Epstein-Barr Virus Large Tegument Protein BPLF1 Contributes to Innate Immune Evasion through Interference with Toll-Like Receptor Signaling

Viral infection triggers an early host response through activation of pattern recognition receptors, including Toll-like receptors (TLR). TLR signaling cascades induce production of type I interferons and proinflammatory cytokines involved in establishing an anti-viral state as well as in orchestrating ensuing adaptive immunity. To allow infection, replication, and persistence, (herpes)viruses employ ingenious strategies to evade host immunity. The human gamma-herpesvirus Epstein-Barr virus (EBV) is a large, enveloped DNA virus persistently carried by more than 90% of adults worldwide. It is the causative agent of infectious mononucleosis and is associated with several malignant tumors. EBV activates TLRs, including TLR2, TLR3, and TLR9. Interestingly, both the expression of and signaling by TLRs is attenuated during productive EBV infection. Ubiquitination plays an important role in regulating TLR signaling and is controlled by ubiquitin ligases and deubiquitinases (DUBs). The EBV genome encodes three proteins reported to exert in vitro deubiquitinase activity. Using active site-directed probes, we show that one of these putative DUBs, the conserved herpesvirus large tegument protein BPLF1, acts as a functional DUB in EBV-producing B cells. The BPLF1 enzyme is expressed during the late phase of lytic EBV infection and is incorporated into viral particles. The N-terminal part of the large BPLF1 protein contains the catalytic site for DUB activity and suppresses TLR-mediated activation of NF-κB at, or downstream of, the TRAF6 signaling intermediate. A catalytically inactive mutant of this EBV protein did not reduce NF-κB activation, indicating that DUB activity is essential for attenuating TLR signal transduction. Our combined results show that EBV employs deubiquitination of signaling intermediates in the TLR cascade as a mechanism to counteract innate anti-viral immunity of infected hosts.

Ecopoetics: The Language of Nature, The Nature of Language by Scott Knickerbocker (review)

Review of Ecopoetics: The Language of Nature, The Nature of Language by Scott Knickerbocker Boston: University of Massachusetts Press, 2012. Pp. x + 203.
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Patient safety and communication: A new assessment for doctors trained in countries where language differs from that of the host country: Results of a pilot using a domain-based assessment

Objective

Global migration of healthcare workers places responsibility on employers to comply with legal employment rights whilst ensuring patient safety remains the central goal. We describe the pilot of a communication assessment designed for doctors who trained and communicated with patients and colleagues in a different language from that of the host country. It is unique in assessing clinical communication without assessing knowledge.

A 14-station OSCE was developed using a domain-based marking scheme, covering professional communication and English language skills (speaking, listening, reading and writing) in routine, acute and emotionally challenging contexts, with patients, carers and healthcare teams. Candidates (n = 43), non-UK trained volunteers applying to the UK Foundation Programme, were provided with relevant station information prior to the exam.

The criteria for passing the test included achieving the pass score and passing 10 or more of the 14 stations. Of the 43 candidates, nine failed on the station criteria. Two failed the pass score and also the station criteria. The Cronbach's alpha coefficient was 0.866.

This pilot tested ‘proof of concept’ of a new domain-based communication assessment for non-UK trained doctors.

The test would enable employers and regulators to verify communication competence and safety in clinical contexts, independent of clinical knowledge, for doctors who trained in a language different from that of the host country.

Proactive Relay Selection with Joint Impact of Hardware Impairment and Co-channel Interference

In this paper, we investigate the end-to-end performance of dual-hop proactive decode-and-forward relaying networks with Nth best relay selection in the presence of two practical deleterious effects: i) hardware impairment and ii) cochannel interference. In particular, we derive new exact and asymptotic closed-form expressions for the outage probability and average channel capacity of Nth best partial and opportunistic relay selection schemes over Rayleigh fading channels. Insightful discussions are provided. It is shown that, when the system cannot select the best relay for cooperation, the partial relay selection scheme outperforms the opportunistic method under the impact of the same co-channel interference (CCI). In addition, without CCI but under the effect of hardware impairment, it is shown that both selection strategies have the same asymptotic channel capacity. Monte Carlo simulations are presented to corroborate our analysis.

Parent ratings of child cognition and language compared with Bayley-III in preterm 3-year-olds

Background
Parent ratings on questionnaires may provide valid and cost-effective tools for screening cognitive development of children at risk of developmental delay.

Aims
In this study, we examined the convergent validity of combining parent-based reports of non-verbal cognitive abilities (PARCA3) and verbal abilities (CDI-III) in relation to the Bayley-III cognitive scale in 3-year-olds born late pre-term.

Methods
Mothers of 185 late-preterm children were asked to complete the PARCA3 and the CDI-III shortly before children reached age three; children were then assessed using the Bayley-III close to their third birthday.

Results
The two maternal questionnaires were significantly and moderately correlated with the Bayley-III cognitive scores. Together the maternal ratings accounted for 15% of the variance in the Bayley-III cognitive scores, after controlling for other covariates in regression analysis. In particular, the PARCA3 contributed significantly to explain variance in the Bayley-III cognitive scores when controlling for the CDI-III. However, the CDI-III was also independently associated with the Bayley-III cognitive scores.

Conclusions
Parent ratings of child cognition and language together may provide cost-effective screening of development in “at risk” preschoolers.

Neural basis of language switching in the brain: fMRI evidence from Korean-Chinese early bilinguals

Using fMRI, we conducted two types of property generation task that involved language switching, with early bilingual speakers of Korean and Chinese. The first is a more conventional task in which a single language (L1 or L2) was used within each trial, but switched randomly from trial to trial. The other consists of a novel experimental design where language switching happens within each trial, alternating in the direction of the L1/L2 translation required. Our findings support a recently introduced cognitive model, the 'hodological' view of language switching proposed by Moritz-Gasser and Duffau. The nodes of a distributed neural network that this model proposes are consistent with the informative regions that we extracted in this study, using both GLM methods and Multivariate Pattern Analyses: the supplementary motor area, caudate, supramarginal gyrus and fusiform gyrus and other cortical areas. 

English Language Education at University: Trends and Challenges in Teaching and Learning Academic Discourse in the UK

This chapter discusses English Language Education at university and highlights a number of trends and their associated challenges in teaching and learning academic discourse. Academic discourse refers to the ways in which language is used by participants in academia. It encompasses written discourse, from article and book publishing, PhD theses to course assignments; spoken discourse, from study groups, tutorials, conference presentations to inaugural lectures; and more recently, computer-mediated discourse, from asynchronous text-based conferencing to academic blogs. The role of English language educators in preparing students and academics for successful participation in these academic events, or the academy, in English is not to be underestimated. Academic communication is not only vital to an individual’s success at university, but to the maintenance and creation of academic communities and to scientific progress itself (Hyland, 2009). This chapter presents an overview of academic discourse and discusses recent issues which have an impact on teaching and learning English at university and discusses their associated challenges: first, the increasing internationalisation of universities. Second, the emergence of a mobile academe in its broadest sense, in which students and academics move across traditional geopolitical, institutional and disciplinary boundaries, is discussed. Third, the growth of UK transnational higher education is examined as a trend which sees academics and students vicariously or otherwise involved in English language teaching and learning. Fourth, the chapter delves into the rapid and ongoing development in technology assisted and online learning. While responding to trends can be difficult, they can also inspire ingenuity. Furthermore, such trends and challenges will not emerge in the same manner in different contexts. The discussion in this chapter is illustrated with examples from a UK context but the implications of the trends and challenges are such that they reach beyond borders.

RNA interference in adult Ascaris suum - an opportunity for the development of a functional genomics platform that supports organism-, tissue- and cell-based biology in a nematode parasite

The sustainable control of animal parasitic nematodes requires the development of efficient functional genomics platforms to facilitate target validation and enhance anthelmintic discovery. Unfortunately, the utility of RNA interference (RNAi) for the validation of novel drug targets in nematode parasites remains problematic. Ascaris suum is an important veterinary parasite and a zoonotic pathogen. Here we show that adult A. suum is RNAi competent, and highlight the induction, spread and consistency of RNAi across multiple tissue types. This platform provides a new opportunity to undertake whole organism-, tissue- and cell-level gene function studies to enhance target validation processes for nematode parasites of veterinary/medical significance.