Structural and functional studies of the terminal protein complex of the human complement system

The membrane attack complex (MAC: C5blC61C71C81C9n) is the terminal complex of the mammalian complement cascade. Its principal function is to form a self-assembling, potentially cytolytic pore spanning the membrane of a foreign cell. However, inappropriate complement activation and subsequent aberrant MAC action is responsible for tissue damage in several human pathologies.1 The C-terminal domains or modules that are exclusive to the C6 and C7 components of the MAC, form a putative molecular arm. These modules consist of two complement control protein modules (CCPs) followed by a pair of Factor I-like Modules (FIMs). The C-terminal molecular arms of C6 and C7 are important for linking the complement activation cascade with MAC assembly and thereby ensuring MAC assembly occurs only when needed. They interact with the C345C domain of C5 and C5b. Currently there are no high-resolution structural data for any of the MAC components but efforts are underway to solve the structures of the individual domains. For instance, the structure of the central MAC/perforin domain of C8 has been determined, so has the structure of C5 and the FIM domains of C7. However , the lack of structural information for the MAC is being balanced by an increased understanding of mechanism, and eventually towards the rational design of therapies designed to supress MAC formation.This report describes the preparation from bacterial and yeast cells of ¹³C,¹⁵N-labelled samples of the C7 CCP-pair and of a triple module consisting of the second CCP followed by the FIM-pair, as well as other constructs from the C6 and C7 C-terminal arms. The NMR samples were used to solve 3D solutions of structures, thus allowing for reconstruction of the four-module C-terminus of C7. Efforts were aimed at obtaining additional structural information for C7. This included SAXS analysis as well as the development of a novel approach using chemical cross-linking followed by tryptic digestion and mass spectrometry-based identification of cross-linked peptides

Improving Student Outcomes: A Framework for Effective Oral Feedback

“Feedback is one of the most powerful influences on learning and achievement, but this impact can be either positive or negative” (Hattie & Timperley, 2007, p. 81). However, finding time and developing an approach for structured and quality feedback often proves problematic. Providing feedback may seem valueless if students do not interact with it, thus we developed the 5R+ feedback method as a solution using VoiceThread as the platform

Reduction in the efficiency of light use due to disease

Foram estudados os efeitos de uma micose causada por Ascochyta fabae na intercepção de luz solar pelo copado e no crescimento de Vicia faba, durante o seu cultivo no campo (Universidade de Nottingham, Inglaterra). Infecções precoces reduziram a “duração da área foliar” e a “eficiência de utilização de luz”, originando um decréscimo na produção de matéria seca da culturainfo:eu-repo/semantics/publishedVersio

Primary palliative care in southern Brazil: the legacy of Cicely Saunders

No abstract available

Archiving Interactive Narratives at the British Library

This paper describes the creation of the Interactive Narratives collection in the UK Web Archive, as part of the UK Legal Deposit Libraries Emerging Formats Project. The aim of the project is to identify, collect and preserve complex digital publications that are in scope for collection under UK Non-Print Legal Deposit Regulations. This article traces the process of building the Interactive Narratives collection, analysing the different tools and methods used and placing the collection within the wider context of Emerging Formats work and engagement activities at the British Library

Do program practices matter for mentors?: How implementation of empirically supported program practices is associated with youth mentoring relationship quality

This study investigates how the implementation of program-level practices by formal youth mentoring programs is associated with the quality of youth mentoring relationships as contexts for youth development and also examines whether this connection is mediated by the mentor-staff working alliance. Using data from mentors (n = 542) participating in multiple programs (n = 55), multilevel path models examined hypothesized direct and mediated effects. Parallel analyses were conducted with assessments of program practices from staff (n = 219). Greater exposure to program practices was associated with higher ratings of mentoring relationship satisfaction, commitment, and security and lower mentor-youth relationship negativity. The mentor-staff working alliance either partially or fully mediated these associations. Staff-reported practices predicted mentoring relationship satisfaction and commitment without mediation by the working alliance. This study suggests program practices contribute to stronger youth mentoring relationships. The findings also highlight the mentor-staff working alliance in supporting the development of positive mentoring relationships

Electrophysiological properties of human beta-cell lines EndoC-βH1 and -βH2 conform with human beta-cells

© The Author(s) 2018Limited access to human islets has prompted the development of human beta cell models. The human beta cell lines EndoC-βH1 and EndoC-βH2 are increasingly used by the research community. However, little is known of their electrophysiological and secretory properties. Here, we monitored parameters that constitute the glucose-triggering pathway of insulin release. Both cell lines respond to glucose (6 and 20 mM) with 2- to 3-fold stimulation of insulin secretion which correlated with an elevation of [Ca2+]i, membrane depolarisation and increased action potential firing. Similar to human primary beta cells, KATP channel activity is low at 1 mM glucose and is further reduced upon increasing glucose concentration; an effect that was mimicked by the KATP channel blocker tolbutamide. The upstroke of the action potentials reflects the activation of Ca2+ channels with some small contribution of TTX-sensitive Na+ channels. The repolarisation involves activation of voltage-gated Kv2.2 channels and large-conductance Ca2+-activated K+ channels. Exocytosis presented a similar kinetics to human primary beta cells. The ultrastructure of these cells shows insulin vesicles composed of an electron-dense core surrounded by a thin clear halo. We conclude that the EndoC-βH1 and -βH2 cells share many features of primary human β-cells and thus represent a useful experimental model.Peer reviewedFinal Published versio

Concurrent panel session 2: Challenges facing our youth and aged populations

Moderator: Dr. Ann McDonough, UNLV Gerontology Program Scribe: Lisa Gioia-Acres, UNLV Department of History Conference white paper & Full summary of panel session, 4 page

RBC barcoding allows for the study of erythrocyte population dynamics and P. falciparum merozoite invasion.

Plasmodium falciparum invasion of host erythrocytes is essential for the propagation of the blood stage of malaria infection. Additionally, the brief extracellular merozoite stage of P. falciparum represents one of the rare windows during which the parasite is directly exposed to the host immune response. Therefore, efficient invasion of the host erythrocyte is necessary not only for productive host erythrocyte infection, but also for evasion of the immune response. Host traits, such as hemoglobinopathies and differential expression of erythrocyte invasion ligands, can protect individuals from malaria by impeding parasite erythrocyte invasion. Here we combine RBC barcoding with flow cytometry to study P. falciparum invasion. This novel high-throughput method allows for the (i) direct comparison of P. falciparum invasion into different erythrocyte populations and (ii) assessment of the impact of changing erythrocyte population dynamics on P. falciparum invasion