The REACT Collaborative Development Programme: Bringing universities together to enhance student-engagement activities for the ‘hard to reach’

As outlined in the funding application to the Higher Education Funding Council for Engagement (HEFCE), the REACT programme was designed to support the expansion of context-appropriate interventions to at least ten further universities through consultancy, workshops, mentoring of Student Unions and academic staff in other institutions, and working with students and student engagement practitioners to spread the interventions (REACT, 2015). This aligned with other aims of the bid, including that REACT would: disseminate best practice in relation to the challenge of engaging those outside the usual ambit of Student Engagement (SE) activities; build communities of practice based on strong evidence; and provide consultancy support and proven approaches amongst at least ten UK universities.This paper highlights how the REACT Collaborative Development Programme was designed to facilitate these aims, to build momentum and spread practice beyond the core of Winchester, Exeter and London Metropolitan universities. All aspects of the programme are outlined, from the initial Expression of Interest to the collaborative process of putting together this issue of JEIPC as a final output of REACT

Cd2+- or Hg2+-binding proteins can replace the Cu+-chaperone Atx1 in delivering Cu+ to the secretory pathway in yeast

AbstractCopper delivery to Ccc2 – the Golgi Cu+-ATPase – was investigated in vivo, replacing the Cu+-chaperone Atx1 by various structural homologues in an atx1-Δ yeast strain. Various proteins, displaying the same ferredoxin-like fold and (M/L)(T/S)CXXC metal-binding motif as Atx1 and known as Cu+-, Cd2+- or Hg2+-binding proteins were able to replace Atx1. Therefore, regardless of their original function, these proteins could all bind copper and transfer it to Ccc2, suggesting that Ccc2 is opportunistic and can interact with many different proteins to gain Cu+. The possible role of electrostatic potential surfaces in the docking of Ccc2 with these Atx1-homologues is discussed

Upper Elementary and Middle School U.S. Teachers’ Views of Grammar and Its Instruction

The purpose of this study was to investigate upper elementary (Grades 4–6) and middle school (Grades 6–8) teachers’ views of grammar and its instruction and to determine differences in their views about grammar, its instruction, and its importance to writing proficiency. Participants in this online study were 196 practicing teachers in eight school districts in one western U.S. state. Two thirds of the teachers in the study taught at the elementary level, and one third taught at the middle school level. When asked what they taught when teaching grammar, the large majority of these teachers reported teaching parts of speech, punctuation, and sentence structure. Overall, there were few significant differences between upper elementary and middle school teachers in the instructional strategies and curricular materials they reported using, in their views of how important it was to teach various aspects of grammar, and in their views of the extent to which those aspects of grammar improved writing proficiency. Findings are discussed in relation to prior research, and implications are drawn for the field

Realising Engagement through Active Culture Transformation: An Introduction to the REACT Programme

The REACT programme was designed to make a significant impact on student engagement and the student experience in the Higher Education (HE) sector in England and Wales over a two-year period, from July 2015 to July 2017. The focus, in particular, was on the engagement of so-called hard to reach students, and the programme included: investigation into the term hard to reach and a consideration of which students are characterised in this way; a formal research project looking at links between student engagement, retention and attainment; and a development programme as a collaboration between fifteen UK universities. Outcomes from each of these were disseminated at a final conference at the University of Winchester in May 2017, where practice and findings from the programme as a whole were shared. The programme also included the creation of a website of case studies and tools for use by the sector. The programme was funded by the Higher Education Funding Council for England (HEFCE) and was formally evaluated by an external team from GuildHE

Glycan processing in gut microbiomes

Microbiomes and their enzymes process many of the nutrients accessible in the gastrointestinal tract of bilaterians and play an essential role in host health and nutrition. In this review, we describe recent insights into nutrient processing in microbiomes across three exemplary yet contrasting gastrointestinal ecosystems (humans, ruminants and insects), with focus on bacterial mechanisms for the utilization of common and atypical dietary glycans as well as host-derived mucus glycans. In parallel, we discuss findings from multi-omic studies that have provided new perspectives on understanding glycan-dependent interactions and the complex food-webs of microbial populations in their natural habitat. Using key examples, we emphasize how increasing understanding of glycan processing by gut microbiomes can provide critical insights to assist ‘microbiome reprogramming’, a growing field that seeks to leverage diet to improve animal growth and host health

How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans

The human microbiota, which plays an important role in health and disease, uses complex carbohydrates as a major source of nutrients. Utilization hierarchy indicates that the host glycosaminoglycans heparin (Hep) and heparan sulfate (HS) are high-priority carbohydrates for Bacteroides thetaiotaomicron, a prominent member of the human microbiota. The sulfation patterns of these glycosaminoglycans are highly variable, which presents a significant enzymatic challenge to the polysaccharide lyases and sulfatases that mediate degradation. It is possible that the bacterium recruits lyases with highly plastic specificities and expresses a repertoire of enzymes that target substructures of the glycosaminoglycans with variable sulfation or that the glycans are desulfated before cleavage by the lyases. To distinguish between these mechanisms, the components of the B. thetaiotaomicron Hep/HS degrading apparatus were analyzed. The data showed that the bacterium expressed a single-surface endo-acting lyase that cleaved HS, reflecting its higher molecular weight compared with Hep. Both Hep and HS oligosaccharides imported into the periplasm were degraded by a repertoire of lyases, with each enzyme displaying specificity for substructures within these glycosaminoglycans that display a different degree of sulfation. Furthermore, the crystal structures of a key surface glycan binding protein, which is able to bind both Hep and HS, and periplasmic sulfatases reveal the major specificity determinants for these proteins. The locus described here is highly conserved within the human gut Bacteroides, indicating that the model developed is of generic relevance to this important microbial community

Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism

Yeasts, which have been a component of the human diet for at least 7000 years, possess an elaborate cell wall α-mannan. The influence of yeast mannan on the ecology of the human microbiota is unknown. Here we show that yeast α-mannan is a viable food source for Bacteroides thetaiotaomicron (Bt), a dominant member of the microbiota. Detailed biochemical analysis and targeted gene disruption studies support a model whereby limited cleavage of α-mannan on the surface generates large oligosaccharides that are subsequently depolymerized to mannose by the action of periplasmic enzymes. Co-culturing studies showed that metabolism of yeast mannan by Bt presents a ‘selfish’ model for the catabolism of this recalcitrant polysaccharide. This report shows how a cohort of highly successful members of the microbiota has evolved to consume sterically-restricted yeast glycans, an adaptation that may reflect the incorporation of eukaryotic microorganisms into the human diet

Stage-Specific Inhibition of MHC Class I Presentation by the Epstein-Barr Virus BNLF2a Protein during Virus Lytic Cycle

gamma-herpesvirus Epstein-Barr virus (EBV) persists for life in infected individuals despite the presence of a strong immune response. During the lytic cycle of EBV many viral proteins are expressed, potentially allowing virally infected cells to be recognized and eliminated by CD8+ T cells. We have recently identified an immune evasion protein encoded by EBV, BNLF2a, which is expressed in early phase lytic replication and inhibits peptide- and ATP-binding functions of the transporter associated with antigen processing. Ectopic expression of BNLF2a causes decreased surface MHC class I expression and inhibits the presentation of indicator antigens to CD8+ T cells. Here we sought to examine the influence of BNLF2a when expressed naturally during EBV lytic replication. We generated a BNLF2a-deleted recombinant EBV (ΔBNLF2a) and compared the ability of ΔBNLF2a and wild-type EBV-transformed B cell lines to be recognized by CD8+ T cell clones specific for EBV-encoded immediate early, early and late lytic antigens. Epitopes derived from immediate early and early expressed proteins were better recognized when presented by ΔBNLF2a transformed cells compared to wild-type virus transformants. However, recognition of late antigens by CD8+ T cells remained equally poor when presented by both wild-type and ΔBNLF2a cell targets. Analysis of BNLF2a and target protein expression kinetics showed that although BNLF2a is expressed during early phase replication, it is expressed at a time when there is an upregulation of immediate early proteins and initiation of early protein synthesis. Interestingly, BNLF2a protein expression was found to be lost by late lytic cycle yet ΔBNLF2a-transformed cells in late stage replication downregulated surface MHC class I to a similar extent as wild-type EBV-transformed cells. These data show that BNLF2a-mediated expression is stage-specific, affecting presentation of immediate early and early proteins, and that other evasion mechanisms operate later in the lytic cycle

Glycan complexity dictates microbial resource allocation in the large intestine.

The structure of the human gut microbiota is controlled primarily through the degradation of complex dietary carbohydrates, but the extent to which carbohydrate breakdown products are shared between members of the microbiota is unclear. We show here, using xylan as a model, that sharing the breakdown products of complex carbohydrates by key members of the microbiota, such as Bacteroides ovatus, is dependent on the complexity of the target glycan. Characterization of the extensive xylan degrading apparatus expressed by B. ovatus reveals that the breakdown of the polysaccharide by the human gut microbiota is significantly more complex than previous models suggested, which were based on the deconstruction of xylans containing limited monosaccharide side chains. Our report presents a highly complex and dynamic xylan degrading apparatus that is fine-tuned to recognize the different forms of the polysaccharide presented to the human gut microbiota.This work was supported in part by grants to D.N.B. (BBSRC BB/G016186/1) and H.J.G. (Wellcome Trust WT097907AIA).This is the final version. It was first published by NPG at http://dx.doi.org/10.1038/ncomms848

Dietary pectic glycans are degraded by coordinated enzyme pathways in human colonic Bacteroides.

The major nutrients available to human colonic Bacteroides species are glycans, exemplified by pectins, a network of covalently linked plant cell wall polysaccharides containing galacturonic acid (GalA). Metabolism of complex carbohydrates by the Bacteroides genus is orchestrated by polysaccharide utilization loci (PULs). In Bacteroides thetaiotaomicron, a human colonic bacterium, the PULs activated by different pectin domains have been identified; however, the mechanism by which these loci contribute to the degradation of these GalA-containing polysaccharides is poorly understood. Here we show that each PUL orchestrates the metabolism of specific pectin molecules, recruiting enzymes from two previously unknown glycoside hydrolase families. The apparatus that depolymerizes the backbone of rhamnogalacturonan-I is particularly complex. This system contains several glycoside hydrolases that trim the remnants of other pectin domains attached to rhamnogalacturonan-I, and nine enzymes that contribute to the degradation of the backbone that makes up a rhamnose-GalA repeating unit. The catalytic properties of the pectin-degrading enzymes are optimized to protect the glycan cues that activate the specific PULs ensuring a continuous supply of inducing molecules throughout growth. The contribution of Bacteroides spp. to metabolism of the pectic network is illustrated by cross-feeding between organisms.This work was supported in part by an Advanced Grant from the European Research Council (Grant No. 322820) awarded to H.J.G. and B.H. supporting A.S.L., D.N., A.C. and N.T., a Wellcome Trust Senior Investigator Award to H.J.G. (grant No. WT097907MA) that supported J.B. and E.C.L. a European Union Seventh Framework Initial Training Network Programme entitled the “WallTraC project” (Grant Agreement number 263916) awarded to M-C.R. and H.J.G, which supported X.Z. and J.S. The Biotechnology and Biological Research Council project ‘Ricefuel’ (grant numbers BB/K020358/1) awarded to H.J.G. supported A.L