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981.
982.
Luqiao?Wang Hangfei?Fu Gayani?Nanayakkara Yafeng?Li Ying?Shao Candice?Johnson Jiali?Cheng William?Y.?Yang Fan?Yang Muriel?Lavallee Yanjie?Xu Xiaoshu?Cheng Hang?Xi Jonathan?Yi Jun?Yu Eric?T.?Choi Hong?Wang Xiaofeng?Yang
Background
Caspase-1 is present in the cytosol as an inactive zymogen and requires the protein complexes named “inflammasomes” for proteolytic activation. However, it remains unclear whether the proteolytic activity of caspase-1 is confined only to the cytosol where inflammasomes are assembled to convert inactive pro-caspase-1 to active caspase-1.Methods
We conducted meticulous data analysis method?s on proteomic, protein interaction, protein intracellular localization, and gene expressions of 114 experimentally identified caspase-1 substrates and 38 caspase-1 interaction proteins in normal physiological conditions and in various pathologies.Results
We made the following important findings: (1) Caspase-1 substrates and interaction proteins are localized in various intracellular organelles including nucleus and secreted extracellularly; (2) Caspase-1 may get activated in situ in the nucleus in response to intra-nuclear danger signals; (3) Caspase-1 cleaves its substrates in exocytotic secretory pathways including exosomes to propagate inflammation to neighboring and remote cells; (4) Most of caspase-1 substrates are upregulated in coronary artery disease regardless of their subcellular localization but the majority of metabolic diseases cause no significant expression changes in caspase-1 nuclear substrates; and (5) In coronary artery disease, majority of upregulated caspase-1 extracellular substrate-related pathways are involved in induction of inflammation; and in contrast, upregulated caspase-1 nuclear substrate-related pathways are more involved in regulating cell death and chromatin regulation.Conclusions
Our identification of novel caspase-1 trafficking sites, nuclear and extracellular inflammasomes, and extracellular caspase-1-based inflammation propagation model provides a list of targets for the future development of new therapeutics to treat cardiovascular diseases, inflammatory diseases, and inflammatory cancers.983.
The effect of close approaches for tagging activities by small research vessels on the behavior of humpback whales (Megaptera novaeangliae) 下载免费PDF全文
Michael J. Williamson Ailbhe S. Kavanagh Michael J. Noad Eric Kniest Rebecca A. Dunlop 《Marine Mammal Science》2016,32(4):1234-1253
Small research vessels are often used as platforms for tagging activities to collect behavioral data on cetaceans and they have the potential to disturb that group or individual. If this disturbance is ignored, results and conclusions produced by that study could be inaccurate. Here land‐based behavioral data of migrating humpback whales (Megaptera novaeangliae) (n = 29) were used to determine the effect of close approaches for tagging by research vessels on their diving, movement and surface behaviors. Groups of whales were tagged, using digital recording tags, by small research vessels, as part of a behavioral response study. In groups that were approached for tagging, temporary changes in movement behaviors during close approaches were found, with subsequent recovery to “pre‐approach” levels. In female‐calf groups more long‐term changes in travel speed were found. Results suggest that, although close approaches for tagging by small vessels may cause behavioral changes in humpback whales, this change may be small and temporary. However, in female‐calf groups, the behavioral change may be greater and longer lasting. This study shows that when using small vessels for behavioral research, disturbance, and recovery should be measured to ensure integrity of data used for other analyses. 相似文献
984.
985.
Chao-Hsuan Chang Ying-Chun Chen Weici Zhang Patrick S. C. Leung M. Eric Gershwin Ya-Hui Chuang 《PloS one》2015,10(3)
Invariant natural killer T (iNKT) cells play complex roles in bridging innate and adaptive immunity by engaging with glycolipid antigens presented by CD1d. Our earlier work suggested that iNKT cells were involved in the initiation of the original loss of tolerance in primary biliary cirrhosis (PBC). To address this issue in more detail and, in particular, to focus on whether iNKT cells activated by a Th2-biasing agonist (2s,3s,4r)-1-O-(α-D-galactopyranosyl)-N-tetracosanoyl-2-amino-1,3,4-nonanetriol (OCH), can influence the development of PBC in a xenobiotic-induced PBC murine model. Groups of mice were treated with either OCH or, as a control, α-galactosylceramide (α-GalCer) and thence serially followed for cytokine production, markers of T cell activation, liver histopathology and anti-mitochondrial antibody responses. Further, additional groups of CD1d deleted mice were similarly studied. Our data indicate that administration of OCH has a dramatic influence with exacerbation of portal inflammation and hepatic fibrosis similar to mice treated with α-GalCer. Further, iNKT cell deficient CD1d knockout mice have decreased inflammatory portal cell infiltrates and reduced anti-mitochondrial antibody responses. We submit that activation of iNKT cells can occur via overlapping and/or promiscuous pathways and highlight the critical role of innate immunity in the natural history of autoimmune cholangitis. These data have implications for humans with PBC and emphasize that therapeutic strategies must focus not only on suppressing adaptive responses, but also innate immunity. 相似文献
986.
Climate‐driven changes to the spatio‐temporal distribution of the parasitic nematode,Haemonchus contortus,in sheep in Europe 下载免费PDF全文
Hannah Rose Cyril Caminade Muhammad Bashir Bolajoko Paul Phelan Jan van Dijk Matthew Baylis Diana Williams Eric R. Morgan 《Global Change Biology》2016,22(3):1271-1285
Recent climate change has resulted in changes to the phenology and distribution of invertebrates worldwide. Where invertebrates are associated with disease, climate variability and changes in climate may also affect the spatio‐temporal dynamics of disease. Due to its significant impact on sheep production and welfare, the recent increase in diagnoses of ovine haemonchosis caused by the nematode Haemonchus contortus in some temperate regions is particularly concerning. This study is the first to evaluate the impact of climate change on H. contortus at a continental scale. A model of the basic reproductive quotient of macroparasites, Q0, adapted to H. contortus and extended to incorporate environmental stochasticity and parasite behaviour, was used to simulate Pan‐European spatio‐temporal changes in H. contortus infection pressure under scenarios of climate change. Baseline Q0 simulations, using historic climate observations, reflected the current distribution of H. contortus in Europe. In northern Europe, the distribution of H. contortus is currently limited by temperatures falling below the development threshold during the winter months and within‐host arrested development is necessary for population persistence over winter. In southern Europe, H. contortus infection pressure is limited during the summer months by increased temperature and decreased moisture. Compared with this baseline, Q0 simulations driven by a climate model ensemble predicted an increase in H. contortus infection pressure by the 2080s. In northern Europe, a temporal range expansion was predicted as the mean period of transmission increased by 2–3 months. A bimodal seasonal pattern of infection pressure, similar to that currently observed in southern Europe, emerges in northern Europe due to increasing summer temperatures and decreasing moisture. The predicted patterns of change could alter the epidemiology of H. contortus in Europe, affect the future sustainability of contemporary control strategies, and potentially drive local adaptation to climate change in parasite populations. 相似文献
987.
Intermediate habitat associations by hybrids may facilitate genetic introgression in a songbird 下载免费PDF全文
Eric M. Wood Sara E. Barker Swarthout Wesley M. Hochachka Jeffery L. Larkin Ronald W. Rohrbaugh Kenneth V. Rosenberg Amanda D. Rodewald 《Journal of avian biology》2016,47(4):508-520
Hybridization or the interbreeding of genetically discrete populations or species can occur where ranges of genetically distinct units overlap. Golden‐winged warblers Vermivora chrysoptera, a species that has been in steady decline for decades, highlight the potential population‐level consequences of hybridization. A major factor implicated in their decline is hybridization with their sister species, the blue‐winged warbler Vermivora cyanoptera, which has likely been exacerbated by historic and current land‐use practices. We examined habitat associations of golden‐winged and blue‐winged warblers, phenotypic hybrids, and cryptic hybrids (i.e. mismatch between plumage phenotype and genotype as identified by mitochondrial DNA) in an area of relatively recent range overlap and hybridization in northern New York, USA. To explore the robustness of these results, we then compared the patterns from New York with habitat associations from the central Pennsylvanian Appalachian Mountains where blue‐winged warblers either do not occur or are in very low abundance, yet cryptic golden‐winged warbler hybrids are present. From 2008 to 2011, we captured 122 birds in New York and 28 in Pennsylvania and collected blood samples, which we used to determine maternal ancestry. For each bird captured, we measured territory‐level (50‐m radius circles) habitat, and later used remote‐sensing data to quantify habitat on the territories and in surrounding areas (100‐, 250‐, and 500‐m radius circles). In New York, golden‐winged warblers occupied structurally heterogeneous territories surrounded by homogeneously structured, contiguous deciduous forest, far from urban areas. Blue‐winged warblers showed opposite associations, and hybrids’ habitat associations were typically intermediate. In Pennsylvania, the habitat associations of golden‐winged warblers and their cryptic hybrids were remarkably similar to those in New York. These findings suggest that patterns of habitat occupancy by hybrids may promote contact with golden‐winged warblers and thus likely facilitate genetic introgression, even in areas where the parental species are not sympatric. 相似文献
988.
Paula M. Nogueira Rafael R. Assis Ana C. Torrecilhas Elvira M. Saraiva Natália L. Pessoa Marco A. Campos Eric F. Marialva Cláudia M. Ríos-Velasquez Felipe A. Pessoa Nágila F. Secundino Jer?nimo N. Rugani Elsa Nieves Salvatore J. Turco Maria N. Melo Rodrigo P. Soares 《PLoS neglected tropical diseases》2016,10(8)
The immunomodulatory properties of lipophosphoglycans (LPG) from New World species of Leishmania have been assessed in Leishmania infantum and Leishmania braziliensis, the causative agents of visceral and cutaneous leishmaniasis, respectively. This glycoconjugate is highly polymorphic among species with variation in sugars that branch off the conserved Gal(β1,4)Man(α1)-PO4 backbone of repeat units. Here, the immunomodulatory activity of LPGs from Leishmania amazonensis, the causative agent of diffuse cutaneous leishmaniasis, was evaluated in two strains from Brazil. One strain (PH8) was originally isolated from the sand fly and the other (Josefa) was isolated from a human case. The ability of purified LPGs from both strains was investigated during in vitro interaction with peritoneal murine macrophages and CHO cells and in vivo infection with Lutzomyia migonei. In peritoneal murine macrophages, the LPGs from both strains activated TLR4. Both LPGs equally activate MAPKs and the NF-κB inhibitor p-IκBα, but were not able to translocate NF-κB. In vivo experiments with sand flies showed that both stains were able to sustain infection in L. migonei. A preliminary biochemical analysis indicates intraspecies variation in the LPG sugar moieties. However, they did not result in different activation profiles of the innate immune system. Also those polymorphisms did not affect infectivity to the sand fly. 相似文献
989.
Erwan Lagadec Yann Gomard Gildas Le Minter Colette Cordonin Eric Cardinale Beza Ramasindrazana Muriel Dietrich Steven M Goodman Pablo Tortosa Koussay Dellagi 《PLoS neglected tropical diseases》2016,10(8)
Leptospirosis is a bacterial zoonosis of major concern on tropical islands. Human populations on western Indian Ocean islands are strongly affected by the disease although each archipelago shows contrasting epidemiology. For instance, Mayotte, part of the Comoros Archipelago, differs from the other neighbouring islands by a high diversity of Leptospira species infecting humans that includes Leptospira mayottensis, a species thought to be unique to this island. Using bacterial culture, molecular detection and typing, the present study explored the wild and domestic local mammalian fauna for renal carriage of leptospires and addressed the genetic relationships of the infecting strains with local isolates obtained from acute human cases and with Leptospira strains hosted by mammal species endemic to nearby Madagascar. Tenrec (Tenrec ecaudatus, Family Tenrecidae), a terrestrial mammal introduced from Madagascar, is identified as a reservoir of L. mayottensis. All isolated L. mayottensis sequence types form a monophyletic clade that includes Leptospira strains infecting humans and tenrecs on Mayotte, as well as two other Malagasy endemic tenrecid species of the genus Microgale. The lower diversity of L. mayottensis in tenrecs from Mayotte, compared to that occurring in Madagascar, suggests that L. mayottensis has indeed a Malagasy origin. This study also showed that introduced rats (Rattus rattus) and dogs are probably the main reservoirs of Leptospira borgpetersenii and Leptospira kirschneri, both bacteria being prevalent in local clinical cases. Data emphasize the epidemiological link between the two neighbouring islands and the role of introduced small mammals in shaping the local epidemiology of leptospirosis. 相似文献
990.
Intravascular magnetomotive optical coherence tomography of targeted early‐stage atherosclerotic changes in ex vivo hyperlipidemic rabbit aortas 下载免费PDF全文
Jongsik Kim Adeel Ahmad Joanne Li Marina Marjanovic Eric J. Chaney Kenneth S. Suslick Stephen A. Boppart 《Journal of biophotonics》2016,9(1-2):109-116
We report the development of an intravascular magnetomotive optical coherence tomography (IV‐MM‐OCT) system used with targeted protein microspheres to detect early‐stage atherosclerotic fatty streaks/plaques. Magnetic microspheres (MSs) were injected in vivo in rabbits, and after 30 minutes of in vivo circulation, excised ex vivo rabbit aorta samples specimens were then imaged ex vivo with our prototype IV‐MM‐OCT system. The alternating magnetic field gradient was provided by a unique pair of external custom‐built electromagnetic coils that modulated the targeted magnetic MSs. The results showed a statistically significant MM‐OCT signal from the aorta samples specimens injected with targeted MSs.