Synthetic antibodies against BRIL as universal fiducial marks for single−particle cryoEM structure determination of membrane proteins

We propose the concept of universal fiducials based on a set of pre-made semi-synthetic antibodies (sABs) generated by customized phage display selections against the fusion protein BRIL, an engineered variant of apocytochrome b562a. These sABs can bind to BRIL fused either into the loops or termini of different GPCRs, ion channels, receptors and transporters without disrupting their structure. A crystal structure of BRIL in complex with an affinity-matured sAB (BAG2) that bound to all systems tested delineates the footprint of interaction. Negative stain and cryoEM data of several examples of BRIL-membrane protein chimera highlight the effectiveness of the sABs as universal fiducial marks. Taken together with a cryoEM structure of sAB bound human nicotinic acetylcholine receptor, this work demonstrates that these anti-BRIL sABs can greatly enhance the particle properties leading to improved cryoEM outcomes, especially for challenging membrane proteins

Synthetic antibodies against BRIL as universal fiducial marks for single-particle cryoEM structure determination of membrane proteins

We propose the concept of universal fiducials based on a set of pre-made semi-synthetic antibodies (sABs) generated by customized phage display selections against the fusion protein BRIL, an engineered variant of apocytochrome b562a. These sABs can bind to BRIL fused either into the loops or termini of different GPCRs, ion channels, receptors and transporters without disrupting their structure. A crystal structure of BRIL in complex with an affinity-matured sAB (BAG2) that bound to all systems tested delineates the footprint of interaction. Negative stain and cryoEM data of several examples of BRIL-membrane protein chimera highlight the effectiveness of the sABs as universal fiducial marks. Taken together with a cryoEM structure of sAB bound human nicotinic acetylcholine receptor, this work demonstrates that these anti-BRIL sABs can greatly enhance the particle properties leading to improved cryoEM outcomes, especially for challenging membrane proteins

Researching the ethical dimensions of mobile, ubiquitous,and immersive technology enhanced learning (MUITEL) in informal settings: a thematic review and dialogue

In this paper we examine the ethical dimensions of researching the mobile, ubiquitous and immersive dimensions of technology enhanced learning (MUITEL), with a particular focus on learning in informal settings. We begin with an analysis of the interactions between mobile, ubiquitous and immersive technologies and the wider context of the digital economy. In this analysis we identify social, economic and educational developments that blur boundaries: between the individual and the consumer, between the formal and the informal, between education and other forms of learning. This leads to a complex array of possibilities for learning designs, and an equally complex array of ethical dimensions and challenges. We then examine the recent literature on the ethical dimensions of TEL research, and identify key trends, ethical dilemmas, and issues for researchers investigating MUITEL in informal educational settings. We then present a summary of research dialogue between the authors (as TEL researchers) to illuminate these MUITEL research challenges, indicating new trends in ethical procedure that may offer inspiration for other researchers. We conclude with an outline, derived from the foregoing analysis, of ways in which ethical guidelines and processes can be developed by researchers - through interacting with participants and other professionals. We conclude that ethical issues need to remain as open questions and be revisited as part of research practices. Because technologies and relationships develop, reassessments will always be required in the light of new understandings. We hope this analysis will motivate and support continued reflection and discussion about how to conduct ethically committed MUITEL research

Male song sparrows have elevated testosterone in response to neighbors versus strangers

Upon hearing a conspecific signal, animals must assess their relationship with the signaller and respond appropriately. Territorial animals usually respond more aggressively to strangers than neighbors in a phenomenon known as the “dear enemy effect”. This phenomenon likely evolved because strangers represent a threat to an animal\u27s territory tenure and parentage, whereas neighbors only represent a threat to an animal\u27s parentage because they already possess a territory (providing territory boundaries are established and stable). Although the dear enemy effect has been widely documented using behavioral response variables, little research has been conducted on the physiological responses of animals to neighbors versus strangers. We sought to investigate whether the dear enemy effect is observed physiologically by exposing territorial male song sparrows (Melospiza melodia) to playback simulating a neighbor or a stranger, and then collecting blood samples to measure plasma testosterone levels. We predicted that song sparrows would exhibit increased testosterone levels after exposure to stranger playback compared to neighbor playback, due to the role testosterone plays in regulating aggression. Contrary to our prediction, we found that song sparrows had higher testosterone levels after exposure to neighbor playback compared to stranger playback. We discuss several explanations for our result, notably that corticosterone may regulate the dear enemy effect in male song sparrows and this may inhibit plasma testosterone. Future studies will benefit from examining corticosterone in addition to testosterone, to better understand the hormonal underpinnings of the dear enemy effect. © 2017 Elsevier Inc

Developing Quality Indicators for Family Support Services in Community Team-Based Mental Health Care

Turkey-Mersin Bread Sellerhttps://scholarworks.harding.edu/hst-lewis-slides/6326/thumbnail.jp

Spleen Size and Function in Sherpa Living High, Sherpa Living Low and Nepalese Lowlanders

High-altitude (HA) natives have evolved some beneficial responses leading to superior work capacity at HA compared to native lowlanders. Our aim was to study two responses potentially protective against hypoxia: the spleen contraction elevating hemoglobin concentration (Hb) and the cardiovascular diving response in Sherpa highlanders, compared to lowlanders. Male participants were recruited from three groups: (1) 21 Sherpa living at HA (SH); (2) seven Sherpa living at low altitude (SL); and (3) ten native Nepalese lowlanders (NL). They performed three apneas spaced by a two-min rest at low altitude (1370 m). Their peripheral oxygen saturation (SpO(2)), heart rate (HR), and spleen volume were measured across the apnea protocol. Spleen volume at rest was 198 +/- 56 mL in SH and 159 +/- 35 mL in SL (p= 0.047). The spleen was larger in Sherpa groups compared to the 129 +/- 22 mL in NL (p< 0.001 compared to SH;p= 0.046 compared to SL). Spleen contraction occurred in all groups during apnea, but it was greater in Sherpa groups compared to NL (p< 0.001). HR was lower in Sherpa groups compared to NL both during rest (SL:p< 0.001; SH:p= 0.003) and during maximal apneas (SL:p< 0.001; SH:p= 0.06). The apnea-induced HR reduction was 8 +/- 8% in SH, 10 +/- 4% in SL (NS), and 18 +/- 6% in NL (SH:p= 0.005; SL:p= 0.021 compared to NL). Resting SpO(2)was similar in all groups. The progressively decreasing baseline spleen size across SH, SL, and NL suggests a role of the spleen at HA and further that both genetic predisposition and environmental exposure determine human spleen size. The similar HR responses of SH and SL suggest that a genetic component is involved in determining the cardiovascular diving response

Quality of radiotherapy reporting in randomized controlled trials of Hodgkin\u27s lymphoma and non-Hodgkin\u27s lymphoma: in regard to Bekelman and Yahalom (Int J Radiat Oncol Biol Phys 2009;73:492-498)

Comment on Quality of radiotherapy reporting in randomized controlled trials of Hodgkin\u27s lymphoma and non-Hodgkin\u27s lymphoma: a systematic review. [Int J Radiat Oncol Biol Phys. 2009