Quaternary structure of the European spiny lobster (Palinurus elephas) 1 x 6-mer hemocyanin from cryoEM and amino acid sequence data

Arthropod hemocyanins are large respiratory proteins that are composed of up to 48 subunits (8 x 6-mer) in the 75 kDa range. A 3D reconstruction of the 1 x 6-mer hemocyanin from the European spiny lobster Palinuris elephas has been performed from 9970 single particles using cryoelectron microscopy. An 8 Angstrom resolution of the hemocyanin 3D reconstruction has been obtained from about 600 final class averages. Visualisation of structural elements such as a-helices has been achieved. An amino acid sequence alignment shows the high sequence identity (>80%.) of the hemocyanin subunits from the European spiny lobster P. elephas and the American spiny lobster Panulirus interruptus. Comparison of the P. elephas hemocyanin electron microscopy (EM) density map with the known P. interruptus X-ray structure shows a close structural correlation, demonstrating the reliability of both methods for reconstructing proteins, By molecular modelling, we have found the putative locations for the amino acid sequence (597-605) and the C-terminal end (654-657), which are absent in the available P. interruptus X-ray data. (C) 2002 Elsevier Science Ltd. All rights reserve

Reliability of team-based self-monitoring in critical events: A pilot study

Background: Teamwork is a critical component during critical events. Assessment is mandatory for remediation and to target training programmes for observed performance gaps. Methods: The primary purpose was to test the feasibility of team-based self-monitoring of crisis resource management with a validated teamwork assessment tool. A secondary purpose was to assess item-specific reliability and content validity in order to develop a modified context-optimised assessment tool.We conducted a prospective, single-centre study to assess team-based self-monitoring of teamwork after in-situ inter-professional simulated critical events by comparison with an assessment by observers. The Mayo High Performance Teamwork Scale (MHPTS) was used as the assessment tool with evaluation of internal consistency, item-specific consensus estimates for agreement between participating teams and observers, and content validity. Results: 105 participants and 58 observers completed the MHPTS after a total of 16 simulated critical events over 8 months. Summative internal consistency of the MHPTS calculated as Cronbachs alpha was acceptable with 0.712 for observers and 0.710 for participants. Overall consensus estimates for dichotomous data (agreement/non-agreement) was 0.62 (Cohens kappa; IQ-range 0.31-0.87). 6/16 items had excellent (kappa > 0.8) and 3/16 good reliability (kappa > 0.6). Short questions concerning easy to observe behaviours were more likely to be reliable. The MHPTS was modified using a threshold for good reliability of kappa > 0.6. The result is a 9 item self-assessment tool (TeamMonitor) with a calculated median kappa of 0.86 (IQ-range: 0.67-1.0) and good content validity.Conclusions: Team-based self-monitoring with the MHPTS to assess team performance during simulated critical events is feasible. A context-based modification of the tool is achievable with good internal consistency and content validity. Further studies are needed to investigate if team-based self-monitoring may be used as part of a programme of assessment to target training programmes for observed performance gaps. © 2013 Stocker et al.; licensee BioMed Central Ltd

On a Jansen leg with multiple gait patterns for reconfigurable walking platforms

Legged robots are able to move across irregular terrains and those based on 1-degree-of-freedom planar linkages can be energy efficient, but are often constrained by a limited range of gaits which can limit their locomotion capabilities considerably. This article reports the design of a novel reconfigurable Theo Jansen linkage that produces a wide variety of gait cycles, opening new possibilities for innovative applications. The suggested mechanism switches from a pin-jointed Grübler kinematic chain to a 5-degree-of-freedom mechanism with slider joints during the reconfiguration process. It is shown that such reconfigurable linkage significantly extend the capabilities of the original design, while maintaining its mechanical simplicity during normal operation, to not only produce different useful gait patterns but also to realize behaviors beyond locomotion. Experiments with an implemented prototype are presented, and their results validate the proposed approach

From critters to cancers: bridging comparative and clinical research on oxygen sensing, HIF signaling, and adaptations towards hypoxia

The objective of this symposium at the First International Congress of Respiratory Biology (ICRB) was to enhance communication between comparative biologists and cancer researchers working on O2 sensing via the HIF pathway. Representatives from both camps came together on August 13-16, 2006, in Bonn, Germany, to discuss molecular adaptations that occur after cells have been challenged by a reduced (hypoxia) or completely absent (anoxia) supply of oxygen. This brief "critters-to-cancer” survey discusses current projects and new directions aimed at improving understanding of hypoxic signaling and developing therapeutic intervention

A Membrane-Bound Vertebrate Globin

The family of vertebrate globins includes hemoglobin, myoglobin, and other O2-binding proteins of yet unclear functions. Among these, globin X is restricted to fish and amphibians. Zebrafish (Danio rerio) globin X is expressed at low levels in neurons of the central nervous system and appears to be associated with the sensory system. The protein harbors a unique N-terminal extension with putative N-myristoylation and S-palmitoylation sites, suggesting membrane-association. Intracellular localization and transport of globin X was studied in 3T3 cells employing green fluorescence protein fusion constructs. Both myristoylation and palmitoylation sites are required for correct targeting and membrane localization of globin X. To the best of our knowledge, this is the first time that a vertebrate globin has been identified as component of the cell membrane. Globin X has a hexacoordinate binding scheme and displays cooperative O2 binding with a variable affinity (P50∼1.3–12.5 torr), depending on buffer conditions. A respiratory function of globin X is unlikely, but analogous to some prokaryotic membrane-globins it may either protect the lipids in cell membrane from oxidation or may act as a redox-sensing or signaling protein

In the wake of austerity: social impact bonds and the financialisation of the welfare state in Britain

This paper provides an analysis of the financialisation of the British welfare state. In a continuation of neo-liberal privatisation and labour market activation, the financialised welfare state pursues a policy of welfare retrenchment, while engaging in forms of social engineering aimed at producing self-responsibilised individuals and communities who are financially literate, ‘investment-ready’ and economically productive. New financial instruments such as social impact bonds are deployed to these ends, both to ‘solve social problems’ and enable cost saving. Through the use of such financial instruments, the implementation of regulatory infrastructures and tax incentives, the financialised welfare state becomes a vehicle for the transfer of wealth from the public to private investors, while subjecting the domain of social policy to the vicissitudes of global financial markets. This paper offers a critique of these developments, situating the case of Britain within the broader global context and with regard to the implications for understanding the current political economy of the welfare state

Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials

Introduction: This integrated analysis describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, at 15 and 30 mg once daily for up to 3 years of exposure in patients with active psoriatic arthritis (PsA) who had a prior inadequate response or intolerance to ≥ 1 non-biologic or biologic disease-modifying antirheumatic drug. Methods: Safety data were pooled and analyzed from two randomized, placebo-controlled phase 3 trials. Both trials evaluated upadacitinib 15 mg and 30 mg once daily, and one trial also evaluated adalimumab 40 mg every other week. Treatment-emergent adverse events (TEAEs) and laboratory data were summarized for four groups: pooled placebo, pooled upadacitinib 15 mg, pooled upadacitinib 30 mg, and adalimumab. TEAEs were reported as exposure-adjusted event rates (events per 100 patient-years [E/100 PY]) up to a data cut-off of June 29, 2020. Results: A total of 2257 patients received ≥ 1 dose of upadacitinib 15 mg (N = 907) or 30 mg (N = 921) for 2504.6 PY of exposure or adalimumab (N = 429) for 549.7 PY of exposure. Upper respiratory tract infection, nasopharyngitis, and increased creatine phosphokinase (CPK) were the most common TEAEs with upadacitinib. Rates of malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs), and deaths were similar across treatment groups. Rates of herpes zoster (HZ) and opportunistic infections (OI; excluding tuberculosis, HZ, and oral candidiasis) were higher with upadacitinib versus adalimumab. Serious infection, anemia, and CPK elevations were most frequent with upadacitinib 30 mg. Potentially clinically significant laboratory abnormalities were uncommon. Conclusions: Upadacitinib 15 mg and adalimumab had similar safety profiles with the exception of HZ and OIs, consistent with what was observed in rheumatoid arthritis. Rates of malignancies, MACEs, VTEs, and deaths were comparable among patients receiving upadacitinib and adalimumab. No new safety risks emerged with longer-term exposure to upadacitinib. Trial Registration Numbers: SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374