Overcoming barriers to membrane protein structure determination

After decades of slow progress, the pace of research on membrane protein structures is beginning to quicken thanks to various improvements in technology, including protein engineering and microfocus X-ray diffraction. Here we review these developments and, where possible, highlight generic new approaches to solving membrane protein structures based on recent technological advances. Rational approaches to overcoming the bottlenecks in the field are urgently required as membrane proteins, which typically comprise ~30% of the proteomes of organisms, are dramatically under-represented in the structural database of the Protein Data Bank.

Overcoming bottlenecks in the membrane protein structural biology pipeline

Membrane proteins account for a third of the eukaryotic proteome, but are greatly under-represented in the Protein Data Bank. Unfortunately, recent technological advances in X-ray crystallography and EM cannot account for the poor solubility and stability of membrane protein samples. A limitation of conventional detergent-based methods is that detergent molecules destabilize membrane proteins, leading to their aggregation. The use of orthologues, mutants and fusion tags has helped improve protein stability, but at the expense of not working with the sequence of interest. Novel detergents such as glucose neopentyl glycol (GNG), maltose neopentyl glycol (MNG) and calixarene-based detergents can improve protein stability without compromising their solubilizing properties. Styrene maleic acid lipid particles (SMALPs) focus on retaining the native lipid bilayer of a membrane protein during purification and biophysical analysis. Overcoming bottlenecks in the membrane protein structural biology pipeline, primarily by maintaining protein stability, will facilitate the elucidation of many more membrane protein structures in the near future.

Representation of people of South Asian origin in cardiovascular outcome trials of glucose-lowering therapies in Type 2 diabetes

Aims : Our aim was to investigate the proportional representation of people of South Asian origin in cardiovascular outcome trials of glucose-lowering drugs or strategies in Type 2 diabetes, noting that these are among the most significant pieces of evidence used to formulate the guidelines on which clinical practice is largely based. Methods : We searched for cardiovascular outcome trials in Type 2 diabetes published before January 2015, and extracted data on the ethnicity of participants. These were compared against expected values for proportional representation of South Asian individuals, based on population data from the USA, from the UK, and globally. Results : Twelve studies met our inclusion criteria and, of these, eight presented a sufficiently detailed breakdown of participant ethnicity to permit numerical analysis. In general, people of South Asian origin were found to be under-represented in trials compared with UK and global expectations and over-represented compared with US expectations. Among the eight trials for which South Asian representation could be reliably estimated, seven under-represented this group relative to the 11.2% of the UK diabetes population estimated to be South Asian, with the representation in these trials ranging from 0.0% to 10.0%. Conclusions : Clinicians should exercise caution when generalizing the results of trials to their own practice, with regard to the ethnicity of individuals. Efforts should be made to improve reporting of ethnicity and improve diversity in trial recruitment, although we acknowledge that there are challenges that must be overcome to make this a reality.

A content analysis of selected recreational therapy journals from 1990 to 1998: The extent to which children and youth are included

This paper presents an analysis of articles involving children and youth in the last 9 years (1990–1998) of professional literature in recreational therapy. A total of 539 articles were analyzed to examine the authors, subjects, methods, and outcomes of therapeutic recreation studies published in three selected journals: Therapeutic Recreation Journal, Leisure Studies , and Leisure Sciences. A central finding was that the literature involving children and youth was very under-represented in the journals. Only 6.5% of the articles targeted children and youth; of this group, approximately two thirds were research-based; the remaining articles were conceptual papers. The findings are discussed in terms of the need for future scholarships in recreational therapy to target children and youth, including those with disabilities. ^

Toward equity through participation in Modeling Instruction in introductory university physics

We report the results of a five year evaluation of the reform of introductory calculus-based physics by implementation of Modeling Instruction (MI) at Florida International University (FIU), a Hispanic-serving institution. MI is described in the context of FIU’s overall effort to enhance student participation in physics and science broadly. Our analysis of MI from a “participationist” perspective on learning identifies aspects of MI including conceptually based instruction, culturally sensitive instruction, and cooperative group learning, which are consistent with research on supporting equitable learning and participation by students historically under-represented in physics (i.e., Black, Hispanic, women). This study uses markers of conceptual understanding as measured by the Force Concept Inventory (FCI) and odds of success as measured by the ratio of students completing introductory physics and earning a passing grade (i.e., C− or better) by students historically under-represented in physics to reflect equity and participation in introductory physics. FCI pre and post scores for students in MI are compared with lecture-format taught students. Modeling Instruction students outperform students taught in lecture-format classes on post instruction FCI (61.9% vs 47.9%, p

Validation study of the Colorado Learning Attitudes about Science Survey at a Hispanic-serving institution

The Colorado Learning Attitudes about Science Survey (CLASS) has been widely acknowledged as a useful measure of student cognitive attitudes about science and learning. The initial University of Colorado validation study included only 20% non-Caucasian student populations. In this Brief Report we extend their validation to include a predominately under-represented minority population. We validated the CLASS instrument at Florida International University, a Hispanic-serving institution, by interviewing students in introductory physics classes using a semistructured protocol, examining students’ responses on the CLASS item statements, and comparing them to the items’ intended meaning. We find that in our predominately Hispanic population, 94% of the students’ interview responses indicate that the students interpret the CLASS items correctly, and thus the CLASS is a valid instrument. We also identify one potentially problematic item in the instrument which one third of the students interviewed consistently misinterpreted.

The Timing of Motherhood While Earning a PhD in Engineering

In spite of tremendous efforts, women are still under-represented in the field of science. Post-graduate education and early tenure track employment are part of the academic career establish-ment in research and development during periods that usually overlap with family formation. Though women tend to leave science mainly after obtaining their PhD, and the timing of mother-hood plays a vital role in a successful research career, qualitative data on this life period are scarce. Our paper focuses on how the normative and institutional contexts shape female PhD engineering students’ family plans. The research was based on intersections of life course and risk and uncertainty theories. Using qualitative interviews we explored how contradicting social norms of childbearing cause tensions in postgraduate students’ lives, and how the different uncer-tainties and risks permeate young researchers’ decisions on early life events. We concluded that, despite the general pattern of delaying motherhood among higher educated women, these students struggle against this postponement, and they hardly have any good options to avoid risk stem-ming from uncertainties and from some characteris-tics of studying and working in engineering. Find-ings of this research may call the attention of stake-holders to possible intervention points.

Diagnóstico del rendimiento académico de estudiantes de una escuela de educación superior en México

El objetivo del artículo es realizar un diagnóstico sobre la percepción de los factores que intervienen en el rendimiento académico de los estudiantes de cinco carreras universitarias en una escuela de educación superior en México, para así reconocer las áreas de oportunidad que permitan sugerir políticas y estrategias para elevar su rendimiento. Se utilizó una muestra de 1651 estudiantes, se obtuvieron los datos a partir de un cuestionario con treinta preguntas que estudian la percepción del rendimiento académico en escala tipo Likert. Se realizó un análisis factorial exploratorio que permitiera reducir los datos, facilitar la interpretación y validar el instrumento. Se identificaron tres factores: a) el rol de los profesores, b) la evaluación y c) la motivación de los estudiantes. Se llevó a cabo un análisis comparativo por carrera. Se encontró que los estudiantes perciben que la mayoría de los maestros no se preocupan por la condición de los jóvenes en situación de reprobación. Además, casi no motivan y carecen de expresiones de sentimientos de orgullo por los logros académicos de los estudiantes. La mitad de los participantes piensa que los docentes no cubren el temario en su totalidad. Se detectó que los estudiantes poseen una alta motivación siendo esto positivo porque son alumnos dedicados y responsables. Se concluye realizando una serie de sugerencias y explicando las implicaciones que tiene este trabajo para las instituciones de educación superior.

Underway spectrophotometry along the Atlantic Meridional Transect reveals high performance in satellite chlorophyll retrievals

To evaluate the performance of ocean-colour retrievals of total chlorophyll-a concentration requires direct comparison with concomitant and co-located in situ data. For global comparisons, these in situ match-ups should be ideally representative of the distribution of total chlorophyll-a concentration in the global ocean. The oligotrophic gyres constitute the majority of oceanic water, yet are under-sampled due to their inaccessibility and under-represented in global in situ databases. The Atlantic Meridional Transect (AMT) is one of only a few programmes that consistently sample oligotrophic waters. In this paper, we used a spectrophotometer on two AMT cruises (AMT19 and AMT22) to continuously measure absorption by particles in the water of the ship's flow-through system. From these optical data continuous total chlorophyll-a concentrations were estimated with high precision and accuracy along each cruise and used to evaluate the performance of ocean-colour algorithms. We conducted the evaluation using level 3 binned ocean-colour products, and used the high spatial and temporal resolution of the underway system to maximise the number of match-ups on each cruise. Statistical comparisons show a significant improvement in the performance of satellite chlorophyll algorithms over previous studies, with root mean square errors on average less than half (~ 0.16 in log10 space) that reported previously using global datasets (~ 0.34 in log10 space). This improved performance is likely due to the use of continuous absorption-based chlorophyll estimates, that are highly accurate, sample spatial scales more comparable with satellite pixels, and minimise human errors. Previous comparisons might have reported higher errors due to regional biases in datasets and methodological inconsistencies between investigators. Furthermore, our comparison showed an underestimate in satellite chlorophyll at low concentrations in 2012 (AMT22), likely due to a small bias in satellite remote-sensing reflectance data. Our results highlight the benefits of using underway spectrophotometric systems for evaluating satellite ocean-colour data and underline the importance of maintaining in situ observatories that sample the oligotrophic gyres.

Underway spectrophotometry along the Atlantic Meridional Transect reveals high performance in satellite chlorophyll retrievals

To evaluate the performance of ocean-colour retrievals of total chlorophyll-a concentration requires direct comparison with concomitant and co-located in situ data. For global comparisons, these in situ match-ups should be ideally representative of the distribution of total chlorophyll-a concentration in the global ocean. The oligotrophic gyres constitute the majority of oceanic water, yet are under-sampled due to their inaccessibility and under-represented in global in situ databases. The Atlantic Meridional Transect (AMT) is one of only a few programmes that consistently sample oligotrophic waters. In this paper, we used a spectrophotometer on two AMT cruises (AMT19 and AMT22) to continuously measure absorption by particles in the water of the ship's flow-through system. From these optical data continuous total chlorophyll-a concentrations were estimated with high precision and accuracy along each cruise and used to evaluate the performance of ocean-colour algorithms. We conducted the evaluation using level 3 binned ocean-colour products, and used the high spatial and temporal resolution of the underway system to maximise the number of match-ups on each cruise. Statistical comparisons show a significant improvement in the performance of satellite chlorophyll algorithms over previous studies, with root mean square errors on average less than half (~ 0.16 in log10 space) that reported previously using global datasets (~ 0.34 in log10 space). This improved performance is likely due to the use of continuous absorption-based chlorophyll estimates, that are highly accurate, sample spatial scales more comparable with satellite pixels, and minimise human errors. Previous comparisons might have reported higher errors due to regional biases in datasets and methodological inconsistencies between investigators. Furthermore, our comparison showed an underestimate in satellite chlorophyll at low concentrations in 2012 (AMT22), likely due to a small bias in satellite remote-sensing reflectance data. Our results highlight the benefits of using underway spectrophotometric systems for evaluating satellite ocean-colour data and underline the importance of maintaining in situ observatories that sample the oligotrophic gyres.

Molecular characteristics and gene segment usage in IGH gene rearrangements in multiple myeloma.

BACKGROUND AND OBJECTIVES: Analysis of IgH rearrangements in B-cell malignancies has provided clinical researchers with a wide range of information during the last few years. However, only a few studies have contributed to the characterization of these features in multiple myeloma (MM), and they have been focused on the analysis of the expressed IgH allele only. Comparison between the expressed and the non-functional IgH alleles allows further characterizion of the selection processes to which pre-myeloma cells are submitted. DESIGN AND METHODS: We analyzed a cohort of 84 untreated MM patients in order to characterize their functional VDJH and non-functional DJH rearrangements. The pattern of mutations and gene segment usage for both types of rearrangements was analyzed by polymerase chain reaction and sequencing. RESULTS: VH3 and VH1 family members were over- and under-represented, respectively. VH3-30 and VH3-15 segments were the most frequently used, whereas VH4-34 was found only in non-functional or heavily mutated VDJH rearrangements. DH2 and DH3 family members were over-represented in both VDJH and DJH repertoires, while the DH1 family was under-represented only in the productive VDJH rearrangements. Finally, DH3-22 and DH2-21 gene segments were found to be over-represented in the functional repertoire while segments commonly used by less mature B-cell malignancies, such as DH6-19 or DH3-3, were under-represented. INTERPRETATION AND CONCLUSIONS: Data reported here help to identify the clonogenic MM cell as a post-germinal center B cell that has undergone selection processes during the germinal center reaction.

Analyzing Gene Centres with the Help of the Checklist Method – the Case of Syria

The present survey of species diversity of cultivated plants is the first for Syria. Some cultivated species will be added in the future, because due to the civil war in Syria, it was not possible to visit the country in the frame of the present work, as initially planned. Checklists proved to be a useful tool for overviewing the cultivated plants of selected areas and allow a characterization of the state of plant genetic resources of Syria. Syria has experienced several civilizations. Man settled in this productive land since ancient times and used its resources. However, such use has led to changes in vegetation and decline of wildlife through the country, in seashore areas, interior, mountains, and grassland. Plant domestication and growing started more than 10,000 years ago in West Asia. Since then, plentiful of economic plant species were present and used by man and his domesticated animals. Forming a part of the Fertile Crescent, where many of the world’s agricultural plants have evolved, Syria is extremely rich in agrobiodiversity. Wild progenitors of wheat and barley and wild relatives of many fruit trees such as almonds and pistachio as well as forage species are still found in marginal lands and less disturbed areas. These are threatened by a wide range of human activities, notably modern, extensive agriculture, overgrazing, overcutting and urban expansion. Syria is also considered as part of one of the main centres of origin, according to Vavilov, who had collected in Syria in 1926. The first expeditions to crop fields showed the exclusive nature of cultivated plants in Syria with a high number of endemic forms. Furthermore, Syria is a part of a biodiversity hotspot. Several studies have been performed to study agrobiodiversity in different parts of Syria, but usually on wild species. Many collections have been carried out; however, they focussed preferably on cereals and pulses, and particularly on wheat, like Vavilov’s expedition. Only 30 crops make up the major part of the conserved Syrian crop plant material in the genebank, indicating that most of the remaining 7,000 species of cultivated plants and many other valuable genetic resources species have only been included on a limited scale in the genebank collections. Although a small country (185,180 km2), Syria accommodates numerous ecosystems that allow for a large diversity of plant genetic resources for agriculture ranging from cold-requiring to subtropical crops to live and thrive. Only few references are available in this respect. The aim of the present study was to complete a checklist of Syria’s cultivated plants of agriculture and horticulture excluding plants only grown as ornamental or for forestry. Furthermore, plants taken for reforestation have not been included, if they do not have also agricultural or horticultural uses. Therefore, the inclusion of plants into the checklist follows the same principles as “Mansfeld’s Encyclopedia”. Main sources of information were published literature, floras of Syria, Lebanon and the Mediterranean, as well as Syrian printed sources in Arabic and/or English, reports from FAO on agricultural statistics in Syria, and data from ICARDA and Bioversity International. In addition, personal observations gathered during professional work in the General Commission for Scientific Agricultural Research (GCSAR) in Syria (since 1989) and participation in projects were taken into account. These were: (1) A project on “Conservation and Sustainable Use of Dry Land Agrobiodiversity in the Near East” with participation of Jordan, Lebanon, Syria, and the Palestinian Authority, focussing on landraces and wild relatives of barley, wheat, lentil, alliums, feed legumes, and fruit trees (1999–2005). (2) A project for vegetable landraces (1993–1995) in collaboration with the former International Plant Genetic Resources Institute and the UN Development Programme, in which 380 local vegetable accessions were evaluated. For medicinal plants and fruit trees I was in personal contact with departments of GCSAR and the Ministry of Agriculture and Agrarian Reform, as well as with private organizations. The resulting checklist was compared with the catalogues of crop plants of Italy and a checklist of cultivated plants of Iraq. The cultivated plant species are presented in alphabetical order according to their accepted scientific names. Each entry consists of a nomenclatural part, folk names, details of plant uses, the distribution in Syria (by provinces), a textual description, and references to literature. In total, 262 species belonging to 146 genera and 57 families were identified. Within-species (intraspecific) diversity is a significant measure of the biodiversity. Intraspecific diversity for wild plants has been and remains to be well studied, but for crop plants there are only few results. Mansfeld’s method is an actual logical contribution to such studies. Among the families, the following have the highest number of crop species: Leguminosae (34 spp.), Rosaceae (24), Gramineae (18), Labiatae (18), Compositae (14), Cruciferae (14), Cucurbitaceae (11), Rutaceae (10), Malvaceae (9), Alliaceae (7), and Anacardiaceae (7). The establishment of an effective programme for the maintenance of plant genetic resources in Syria started in the mid-1970s. This programme considered ex situ and in situ collection of the genetic resources of various field crops, fruit trees and vegetables. From a plant genetic resources viewpoint, it is clear that the homegarden is an important location for the cultivation of so-called neglected and underutilized species (neglected from a research side and underutilized from a larger economic side). Such species have so far not received much care from ecologists, botanists and agronomists, and they are considerably under-represented in genebanks.

Key determinants of organisational silence for non-standard workers

Purpose – The purpose of this paper is to identify the key determinants of organisational silence from the perspective of non-standard workers (NSWs). The study focuses on three research themes: first, analysing the experiences motivating NSWs to remain silent; second, analysing the role of the NSW life cycle in the motivation to remain silent, the final theme is evaluation of the impact on organisational voice of an organisation employing a workforce in which NSWs and standard workers (SWs) are blended. Design/methodology/approach – The study utilises a phenomenological approach, as defined by Van Manen (2007), to collect and analyse the phenomenon of organisational silence from the perspective of NSWs. The NSWs are defined as individuals operating via Limited Liability UK registered companies created for the purpose of delivering services to organisations via a contract of services. This study employed a combination of phenomenology and hermeneutics to collect and analyse the data collected from the NSWs using semi-structured interviews (Lindseth and Norberg, 2004). Findings – The study concludes with three core findings. NSWs experience similar motivational factors to silence as experienced by standard workers (SWs). The key differential between a SW and a NSW is the role of defensive silence as a dominant motivator for a start-up NSW. The study identified that the reasons for this is that new NSWs are defensive to protect their reputation for any future contract opportunities. In addition, organisations are utilising the low confidence of new start up NSWs to suppress the ability of NSWs to voice. The research indicates how experienced NSWs use the marketing stage of their life cycle to establish voice mechanisms. The study identified that NSWs, fulfiling management and supervisory roles for organisations, are supporting/creating climates of silence through their transfer of experiences as SWs prior to becoming NSWs. Research limitations/implications – This study is a pilot study, and the findings from this study will be carried forward into a larger scale study through engagement with further participants across a diverse range of sectors. This study has identified that there is a need for further studies on organisational silence and NSWs to analyse more fully the impact of silence on the individuals and the organisation itself. A qualitative phenomenological hermeneutical study is not intended to be extrapolated to provide broad trends. The focus of the phenomenological hermeneutic research methodology is on describing and analysing the richness and depth of the NSW’s experiences of silence in organisational settings. Originality/value – This paper draws together the studies of worker classification, motivators for organisational silence, and the impact of blending SWs and NSWs in an organisational setting. The study demonstrates that academic research to date has focused predominantly on SWs to the exclusion of the 1.5 million, and growing, NSWs in the UK. This study examines these under-represented workers to analyse the participants’ experiences of organisational silence, and its consequences in organisational settings, demonstrating a need for further studies.

We're offering true play-based learning: teacher perspectives on educational dis/continuity in the early years

Educational continuity is a well-documented challenge facing the early childhood field. This research project investigated preschool and primary teachers' perspectives of educational dis/continuity, as they have been under-represented in the literature to date. The inclusion of dual-qualified educators in the sample group provided the counter-perspective of those who have trained and taught in both settings. It was found that teacher perceptions of how preschool and primary school differentiate have historical roots, and are orientated in the belief that the two settings apply incongruent approaches to teaching and learning. It was argued that gaining knowledge and experience in both settings could open up teachers' perceptions and assist them to find opportunities for improving continuity.

The geo-historical legacies of urban security governance and the Vancouver 2010 Olympics

In 2004, the discourse of ‘legacy’ was woven into the constitutional fabric of the International Olympic Committee (IOC). Bidding for Olympic events is now premised on procuring post-event legacies that will resonate through local communities and host countries long after the flame is extinguished. Given vast expenditures in security, policing, and emergency management operations at major sporting events, it is notable that the IOC and its official partners have disproportionately under-represented security and policing legacies. This paper addresses research into security and policing legacies of major events by turning much needed empirical attention towards institutional level geographies of security and policing – particularly on legacies of policing and militarisation in Olympic host cities. Accordingly, the paper traces the institutional trajectory of the Military Liaison Unit (MLU) in the Vancouver Police Department who were heavily involved in coordinating the joint civilian–military effort throughout the lifecycle of the Vancouver 2010 inter Games. Theoretically, the paper furthers Stephen Graham’s (2010) New Military Urbanism that considers the circulation of military expertise between neo-colonial frontiers of military intervention with Western urban spaces. In doing so, this paper unpacks an empirically guided temporal approach that discerns key drivers of militarisation as localised, empirical-based ‘trajectories’ of development of security and policing institutions, which are linked to, and circumscribed by, critical juncture episodes in the context of mega event security. The paper traces processes of the MLU to explain how conditions underpinning the civil–military divide in urban policing, as a series of jurisdictional, institutional, and by extension, geographical configurations have continued, changed or been abandoned in the context of the Vancouver 2010 Olympics. As such, this paper contributes to much needed debate on the controversies and opportunities inherent in security legacies and major events, which implicate the wider securitisation and militarisation of Western cities.