Method for Measurement of Viral Fusion Kinetics at the Single Particle Level

Membrane fusion is an essential step during entry of enveloped viruses into cells. Conventional fusion assays typically report on a large number of fusion events, making it difficult to quantitatively analyze the sequence of the molecular steps involved. We have developed an in vitro, two-color fluorescence assay to monitor kinetics of single virus particles fusing with a target bilayer on an essentially fluid support

Kinetics of proton transport into influenza virions by the viral M2 channel

M2 protein of influenza A viruses is a tetrameric transmembrane proton channel, which has essential functions both early and late in the virus infectious cycle. Previous studies of proton transport by M2 have been limited to measurements outside the context of the virus particle. We have developed an in vitro fluorescence-based assay to monitor internal acidification of individual virions triggered to undergo membrane fusion. We show that rimantadine, an inhibitor of M2 proton conductance, blocks the acidification-dependent dissipation of fluorescence from a pH-sensitive virus-content probe. Fusion-pore formation usually follows internal acidification but does not require it. The rate of internal virion acidification increases with external proton concentration and saturates with a pKm of ~4.7. The rate of proton transport through a single, fully protonated M2 channel is approximately 100 to 400 protons per second. The saturating proton-concentration dependence and the low rate of internal virion acidification derived from authentic virions support a transporter model for the mechanism of proton transfer

Imaginary Worlds: Using Visual Network Scales to Capture Perceptions of Social Networks

Social networks are not just patterns of interaction and sentiment in the real world; they are also cognitive (re)constructions of social relations, some real, some imagined. Focusing on networks as mental entities, our essay describes a new method that relies on stylized network images to gather quantitative data on how people “see” specific aspects of their social worlds. We discuss the logic of our approach, present several examples of “visual network scales,” discuss some preliminary findings, and identify some of the problems and prospects in this nascent line of work on the phenomenology of social networks

Bostonia: The Boston University Alumni Magazine. Volume 20

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

How was it for you? Experiences of participatory design in the UK health service

Improving co-design methods implies that we need to understand those methods, paying attention to not only the effect of method choices on design outcomes, but also how methods affect the people involved in co-design. In this article, we explore participants' experiences from a year-long participatory health service design project to develop ‘Better Outpatient Services for Older People’. The project followed a defined method called experience-based design (EBD), which represented the state of the art in participatory service design within the UK National Health Service. A sample of participants in the project took part in semi-structured interviews reflecting on their involvement in and their feelings about the project. Our findings suggest that the EBD method that we employed was successful in establishing positive working relationships among the different groups of stakeholders (staff, patients, carers, advocates and design researchers), although conflicts remained throughout the project. Participants' experiences highlighted issues of wider relevance in such participatory design: cost versus benefit, sense of project momentum, locus of control, and assumptions about how change takes place in a complex environment. We propose tactics for dealing with these issues that inform the future development of techniques in user-centred healthcare design

Effects of Varying Gravity Levels on fNIRS Headgear Performance and Signal Recovery

This paper reviews the effects of varying gravitational levels on functional Near-Infrared Spectroscopy (fNIRS) headgear. The fNIRS systems quantify neural activations in the cortex by measuring hemoglobin concentration changes via optical intensity. Such activation measurement allows for the detection of cognitive state, which can be important for emotional stability, human performance and vigilance optimization, and the detection of hazardous operator state. The technique depends on coupling between the fNIRS probe and users skin. Such coupling may be highly susceptible to motion if probe-containing headgear designs are not adequately tested. The lack of reliable and self-applicable headgear robust to the influence of motion artifact currently inhibits its operational use in aerospace environments. Both NASAs Aviation Safety and Human Research Programs are interested in this technology as a method of monitoring cognitive state of pilots and crew

Redistribution of Nickel Ions Embedded within Indium Phosphide Via Low Energy Dual Ion Implantations

Transition-metal doped Indium Phosphide (InP) has been studied over several decades for utilization in optoelectronics applications. Recently, interesting magnetic properties have been reported for metal clusters formed at different depths surrounded by a high quality InP lattice. In this work, we have reported accumulation of Ni atoms at various depths in InP via implantation of Ni- followed by H– and subsequently thermal annealing. Prior to the ion implantations, the ion implant depth profile was simulated using an ion-solid interaction code SDTrimSP, incorporating dynamic changes in the target matrix during ion implantation. Initially, 50 keV Ni- ions are implanted with a fluence of 2 × 1015 atoms cm-2, with a simulated peak deposition profile approximately 42 nm from the surface. 50 keV H- ions are then implanted with a fluence of 1.5 × 1016 atoms cm-2. The simulation result indicates that the H- creates damages with a peak defect center ~400 nm below the sample surface. The sample has been annealed at 50°C in an Ar rich environment for approximately 1hr. During the annealing, H vacates the lattice, and the formed nano-cavities act as trapping sites and a gettering effect for Ni diffusion into the substrate. The distribution of Ni atoms in InP samples are estimated by utilizing Rutherford Backscattering Spectrometry and X-ray Photoelectron Spectroscopy based depth profiling while sputtering the sample with Ar-ion beams. In the sample annealed after H implantation, the Ni was found to migrate to deeper depths of 125 nm than the initial end of range of 70 nm

Key Technical Challenges for the Electric Power Industry and Climate Change

This paper, prepared by the Climate Change Technology Subcommittee, a subcommittee of the Power and Energy Society Energy Development and Power Generation Committee, identifies key technical issues facing the electric power industry, related to global climate change. The technical challenges arise from: 1) impacts on system operating strategies, configuration, and expansion plans of emission-reducing technologies; 2) power infrastructure response to extreme weather events; 3) effects of government policies including an expanded use of renewable and alternative energy technologies; and 4) impacts of market rules on power system operation. Possible lessons from other industries\u27 responses to climate change are explored

c-di-GMP modulates type IV MSHA pilus retraction and surface attachment in Vibrio cholerae.

Biofilm formation by Vibrio cholerae facilitates environmental persistence, and hyperinfectivity within the host. Biofilm formation is regulated by 3',5'-cyclic diguanylate (c-di-GMP) and requires production of the type IV mannose-sensitive hemagglutinin (MSHA) pilus. Here, we show that the MSHA pilus is a dynamic extendable and retractable system, and its activity is directly controlled by c-di-GMP. The interaction between c-di-GMP and the ATPase MshE promotes pilus extension, whereas low levels of c-di-GMP correlate with enhanced retraction. Loss of retraction facilitated by the ATPase PilT increases near-surface roaming motility, and impairs initial surface attachment. However, prolonged retraction upon surface attachment results in reduced MSHA-mediated surface anchoring and increased levels of detachment. Our results indicate that c-di-GMP directly controls MshE activity, thus regulating MSHA pilus extension and retraction dynamics, and modulating V. cholerae surface attachment and colonization

Evolution of Hominin Polyunsaturated Fatty Acid Metabolism: From Africa to the New World

The metabolic conversion of dietary omega-3 and omega-6 18 carbon (18C) to long chain (>20 carbon) polyunsaturated fatty acids (LC-PUFAs) is vital for human life. The rate-limiting steps of this process are catalyzed by fatty acid desaturase (FADS) 1 and 2. Therefore, understanding the evolutionary history of the FADS genes is essential to our understanding of hominin evolution. The FADS genes have two haplogroups, ancestral and derived, with the derived haplogroup being associated with more efficient LC-PUFA biosynthesis than the ancestral haplogroup. In addition, there is a complex global distribution of these haplogroups that is suggestive of Neanderthal introgression. We confirm that Native American ancestry is nearly fixed for the ancestral haplogroup, and replicate a positive selection signal in Native Americans. This positive selection potentially continued after the founding of the Americas, although simulations suggest that the timing is dependent on the allele frequency of the ancestral Beringian population. We also find that the Neanderthal FADS haplotype is more closely related to the derived haplogroup and the Denisovan clusters closer to the ancestral haplogroup. Furthermore, the derived haplogroup has a time to the most recent common ancestor of 688,474years before present. These results support an ancient polymorphism, as opposed to Neanderthal introgression, forming in the FADS region during the Pleistocene with possibly differential selection pressures on both haplogroups. The near fixation of the ancestral haplogroup in Native American ancestry calls for future studies to explore the potential health risk of associated low LC-PUFA levels in these populations.Center for Health Related Informatics and Biomaging at the University of Maryland School of Medicine; National Institutes of Health/National Heart, Lung, and Blood Institute [U01 HL72518, HL087698, HL112064]; National Institutes of Health [R01-AT008621]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]