21 research outputs found

    Asrij Maintains the Stem Cell Niche and Controls Differentiation during Drosophila Lymph Gland Hematopoiesis

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    Several signaling pathways control blood cell (hemocyte) development in the Drosophila lymph gland. Mechanisms that modulate and integrate these signals are poorly understood. Here we report that mutation in a conserved endocytic protein Asrij affects signal transmission and causes aberrant lymph gland hematopoiesis. Mammalian Asrij (Ociad1) is expressed in stem cells of the blood vascular system and is implicated in several cancers. We found that Drosophila Asrij is a pan-hemocyte marker and localizes to a subset of endocytic vesicles. Loss of asrij causes hyperproliferation of lymph gland lobes coupled with increased hemocyte differentiation, thereby depleting the pool of quiescent hemocyte precursors. This co-relates with fewer Col+ cells in the hematopoietic stem cell niche of asrij mutants. Asrij null mutants also show excess specification of crystal cells that express the RUNX factor Lozenge (Lz), a target of Notch signaling. Asrij mutant lymph glands show increased N in sorting endosomes suggesting aberrant trafficking. In vitro assays also show impaired traffic of fluorescent probes in asrij null hemocytes. Taken together our data suggest a role for Asrij in causing increased Notch signaling thereby affecting hemocyte differentiation. Thus, conserved endocytic functions may control blood cell progenitor quiescence and differentiation

    The Dynamic Characteristics of a non-linear main landing gear system of an aircraft during landing

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    The landing gear plays a very important role during landing by absorbing the high impact energy of the aircraft. The main landing gear absorbs the bulk of the load to reduce the load experienced by both the aircraft fuselage and the nose landing gear. In this paper, a mathematical approach is used to extract the dynamic characteristics of the system. A two-degree of freedom mathematical model of the main landing gear is developed. This model is used to derive the dynamic equations of the landing gear system and to study the behaviour of main landing gear during main gear and nose gear touchdown conditions. The non-linear stiffness and damping co-efficient in an Oleo-Pneumatic shock absorber are integrated into the system to achieve a more accurate response of the system. The response of this system is established by adopting a complex modal analysis approach to account for the non-classical damping exhibited by the system. The obtained spring force, damping force and responses are reported. This work provides an alternative approach using complex modal analysis to obtain results for complex systems exhibiting non-linear characteristics

    Clearance of variant Creutzfeldt-Jakob disease prions in vivo by the Hsp70 disaggregase system.

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    The metazoan Hsp70 disaggregase protects neurons from proteotoxicity that arises from the accumulation of misfolded protein aggregates. Hsp70 and its co-chaperones disassemble and extract polypeptides from protein aggregates for refolding or degradation. The effectiveness of the chaperone system decreases with age and leads to accumulation rather than removal of neurotoxic protein aggregates. Therapeutic enhancement of the Hsp70 protein disassembly machinery is proposed to counter late-onset protein misfolding neurodegenerative disease that may arise. In the context of prion disease, it is not known whether stimulation of protein aggregate disassembly paradoxically leads to enhanced formation of seeding competent species of disease-specific proteins and acceleration of neurodegenerative disease. Here we have tested the hypothesis that modulation of Hsp70 disaggregase activity perturbs mammalian prion-induced neurotoxicity and prion seeding activity. To do so we used prion protein (PrP) transgenic Drosophila that authentically replicate mammalian prions. RNASeq identified that Hsp70, DnaJ-1 and Hsp110 gene expression was downregulated in prion-exposed PrP Drosophila. We demonstrated that RNAi knockdown of Hsp110 or DnaJ-1 gene expression in variant Creutzfeldt-Jakob disease prion-exposed human PrP Drosophila enhanced neurotoxicity, whereas overexpression mitigated toxicity. Strikingly, prion seeding activity in variant Creutzfeldt-Jakob disease prion-exposed human PrP Drosophila was ablated or reduced by Hsp110 or DnaJ-1 overexpression, respectively. Similar effects were seen in scrapie prion-exposed ovine PrP Drosophila with modified Hsp110 or DnaJ-1 gene expression. These unique observations show that the metazoan Hsp70 disaggregase facilitates the clearance of mammalian prions and that its enhanced activity is a potential therapeutic strategy for human prion disease

    Large anthropogenic impacts on a charismatic small carnivore: Insights from distribution surveys of red panda <i>Ailurus fulgens</i> in Nepal

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    <div><p>Protected areas are key to preserving biodiversity and maintaining ecosystem services. However, their ability to ensure long-term survival of threatened andendangered species varies across countries, regions and landscapes. Distribution surveys can beparticularly important for assessing the value of protected areas, and gauging their efficacy incatering to species-specific requirements. We assessed the conservation value of one such reserve for a charismatic yet globally endangered species, the red panda <i>Ailurus fulgens</i>,in the light of on-going land-use transformation in Nepal. We conducted field surveys forindirect signs of red pandas along forest trails in 25-km<sup>2</sup> sampling grid cells (n = 54) of Dhorpatan Hunting Reserve, and confronted a set of ecological hypotheses to the data using hierarchical occupancy models. We estimated overall occupancy at Ψ(SE) = 0.41 (0.007), with relatively high site-level detectability [<i>p</i> = 0.93 (SE = 0.001)]. Our results show that despitebeing a subsistence form of small-scale resource use, extraction of bamboo and livestock grazing negatively affected panda occurrence, albeit at different intensities. The amount of bamboo cover,rather than the overall proportion of forest cover, had greater influence on the panda occurrence. Despite availability of bamboo cover, areas with bamboo extraction and anthropogenic disturbances were less likely to be occupied by pandas. Together, these results suggest that long-term persistence of red pandas in this reserve and elsewhere across the species’ range will require preventing commercial extractionof bamboo, coupled with case-specific regulation of anthropogenic exploitation of red panda habitats.</p></div

    Assessment of Detection Methods and Vegetation Associations for Introduced Finlayson’s Squirrels (Callosciurus finlaysonii) in Italy

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    Managing biological invasions requires rapid, cost-effective assessments of introduced species’ occurrence, and a good understanding of the species’ vegetation associations. This is particularly true for species that are elusive or may spread rapidly. Finlayson’s squirrel (Callosciurus finlaysonii) is native to Thailand and southeastern Asia, and two introduced populations occur in peninsular Italy. One of the two introduced populations is rapidly expanding, but neither effective monitoring protocols nor reliable information on vegetation associations are available. To fill this gap, we conducted visual surveys and hair tube sampling in a periurban landscape of southern Italy to compare the effectiveness of these two methods in assessing presence of Finlayson’s squirrel. We also determined the species’ association with vegetation types at detection locations and nesting sites. Both visual and hair tube sampling effectively assessed the species’ presence, but hair tubes resulted in fewer false absences. Moreover, when we controlled for the costs of labor and equipment, hair tubes were 33.1% less expensive than visual sampling. Presence of squirrels and their nests was positively correlated with shrub species richness, indicating that the occurrence of forests with well-developed understory may inhibit the spread of the species
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