest waters, but overall the data set was dominated by nifH sequences most closely related to non-cyanobacteria. Clusters related to Alpha-, Beta-, Gamma-, and Delta-Proteobacteria were most common and showed distinct geographic distributions. Sequences related to anaerobic bacteria (nifH Cluster III) were generally rare, but preponderant in cold waters, especially in the Arctic. Although the two transcript samples were dominated by unicellular cyanobacteria, 42% of the identified non-cyanobacterial nifH clusters from the corresponding DNA samples were also detected in cDNA. The study indicates that non-cyanobacteria account for a substantial part of the nifH gene pool in marine surface waters and that these genes are at least occasionally expressed. The contribution of non-cyanobacterial diazotrophs to the global N2 fixation budget cannot be inferred from sequence data alone, but the prevalence of non-cyanobacterial nifH genes and transcripts suggest that these bacteria are ecologically significant

    A Unified Model of the GABA(A) Receptor Comprising Agonist and Benzodiazepine Binding Sites

    Get PDF
    We present a full-length Ξ±(1)Ξ²(2)Ξ³(2) GABA receptor model optimized for agonists and benzodiazepine (BZD) allosteric modulators. We propose binding hypotheses for the agonists GABA, muscimol and THIP and for the allosteric modulator diazepam (DZP). The receptor model is primarily based on the glutamate-gated chloride channel (GluCl) from C. elegans and includes additional structural information from the prokaryotic ligand-gated ion channel ELIC in a few regions. Available mutational data of the binding sites are well explained by the model and the proposed ligand binding poses. We suggest a GABA binding mode similar to the binding mode of glutamate in the GluCl X-ray structure. Key interactions are predicted with residues Ξ±(1)R66, Ξ²(2)T202, Ξ±(1)T129, Ξ²(2)E155, Ξ²(2)Y205 and the backbone of Ξ²(2)S156. Muscimol is predicted to bind similarly, however, with minor differences rationalized with quantum mechanical energy calculations. Muscimol key interactions are predicted to be Ξ±(1)R66, Ξ²(2)T202, Ξ±(1)T129, Ξ²(2)E155, Ξ²(2)Y205 and Ξ²(2)F200. Furthermore, we argue that a water molecule could mediate further interactions between muscimol and the backbone of Ξ²(2)S156 and Ξ²(2)Y157. DZP is predicted to bind with interactions comparable to those of the agonists in the orthosteric site. The carbonyl group of DZP is predicted to interact with two threonines Ξ±(1)T206 and Ξ³(2)T142, similar to the acidic moiety of GABA. The chlorine atom of DZP is placed near the important Ξ±(1)H101 and the N-methyl group near Ξ±(1)Y159, Ξ±(1)T206, and Ξ±(1)Y209. We present a binding mode of DZP in which the pending phenyl moiety of DZP is buried in the binding pocket and thus shielded from solvent exposure. Our full length GABA(A) receptor is made available as Model S1

    The Secrets of a Functional Synapse – From a Computational and Experimental Viewpoint

    Get PDF
    BACKGROUND: Neuronal communication is tightly regulated in time and in space. The neuronal transmission takes place in the nerve terminal, at a specialized structure called the synapse. Following neuronal activation, an electrical signal triggers neurotransmitter (NT) release at the active zone. The process starts by the signal reaching the synapse followed by a fusion of the synaptic vesicle and diffusion of the released NT in the synaptic cleft; the NT then binds to the appropriate receptor, and as a result, a potential change at the target cell membrane is induced. The entire process lasts for only a fraction of a millisecond. An essential property of the synapse is its capacity to undergo biochemical and morphological changes, a phenomenon that is referred to as synaptic plasticity. RESULTS: In this survey, we consider the mammalian brain synapse as our model. We take a cell biological and a molecular perspective to present fundamental properties of the synapse:(i) the accurate and efficient delivery of organelles and material to and from the synapse; (ii) the coordination of gene expression that underlies a particular NT phenotype; (iii) the induction of local protein expression in a subset of stimulated synapses. We describe the computational facet and the formulation of the problem for each of these topics. CONCLUSION: Predicting the behavior of a synapse under changing conditions must incorporate genomics and proteomics information with new approaches in computational biology
    • …
    corecore