Ballardbrewer7856

20 µPa). When thresholds were compared in units of intensity, however, the sensitivity underwater was higher than in air. Eardrum vibration amplitude in both media reflected the ABR threshold curves. These results suggest that cormorants have in-air hearing abilities comparable to those of similar-sized diving birds, and that their underwater hearing sensitivity is at least as good as their aerial sensitivity. This, together with the morphology of the outer ear (collapsible meatus) and middle ear (thickened eardrum), suggests that cormorants may have anatomical and physiological adaptations for amphibious hearing. © 2020. Published by The Company of Biologists Ltd.In cohort splitting diverging sub-cohorts may show substantial differences in their growth and developmental rates. Although in the past causes and adaptive value of cohort splitting were studied in detail, individual-level consequences of cohort splitting are still rather overlooked. Life history theory predicts that considerably increased growth and developmental rates should be traded off against other costly life history traits. However, it is not clear whether one should expect such associations in adaptive developmental plasticity scenarios, because natural selection might have promoted genotypes that mitigate those potential costs of rapid development. To address these contrasting propositions, we assessed life history traits in the wolf spider Pardosa agrestis, both collected from natural habitat and reared in laboratory. We found that some traits are negatively associated with developmental rates in spiders collected from nature, but these associations were relaxed to a considerable extent in laboratory reared specimens. In general, we observed no consistent trend for the presence of developmental costs, although some results might suggest higher relative fecundity costs in rapidly developing females. Our study provides a detailed approach to the understanding of individual-level consequences of cohort splitting, and to the associations between key life history traits in adaptive developmental plasticity scenarios. © 2020. Published by The Company of Biologists Ltd.Mammals living in aquatic environments load their axial skeletons differently from their terrestrial counterparts. The structure and mechanical behavior of trabecular bone can be especially indicative of varying habitual forces. Here, we investigated vertebral trabecular bone mechanical properties (yield strength, stiffness and toughness) throughout development in Florida manatees (Trichechus manatus latirostris), obligate undulatory swimmers. Thoracic, lumbar and caudal vertebrae were dissected from manatees (N=20) during necropsies. We extracted 6 mm3 samples from vertebral bodies and tested them in compression in three orientations (rostrocaudal, dorsoventral and mediolateral) at 2 mm min-1 We determined variation in mechanical properties between sexes, and among developmental stages, vertebral regions and testing orientations. We also investigated the relationships between vertebral process lengths and properties of dorsoventrally and mediolaterally tested bone. Rostrocaudally tested bone was the strongest, stiffest and toughest, suggesting that this is the principal direction of stress. Our results showed that bone from female subadults was stronger and stiffer than that of their male counterparts; based on these data, we hypothesize that hormonal shifts at sexual maturity may partially drive these differences. In calves, bone from the posterior region was stronger and tougher than that from the anterior region. We hypothesize that as animals grow rapidly throughout early development, bone in the posterior region would be the most ossified to support the rostrocaudal force propagation associated with undulatory swimming. © 2020. Published by The Company of Biologists Ltd.Juvenile striped bass residing in Chesapeake Bay are likely to encounter hypoxia that could affect their metabolism and performance. The ecological success of this economically valuable species may depend on their ability to tolerate hypoxia and perform fitness-dependent activities in hypoxic waters. We tested whether there is a link between hypoxia tolerance (HT) and oxygen consumption rate (Ṁ O2 ) of juvenile striped bass measured while swimming in normoxic and hypoxic water, and to identify the interindividual variation and repeatability of these measurements. HT (loss of equilibrium) of fish (N=18) was measured twice collectively, 11 weeks apart, between which Ṁ O2  was measured individually for each fish while swimming in low flow (10.2 cm s-1) and high flow (∼67% of critical swimming speed, U crit) under normoxia and hypoxia. Both HT and Ṁ O2  varied substantially among individuals. HT increased across 11 weeks while the rank order of individual HT was significantly repeatable. Similarly, Ṁ O2  increased in fish swimming at high flow in a repeatable fashion, but only within a given level of oxygenation. this website Ṁ O2  was significantly lower when fish were swimming against high flow under hypoxia. There were no clear relationships between HT and Ṁ O2  while fish were swimming under any conditions. Only the magnitude of increase in HT over 11 weeks and an individual's Ṁ O2  under low flow were correlated. The results suggest that responses to the interacting stressors of hypoxia and exercise vary among individuals, and that HT and change in HT are not simple functions of aerobic metabolic rate. © 2020. Published by The Company of Biologists Ltd.Myasthenia gravis (MG) is a chronic autoimmune disorder of the neuromuscular junction characterised by an autoantibody against acetylcholine receptor (AChR-Ab), autoantibody against muscle-specific kinase (MuSK-Ab), lipoprotein-related protein 4 or agrin in the postsynaptic membrane at the neuromuscular junction. Many patients are resistant to conventional treatment and effective therapies are needed. Rituximab (RTX) is a monoclonal antibody directed against CD20 antigen on B cells which has been successfully employed in anti-MuSK-Ab+MG, but the efficacy in anti-AChR-Ab+MG is still debated. The purpose of this systematic review was to describe the best evidence for RTX in the acetylcholine receptor subtype. The authors undertook a literature search during the period of 1999-2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analys methodology, employing (myasthenia)+(gravis)+(RTX) as search terms. The analysis was confined to studies that include at least five patients with confirmed anti-AChR-Ab+MG. Thirteen studies have been selected, showing a good safety. The data obtained were heterogeneous in terms of posology, administration scheme and patients' evaluation, ranging from a minimum of two to a maximum of three cycles. RTX led to a sustained clinical improvement with prolonged time to relapse, in parallel to a reduction or discontinuation of other immunosuppressive therapies. link2 Treatment with RTX appears to work in some but not all patients with anti-AChR-Ab+MG, but randomised controlled trials are needed. Future studies should take into account the subtype of MG and employ reliable measures of outcome and severity focusing on how to identify patients who may benefit from the treatment. Trial registration number NCT02110706. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Apolipoprotein A-I (apoA-I) is the major protein constituent of high density lipoprotein (HDL) and a target of myeloperoxidase-dependent oxidation in the artery wall. In atherosclerotic lesions, apoA-I exhibits marked oxidative modifications at multiple sites including tryptophan 72 (Trp72). Site-specific mutagenesis studies have suggested, but not conclusively shown, that oxidative modification of Trp72 of apoA-I impairs many atheroprotective properties of this lipoprotein. Herein, we used genetic code expansion technology with an engineered Saccharomyces cerevisiae tryptophanyl tRNA-synthetase (Trp-RS) suppressor tRNA pair to insert the non-canonical amino acid 5-hydroxytryptophan (5-OHTrp) at position 72 in recombinant human apoA-I, and confirmed site-specific incorporation utilizing mass spectrometry. In functional characterization studies, 5-OHTrp72 apoA-I (compared with wild-type (WT) apoA-I) exhibited reduced ATP binding cassette subfamily A member 1 (ABCA1)-dependent cholesterol acceptor activity in vitro (41.73% ± 6.57% inhibition; P less then 0.01). Additionally, 5-OHTrp72 apoA-I displayed increased activation and stabilization of paraoxonase 1 (PON1) activity (µmoles/min/mg) when compared to WT apoA-I, and comparable PON1 activation/stabilization compared to reconstituted HDL (WT apoA-I, 1.92 ± 0.04; 5-OHTrp72 apoA-I, 2.35 ± 0.0; and HDL, 2.33 ± 0.1; P less then 0.001, P less then 0.001, and P less then 0.001, respectively). Following injection into apoA-I deficient mice, 5-OHTrp72 apoA-I reached plasma levels comparable to those of native apoA-I, yet exhibited significantly reduced (48%; P less then 0.01) lipidation and evidence of HDL biogenesis. Collectively, these findings unequivocally reveal that site-specific oxidative modification of apoA-I via 5-OHTrp at Trp72 impairs cholesterol efflux and the rate-limiting step of HDL biogenesis both in vitro and in vivo. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.The E-protein transcription factors guide immune cell differentiation, with E12 and E47 (hereafter called E2A) being essential for B-cell specification and maturation. E2A and the oncogenic chimera E2A-PBX1 contain three transactivation domains (ADs), with AD1 and AD2 having redundant, independent, and cooperative functions in a cell-dependent manner. AD1 and AD2 both mediate their functions by binding to the KIX domain of the histone acetyltransferase paralogues CREB-binding protein (CBP) and E1A-binding protein P300 (p300). This interaction is necessary for B-cell maturation and oncogenesis by E2A-PBX1 and occurs through conserved ϕ-x-x-ϕ-ϕ motifs (with ϕ denoting a hydrophobic amino acid) in AD1 and AD2. However, disruption of this interaction via mutation of the KIX domain in CBP/p300 does not completely abrogate binding of E2A and E2APBX1. Here, we determined that E2A-AD1 and E2A-AD2 also interact with the TAZ2 domain of CBP/p300. Characterization of the TAZ2E2AAD1(1-37) complex indicated that E2A-AD1 adopts an α-helical structure and uses its ϕ-x-x-ϕ-ϕ motif to bind TAZ2. link3 While this region overlapped with the KIX recognition region, key KIX-interacting E2A-AD1 residues were exposed, suggesting that E2A-AD1 could simultaneously bind both the KIX and TAZ2 domains. However, we did not detect a ternary complex involving E2A-AD1, KIX, and TAZ2 and found that E2A containing both intact AD1 and AD2 is required to bind to CBP/p300. Our findings highlight the structural plasticity and promiscuity of E2A-AD1 and suggest that E2A binds both the TAZ2 and KIX domains of CBP/p300 through AD1 and AD2. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.The Escherichia coli outer membrane receptor FepA transports ferric enterobactin (FeEnt) by an energy- and TonB-dependent, but otherwise mechanistically undetermined process involving its internal, 150-residue N-terminal globular domain (N-domain). We genetically introduced pairs of Cys residues in different regions of FepA tertiary structure, with the potential to form disulfide bonds.  These included Cys-pairs on adjacent β-strands of the N-domain (intra - N), and Cys-pairs that bridged the external surface of the N-domain to the interior of the C-terminal transmembrane β-barrel (inter - N-C).   We characterized FeEnt uptake by these mutants with siderophore nutrition tests, [59Fe]Ent binding and uptake experiments, and fluorescence decoy (FD) sensor assays.  The three methods consistently showed that the intra - N disulfide bonds, that restrict conformational motion within the N-domain, prevented FeEnt uptake, whereas most inter - N-C disulfide bonds did not prevent FeEnt uptake.  These outcomes indicate that conformational rearrangements must occur in the N-terminus of FepA during FeEnt transport.