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Background: Antiphospholipid syndrome is associated with endothelial dysfunction, which leads to thrombosis and early atheroma. Given that hydroxychloroquine has anti-thrombotic properties in lupus, we hypothesized that it could reduce endothelial dysfunction in an animal model of antiphospholipid syndrome. We evaluated the effect of hydroxychloroquine in preventing endothelial dysfunction in a mouse model of antiphospholipid syndrome. Methods: Antiphospholipid syndrome was induced by an injection of monoclonal anti-beta-2-GPI antibodies. Vascular reactivity was evaluated in mesenteric resistance arteries isolated from mice 3 weeks (APL3W) after receiving a single injection of anti-beta-2-GPI antibodies and after 3 weeks of daily oral hydroxychloroquine treatment (HCQ3W) compared to control mice (CT3W). We evaluated endothelial dysfunction by measuring acetylcholine-mediated vasodilation. A pharmacological approach was used to evaluate NO synthase uncoupling (tetrahydrobiopterin) and the generation of reactive oxygen species (Tempol). Results: Impaired acetylcholine-mediated dilation was evidenced in mice 3 weeks after anti-beta-2-GPI antibodies injection compared to CT3W, by reduced maximal dilation (p<0.0001) and sensitivity (pKd) (p = 0.01) to acetylcholine. Hydroxychloroquine improved acetylcholine-dependent dilation, on pKd (p = 0.02) but not maximal capacity compared to untreated mice. The addition of tetrahydrobiopterin (p = 0.02) and/or Tempol (p = 0.0008) improved acetylcholine-mediated dilation in APL3W but not in HCQ3W. Conclusions: We demonstrated that endothelial dysfunction in mouse resistance arteries persisted at 3 weeks after a single injection of monoclonal anti-beta-2-GPI antibodies, and that hydroxychloroquine improved endothelium-dependent dilation at 3 weeks, through improvement of NO synthase coupling and oxidative stress reduction. [ABSTRACT FROM AUTHOR]

During breeding, foraging marine birds are under biological, geographic, and temporal constraints. These contraints require foraging birds to efficiently process environmental cues derived from physical habitat features that occur at nested spatial scales. Mesoscale oceanography in particular may change rapidly within and between breeding seasons, and findings from well-studied systems that relate oceanography to seabird foraging may transfer poorly to regions with substantially different oceanographic conditions. Our objective was to examine foraging behavior of a pan-tropical seabird, the Masked Booby (Sula dactylatra), in the understudied Caribbean province, a moderately productive region driven by highly dynamic currents and fronts. We tracked 135 individuals with GPS units during May 2013, November 2013, and December 2014 at a regionally important breeding colony in the southern Gulf of Mexico. We measured foraging behavior using characteristics of foraging trips and used area restricted search as a proxy for foraging events. Among individual attributes, nest stage contributed to differences in foraging behavior whereas sex did not. Birds searched for prey at nested hierarchical scales ranging from 200 m—35 km. Large-scale coastal and shelf-slope fronts shifted position between sampling periods and overlapped geographically with overall foraging locations. At small scales (at the prey patch level), the specific relationship between environmental variables and foraging behavior was highly variable among individuals but general patterns emerged. Sea surface height anomaly and velocity of water were the strongest predictors of area restricted search behavior in random forest models, a finding that is consistent with the characterization of the Gulf of Mexico as an energetic system strongly influenced by currents and eddies. Our data may be combined with tracking efforts in the Caribbean province and across tropical regions to advance understanding of seabird sensing of the environment and serve as a baseline for anthropogenic based threats such as development, pollution, and commercial fisheries. [ABSTRACT FROM AUTHOR]

Background: Recent studies have demonstrated the key role of the complement alternative pathway (cAP) in the pathophysiology of experimental ANCA-associated vasculitis (AAV). However, in human AAV the role of cAP has not been extensively explored. In the present work, we analysed circulating serum C3 levels measured at AAV onset and their relation to outcomes. Methods: We conducted a retrospective observational cohort study including 45 consecutive patients with AAV diagnosed between 2000 and 2014 with serum C3 measurement at diagnosis, before immunosuppressive treatment initiation. Two groups were defined according to the median serum C3 level value: the low C3 group (C3<120 mg/dL) and the high C3 level group (C3≥120 mg/dL). Patient and renal survivals, association between C3 level and renal pathology were analysed. Results: Serum complement C3 concentration remained in the normal range [78–184 mg/dL]. Compared with the high C3 level, the patients in the low C3 level group had lower complement C4 concentrations (P = 0.008) and lower eGFR (P = 0.002) at diagnosis. The low C3 level group had poorer patient and death-censored renal survivals, compared with the high C3 level group (P = 0.047 and P = 0.001, respectively). We observed a significant negative correlation between C3 levels and the percentage of glomeruli affected by cellular crescent (P = 0.017, r = -0.407). According to the Berden et al renal histologic classification, patients in the crescentic/mixed category had low C3 levels more frequently (P<0.01). Interestingly, we observed that when patients with the crescentic/mixed histologic form were analysed according to C3 level, long term renal survival was significantly greater in the high C3 level group than in the low C3 level group (100% vs 40.7% at 6 years, p = 0.046). No relationship between serum C4 and renal outcome was observed. Conclusion: A Low C3 serum level in AAV patients at diagnosis is associated with worse long-term patient and renal survival. [ABSTRACT FROM AUTHOR]

In this work, we describe a single piggyBac transposon system containing both a tet-activator and a doxycycline-inducible expression cassette. We demonstrate that a gene product can be conditionally expressed from the integrated transposon and a second gene can be simultaneously targeted by a short hairpin RNA contained within the transposon, both in vivo and in mammalian and avian cell lines. We applied this system to stably modify chicken primordial germ cell (PGC) lines in vitro and induce a reporter gene at specific developmental stages after injection of the transposon-modified germ cells into chicken embryos. We used this vector to express a constitutively-active AKT molecule during PGC migration to the forming gonad. We found that PGC migration was retarded and cells could not colonise the forming gonad. Correct levels of AKT activation are thus essential for germ cell migration during early embryonic development. [ABSTRACT FROM AUTHOR]