New insights into probiotic mechanisms: a harvest from functional and metagenomic studies

There has been continued and expanding recognition of probiotic approaches for treating gastrointestinal and systemic disease, as well as increased acceptance of probiotic therapies by both the public and the medical community. A parallel development has been the increasing recognition of the diverse roles that the normal gut microbiota plays in the normal biology of the host. This advance has in turn has been fed by implementation of novel investigative technologies and conceptual paradigms focused on understanding the fundamental role of the microbiota and indeed all commensal bacteria, on known and previously unsuspected aspects of host physiology in health and disease. This review discusses current advances in the study of the host-microbiota interaction, especially as it relates to potential mechanisms of probiotics. It is hoped these new approaches will allow more rational selection and validation of probiotic usage in a variety of clinical conditions.

Student teachers’ perceptions of reading and the teaching of reading: the implications for teacher education

This article reports on research which identified perceptions of reading and the teaching of reading held by trainee teachers and the impact on my provision as a teacher educator. It found that students’ past and present experiences of learning to read and being a reader influenced their perceptions of what reading is and of what it means to teach reading. As a teacher educator, I am not able to give students long experience of seeing children becoming readers, but I am able to give them richer experiences of reading in personally and culturally relevant contexts. This has implications for the nature of subject knowledge required by a student teacher of reading and the curriculum and practice of teacher education.

Insights into dietary flavonoids as molecular templates for the design of anti-platelet drugs

Flavonoids are low-molecular weight, aromatic compounds derived from fruits, vegetables, and other plant components. The consumption of these phytochemicals has been reported to be associated with reduced cardiovascular disease (CVD) risk, attributed to their anti-inflammatory, anti-proliferative, and anti-thrombotic actions. Flavonoids exert these effects by a number of mechanisms which include attenuation of kinase activity mediated at the cell-receptor level and/or within cells, and are characterized as broad-spectrum kinase inhibitors. Therefore, flavonoid therapy for CVD is potentially complex; the use of these compounds as molecular templates for the design of selective and potent small-molecule inhibitors may be a simpler approach to treat this condition. Flavonoids as templates for drug design are, however, poorly exploited despite the development of analogues based on the flavonol, isoflavonone, and isoflavanone subgroups. Further exploitation of this family of compounds is warranted due to a structural diversity that presents great scope for creating novel kinase inhibitors. The use of computational methodologies to define the flavonoid pharmacophore together with biological investigations of their effects on kinase activity, in appropriate cellular systems, is the current approach to characterize key structural features that will inform drug design. This focussed review highlights the potential of flavonoids to guide the design of clinically safer, more selective, and potent small-molecule inhibitors of cell signalling, applicable to anti-platelet therapy.

Impression management, myth creation and fabrication in private social and environmental reporting: insights from Erving Goffman

This paper explores the nature of private social and environmental reporting (SER). From interviews with UK institutional investors, we show that both investors and investees employ Goffmanesque, staged impression management as a means of creating and disseminating a dual myth of social and environmental accountability. The interviewees’ utterances unveil private meetings imbued with theatrical verbal and physical impression management. Most of the time, the investors’ shared awareness of reality belongs to a Goffmanesque frame whereby they accept no intentionality, misrepresentation or fabrication, believing instead that the ‘performers’ (investees) are not intending to deceive them. A shared perception that social and environmental considerations are subordinated to financial issues renders private SER an empty encounter characterised as a relationship-building exercise with seldom any impact on investment decision-making. Investors spoke of occasional instances of fabrication but these were insufficient to break the frame of dual myth creation. They only identified a handful of instances where intentional misrepresentation had been significant enough to alter their reality and behaviour. Only in the most extreme cases of fabrication and lying did the staged meeting break frame and become a genuine occasion of accountability, where investors demanded greater transparency, further meetings and at the extreme, divested shares. We conclude that the frontstage, ritualistic impression management in private SER is inconsistent with backstage activities within financial institutions where private financial reporting is prioritised. The investors appeared to be in a double bind whereby they devoted resources to private SER but were simultaneously aware that these efforts may be at best subordinated, at worst ignored, rendering private SER a predominantly cosmetic, theatrical and empty exercise.

Population based models of cortical drug response: insights from anaesthesia

A great explanatory gap lies between the molecular pharmacology of psychoactive agents and the neurophysiological changes they induce, as recorded by neuroimaging modalities. Causally relating the cellular actions of psychoactive compounds to their influence on population activity is experimentally challenging. Recent developments in the dynamical modelling of neural tissue have attempted to span this explanatory gap between microscopic targets and their macroscopic neurophysiological effects via a range of biologically plausible dynamical models of cortical tissue. Such theoretical models allow exploration of neural dynamics, in particular their modification by drug action. The ability to theoretically bridge scales is due to a biologically plausible averaging of cortical tissue properties. In the resulting macroscopic neural field, individual neurons need not be explicitly represented (as in neural networks). The following paper aims to provide a non-technical introduction to the mean field population modelling of drug action and its recent successes in modelling anaesthesia.

Controlling spurious diapycnal mixing in eddy-resolving height-coordinate ocean models: insights from virtual deliberate tracer release experiments

A perceived limitation of z-coordinate models associated with spurious diapycnal mixing in eddying, frontal flow, can be readily addressed through appropriate attention to the tracer advection schemes employed. It is demonstrated that tracer advection schemes developed by Prather and collaborators for application in the stratosphere, greatly improve the fidelity of eddying flows, reducing levels of spurious diapycnal mixing to below those directly measured in field experiments, ∼1 × 10−5 m2 s−1. This approach yields a model in which geostrophic eddies are quasi-adiabatic in the ocean interior, so that the residual-mean overturning circulation aligns almost perfectly with density contours. A reentrant channel configuration of the MIT General Circulation Model, that approximates the Antarctic Circumpolar Current, is used to examine these issues. Virtual analogs of ocean deliberate tracer release field experiments reinforce our conclusion, producing passive tracer solutions that parallel field experiments remarkably well.

Impression management, fabrication and myth creation in private social and environmental reporting: insights from Erving Goffman

This paper explores the nature of private social and environmental reporting (SER). From interviews with UK institutional investors, we show that both investors and investees employ Goffmanesque, staged impression management as a means of creating and disseminating a dual myth of social and environmental accountability. The interviewees’ utterances unveil private meetings imbued with theatrical verbal and physical impression management. Most of the time, the investors’ shared awareness of reality belongs to a Goffmanesque frame whereby they accept no intentionality, misrepresentation or fabrication, believing instead that the ‘performers’ (investees) are not intending to deceive them. A shared perception that social and environmental considerations are subordinated to financial issues renders private SER an empty encounter characterised as a relationship-building exercise with seldom any impact on investment decision-making. Investors spoke of occasional instances of fabrication but these were insufficient to break the frame of dual myth creation. They only identified a handful of instances where intentional misrepresentation had been significant enough to alter their reality and behaviour. Only in the most extreme cases of fabrication and lying did the staged meeting break frame and become a genuine occasion of accountability, where investors demanded greater transparency, further meetings and at the extreme, divested shares. We conclude that the frontstage, ritualistic impression management in private SER is inconsistent with backstage activities within financial institutions where private financial reporting is prioritised. The investors appeared to be in a double bind whereby they devoted resources to private SER but were simultaneously aware that these efforts may be at best subordinated, at worst ignored, rendering private SER a predominantly cosmetic, theatrical and empty exercise.

Insights into the molecular architecture of a peptide nanotube using FTIR and solid-state NMR spectroscopic measurements on an aligned sample

The self-assembly of proteins and peptides into b-sheet-rich amyloid fibers is a process that has gained notoriety because of its association with human diseases and disorders. Spontaneous self-assembly of peptides into nonfibrillar supramolecular structures can also provide a versatile and convenient mechanism for the bottom-up design of biocompatible materials with functional properties favoring a wide range of practical applications.[1] One subset of these fascinating and potentially useful nanoscale constructions are the peptide nanotubes, elongated cylindrical structures with a hollow center bounded by a thin wall of peptide molecules.[2] A formidable challenge in optimizing and harnessing the properties of nanotube assemblies is to gain atomistic insight into their architecture, and to elucidate precisely how the tubular morphology is constructed from the peptide building blocks. Some of these fine details have been elucidated recently with the use of magic-angle-spinning (MAS) solidstate NMR (SSNMR) spectroscopy.[3] MAS SSNMR measurements of chemical shifts and through-space interatomic distances provide constraints on peptide conformation (e.g., b-strands and turns) and quaternary packing. We describe here a new application of a straightforward SSNMR technique which, when combined with FTIR spectroscopy, reports quantitatively on the orientation of the peptide molecules within the nanotube structure, thereby providing an additional structural constraint not accessible to MAS SSNMR.

Molecular insights into aggregates made of amphiphilic Fmoc-tetrapeptides

Pre-assembled aggregates made of Fmoc-conjugated RGDS and GRDS peptides, where Fmoc refers to fluorenylmethoxycarbonyl, have been investigated using atomistic molecular dynamics simulations. The structural characteristics of twelve different models involving two sheets packed with the Fmoc-aligned or with the charged side groups oriented face-to-face, each one containing seven explicit peptide molecules arranged in parallel or antiparallel, have been evaluated for each Fmoc-tetrapeptide. Structural criteria have been used to select the preferred assembly for each Fmoc-tetrapeptide. The two peptides have been found to prefer b-sheet assemblies with a parallel configuration under simulated low concentration conditions. Furthermore, the assembly is dominated by the interactions among Fmoc units. The overall results provide a complete atomistic view of the interactions between Fmoc-peptide molecules comprised within the same sheet or in different sheets that was not achieved experimentally.

Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex-vivo cytokine production – insights from the SATgenε study

Apolipoprotein E (APOE) genotype is believed to play an important role in cardiovascular risk. APOE4 carriers have been associated with higher blood lipid levels and a more pro-inflammatory state compared with APOE3/E3 individuals. Although dietary fat composition has been considered to modulate the inflammatory state in humans, very little is known about how APOE genotype can impact on this response. In a follow-up to the main SATgene study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. Blood samples were collected from a subset of SATgene participants (n = 52/88), prospectively recruited according to APOE genotype (n = 26 E3/E3 and n = 26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45 g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24 h with either 0.05 or 1 lg/ml of bacterial lipopolysaccharide (LPS). Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-a and IL-10 production; TNF-a concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P < 0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P < 0.05). In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-a and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects.

Teacher stance as reflected in feedback on student writing: An empirical study of secondary school teachers in five countries

This study examines the feedback practices of 110 EFL teachers from five different countries (Cyprus, France, Korea, Spain, and Thailand), working in secondary school contexts. All provided feedback on the same student essay. The coding scheme developed to analyse the feedback operates on two axes: the stance the teachers assumed when providing feedback, and the focus of their feedback. Most teachers reacted as language teachers, rather than as readers of communication. The teachers overwhelmingly focused on grammar in their feedback and assumed what we called a Provider role, providing the correct forms for the student. A second role, Initiator, was also present, in which teachers indicate errors or issues to the learner but expect the learner to pick this up and work on it. This role was associated with a more even spread of feedback focus, where teachers also provided feedback on other areas, such as lexis, style and discourse.

Teacher beliefs about listening in a foreign language

This study investigated, through a questionnaire, the stated beliefs and stated practices of 115 foreign language teachers in England regarding listening pedagogy: whether such beliefs and practices reflect the literature on listening, whether beliefs and stated practices converged, and what factors might underpin them. Responses indicated a mismatch between teachers’ stated belief in the importance of teaching learners how to listen more effectively, and the lack of evidence in their stated practice of such teaching, with a focus instead on task completion. Findings are discussed against the accountability agenda of the study’s context, and its implications for teacher development highlighted.

Genetic, structural, and molecular insights into the function of ras of complex proteins domains

Ras of complex proteins (ROC) domains were identified in 2003 as GTP binding modules in large multidomain proteins from Dictyostelium discoideum. Research into the function of these domains exploded with their identification in a number of proteins linked to human disease, including leucine-rich repeat kinase 2 (LRRK2) and death-associated protein kinase 1 (DAPK1) in Parkinson’s disease and cancer, respectively. This surge in research has resulted in a growing body of data revealing the role that ROC domains play in regulating protein function and signaling pathways. In this review, recent advances in the structural informa- tion available for proteins containing ROC domains, along with insights into enzymatic function and the integration of ROC domains as molecular switches in a cellular and organismal context, are explored.