Expression of Escherichia coli F-18 Type 1 Fimbriae in the Streptomycin-Treated Mouse Large Intestine

Escherichia coli F-18, isolated from the feces of a healthy human, makes type 1 fimbriae and is an excellent colonizer of the streptomycin-treated mouse large intestine. Recently, it was shown that the inability to produce type 1 fimbriae had no effect on the ability of E. coli F-18 to colonize the streptomycin-treated mouse large intestine, suggesting the possibility that E. coli F-18 does not express type 1 fimbriae in vivo. However, we show here that E. coli F-18 does express type 1 fimbriae in mouse cecal mucus in vivo and, in fact, appears to express substantially more type 1 fimbriae in cecal mucus in vivo than in L broth in vitro

Site‐specific encoding of photoactivity in antibodies enables light‐mediated antibody‐antigen binding on live cells

Antibodies have found applications in several fields, including, medicine, diagnostics, and nanotechnology, yet methods to modulate antibody‐antigen binding using an external agent remain limited. Here, we have developed photoactive antibody fragments by genetic site‐specific replacement of single tyrosine residues with photocaged tyrosine, in an antibody fragment, 7D12. A simple and robust assay is adopted to evaluate the light‐mediated binding of 7D12 mutants to its target, epidermal growth factor receptor (EGFR), on the surface of cancer cells. Presence of photocaged tyrosine reduces 7D12‐EGFR binding affinity by over 20‐fold in two out of three 7D12 mutants studied, and binding is restored upon exposure to 365 nm light. Molecular dynamics simulations explain the difference in effect of photocaging on 7D12‐EGFR interaction among the mutants. Finally, we demonstrate the application of photoactive antibodies in delivering fluorophores to EGFR‐positive live cancer cells in a light‐dependent manner

Performance and Life Tests of a Regenerative Blower for EVA Suit Ventilation

Ventilation fans for future space suits must meet demanding performance specifications, satisfy stringent safety requirements for operation in an oxygen atmosphere, and be able to increase output to operate in buddy mode. A regenerative blower is an attractive choice due to its ability to meet these requirements at low operating speed. This paper describes progress in the development and testing of a regenerative blower designed to meet requirements for ventilation subsystems in future space suits. The blower includes a custom-designed motor that has significantly improved its efficiency. We have measured the blower s head/flow performance and power consumption under conditions that simulate both the normal and buddy mode operating points. We have operated the blower for TBD hours and demonstrated safe operation in an oxygen test loop at prototypical pressures. We also demonstrated operation with simulated lunar dust

Influenza A Virus Host Shutoff Disables Antiviral Stress-Induced Translation Arrest

Influenza A virus (IAV) polymerase complexes function in the nucleus of infected cells, generating mRNAs that bear 5′ caps and poly(A) tails, and which are exported to the cytoplasm and translated by host machinery. Host antiviral defences include mechanisms that detect the stress of virus infection and arrest cap-dependent mRNA translation, which normally results in the formation of cytoplasmic aggregates of translationally stalled mRNA-protein complexes known as stress granules (SGs). It remains unclear how IAV ensures preferential translation of viral gene products while evading stress-induced translation arrest. Here, we demonstrate that at early stages of infection both viral and host mRNAs are sensitive to drug-induced translation arrest and SG formation. By contrast, at later stages of infection, IAV becomes partially resistant to stress-induced translation arrest, thereby maintaining ongoing translation of viral gene products. To this end, the virus deploys multiple proteins that block stress-induced SG formation: 1) non-structural protein 1 (NS1) inactivates the antiviral double-stranded RNA (dsRNA)-activated kinase PKR, thereby preventing eIF2α phosphorylation and SG formation; 2) nucleoprotein (NP) inhibits SG formation without affecting eIF2α phosphorylation; 3) host-shutoff protein polymerase-acidic protein-X (PA-X) strongly inhibits SG formation concomitant with dramatic depletion of cytoplasmic poly(A) RNA and nuclear accumulation of poly(A)-binding protein. Recombinant viruses with disrupted PA-X host shutoff function fail to effectively inhibit stress-induced SG formation. The existence of three distinct mechanisms of IAV-mediated SG blockade reveals the magnitude of the threat of stress-induced translation arrest during viral replication

Staying true with the help of others: doxastic self-control through interpersonal commitment

I explore the possibility and rationality of interpersonal mechanisms of doxastic self-control, that is, ways in which individuals can make use of other people in order to get themselves to stick to their beliefs. I look, in particular, at two ways in which people can make interpersonal epistemic commitments, and thereby willingly undertake accountability to others, in order to get themselves to maintain their beliefs in the face of anticipated “epistemic temptations”. The first way is through the avowal of belief, and the second is through the establishment of collective belief. I argue that both of these forms of interpersonal epistemic commitment can function as effective tools for doxastic self-control, and, moreover, that the control they facilitate should not be dismissed as irrational from an epistemic perspective

Self-regulation in endurance sports: theory, research, and practice

There is considerable research interest in psychological aspects of endurance performance. Until recently, research typically lacked a theoretical underpinning, and contemporary research is particularly informed by the psychobiological model of endurance performance. In this critical review, we propose that psychological theories relating to self-regulation, particularly self-efficacy theory and the process model of emotion regulation, could shed more light on how endurance performance is determined and lead to additional understanding of how psychological interventions can be used. We argue that people encounter fewer stressors in most experimental studies than are encountered before and during real-life events. In addition, we argue that most research conducted to date has focused on the forethought and performance phases of self-regulation, rather than the self-reflection phase, and research has not considered the cyclical nature of self-regulation. We also argue that if research participants are not endurance athletes, then their motivation may not be self-determined, and self-regulatory learning may not take place. Recommendations are given for future research, and evidence-based guidance is offered on enhancing performance and improving the quality of experience for endurance athletes

Technology-dependent rehabilitation involving action observation and movement imagery for adults with stroke: can it work? Feasibility of self-led therapy for upper limb rehabilitation after stroke

Background. Motor (re)learning via technology-dependent therapy has the potential to complement traditional therapies available to older adults living with stroke after hospital discharge and increase therapy dose. To date, little is known about the feasibility of technology-dependent therapy in a home setting for this population. Objective. To develop a technology-dependent therapy that provides mental and physical training for older adults with stroke and assess feasibility. Specifically we ask, "Can it work"? Design. Single group repeated measures. Methods. 13 participants, aged 18 years and over, were recruited over a six-month period. All participants had mild upper limb impairment following a stoke and were no longer receiving intensive rehabilitation. All participants received 18 days of technology-dependent therapy in their own home. Information was gathered on recruitment and retention, usability, and suitability of outcome measures. Results. 11 participants completed the study. The recruitment rate (number recruited/number canvassed; 10.7%) suggests 1907 participants would need to be canvassed to recruit the necessary sample size (n=204) for a definitive trial designed to provide 90% power at 5% level of significance to detect a clinically meaningful difference of 5.7 points on the Action Research Arm Test. The usability of the application was rated as exceptional on the System Usability Scale. Effectiveness cannot be determined from this study; however, there was a trend for improvement in measures of upper limb function and emotional well-being. Limitations. The study was limited by a relatively small sample size and lack of control group. Conclusions. This study demonstrated proof of concept of a technology-dependent therapy for upper limb rehabilitation following stroke. The data suggest a definitive trial is feasible, additional strategies to improve recruitment should be considered. Outcome measures aligned with the residual motor function of participants are required

The Impact of a Six‐Year Climate Anomaly on the “Spanish Flu” Pandemic and WWI

The H1N1 “Spanish influenza” pandemic of 1918–1919 caused the highest known number of deaths recorded for a single pandemic in human history. Several theories have been offered to explain the virulence and spread of the disease, but the environmental context remains underexamined. In this study, we present a new environmental record from a European, Alpine ice core, showing a significant climate anomaly that affected the continent from 1914 to 1919. Incessant torrential rain and declining temperatures increased casualties in the battlefields of World War I (WWI), setting the stage for the spread of the pandemic at the end of the conflict. Multiple independent records of temperature, precipitation, and mortality corroborate these findings

Pre-Treatment With Glucagon-Like Peptide-1 Protects Against Ischemic Left Ventricular Dysfunction and Stunning Without a Detected Difference in Myocardial Substrate Utilization

AbstractObjectivesThis study sought to determine whether pre-treatment with intravenous glucagon-like peptide-1 (GLP-1)(7-36) amide could alter myocardial glucose use and protect the heart against ischemic left ventricular (LV) dysfunction during percutaneous coronary intervention.BackgroundGLP-1 has been shown to have favorable cardioprotective effects, but its mechanisms of action remain unclear.MethodsTwenty patients with preserved LV function and single-vessel left anterior descending coronary artery disease undergoing elective percutaneous coronary intervention were studied. A conductance catheter was placed into the LV, and pressure-volume loops were recorded at baseline, during 1-min low-pressure balloon occlusion (BO), and at 30-min recovery. Patients were randomized to receive an infusion of either GLP-1(7-36) amide at 1.2 pmol/kg/min or saline immediately after baseline measurements. Simultaneous coronary artery and coronary sinus blood sampling was performed at baseline and after BO to assess transmyocardial glucose concentration gradients.ResultsBO caused both ischemic LV dysfunction and stunning in the control group but not in the GLP-1 group. Compared with control subjects, the GLP-1 group had a smaller reduction in LV performance during BO (delta dP/dTmax, –4.3 vs. –19.0%, p = 0.02; delta stroke volume, –7.8 vs. –26.4%, p = 0.05), and improved LV performance at 30-min recovery. There was no difference in transmyocardial glucose concentration gradients between the 2 groups.ConclusionsPre-treatment with GLP-1(7-36) amide protects the heart against ischemic LV dysfunction and improves the recovery of function during reperfusion. This occurs without a detected change in myocardial glucose extraction and may indicate a mechanism of action independent of an effect on cardiac substrate use. (Effect of Glucgon-Like-Peptide-1 [GLP-1] on Left Ventricular Function During Percutaneous Coronary Intervention [PCI]; ISRCTN77442023