Heme oxygenase-1 protects against Alzheimer’s amyloid-β1-42 induced toxicity via carbon monoxide production

Heme oxygenase-1 (HO-1), an inducible enzyme up-regulated in Alzheimer‟s disease (AD), catabolises heme to biliverdin, Fe2+ and carbon monoxide (CO). CO can protect neurones from oxidative stress-induced apoptosis by inhibiting Kv2.1 channels, which mediate cellular K+ efflux as an early step in the apoptotic cascade. Since apoptosis contributes to the neuronal loss associated with amyloid β peptide (Aβ) toxicity in AD, we investigated the protective effects of HO-1 and CO against Aβ1-42 toxicity in SH-SY5Y cells, employing cells stably transfected with empty vector or expressing the cellular prion protein, PrPc, and rat primary hippocampal neurons. Aβ1-42 (containing protofibrils) caused a concentrationdependent decrease in cell viability, attributable at least in part to induction of apoptosis, with the PrPc expressing cells showing greater susceptibility to Aβ1-42 toxicity. Pharmacological induction or genetic over-expression of HO-1 significantly ameliorated the effects of Aβ1-42. The CO-donor CORM-2 protected cells against Aβ1-42 toxicity in a concentration-dependent manner. Electrophysiological studies revealed no differences in the outward current pre- and post-Aβ1-42 treatment suggesting that K+ channel activity is unaffected in these cells. Instead, Aβ toxicity was reduced by the L-type Ca2+ channel blocker nifedipine, and by the CaMKKII inhibitor, STO-609. Aβ also activated the downstream kinase, AMP-dependent protein kinase (AMPK). CO prevented this activation of AMPK. Our findings indicate that HO-1 protects against Aβ toxicity via production of CO. Protection does not arise from inhibition of apoptosis-associated K+ efflux, but rather by inhibition of AMPK activation, which has been recently implicated in the toxic effects of Aβ. These data provide a novel, beneficial effect of CO which adds to its growing potential as a therapeutic agent.

Oxygen-dependent hydroxylation by Factor Inhibiting HIF (FIH) regulates the TRPV3 ion channel

Factor Inhibiting HIF (FIH) is an oxygen-dependent asparaginyl hydroxylase that regulates the hypoxia-inducible factors (HIFs). Several proteins containing ankyrin repeat domains have been characterised as substrates of FIH, although there is little evidence for a functional consequence of hydroxylation on these substrates. This study demonstrates that the transient receptor potential vanilloid 3 (TRPV3) channel is hydroxylated by FIH on asparagine 242 within the cytoplasmic ankyrin repeat domain. Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity. This novel mechanism of channel regulation by oxygendependent asparaginyl hydroxylation is likely to extend to other ion channels.

Early, late or very late? Timing acquisition and bilingualism

Research on child bilingualism accounts for differences in the course and the outcomes of monolingual and different types of bilingual language acquisition primarily from two perspectives: age of onset of exposure to the language(s) and the role of the input (Genesee, Paradis, & Crago, 2004; Meisel, 2009; Unsworth et al., 2014). Some findings suggest that early successive bilingual children may pattern similarly to simultaneous bilingual children, passing through different trajectories from child L2 learners due to a later age of onset in the latter group. Studies on bilingual development have also shown that input quantity in bilingual acquisition is considerably reduced, i.e., in each of their two languages, bilingual children are likely exposed to much less input than their monolingual peers (Paradis & Genesee, 1996; Unsworth, 2013b). At the same time, simultaneous bilingual children develop and attain competence in the two languages, sometimes without even an attested age delay compared to monolingual children (Paradis, Genesee & Crago, 2011). The implication is that even half of the input suffices for early language development, at least with respect to ‘core’ aspects of language, in whatever way ‘core’ is defined.My aim in this article is to consider how an additional, linguistic variable interacts with age of onset and input in bilingual development, namely, the timing in L1 development of the phenomena examined in bilingual children’s performance. Specifically, I will consider timing differences attested in the monolingual development of features and structures, distinguishing between early, late or ‘very late’ acquired phenomena. I will then argue that this three-way distinction reflects differences in the role of narrow syntax: early phenomena are core, parametric and narrowly syntactic, in contrast to late and very late phenomena, which involve syntax-external or even language-external resources too. I explore the consequences of these timing differences in monolingual development for bilingual development. I will review some findings from early (V2 in Germanic, grammatical gender in Greek), late (passives) and very late (grammatical gender in Dutch) phenomena in the bilingual literature and argue that early phenomena can differentiate between simultaneous and (early) successive bilingualism with an advantage for the former group, while the other two reveal similarly (high or low) performance across bilingual groups, differentiating them from monolinguals. The paper proposes that questions about the role of age of onset and language input in early bilingual development can only be meaningfully addressed when the properties and timing of the phenomena under investigation are taken into account.

Do online hotel rating schemes influence booking behaviours?

Travelers’ hotel booking behaviors increasingly depend on peers' opinions and online ratings. This study investigates the effects of online hotel ratings on travelers' attitudes toward the hotel and booking intentions, using a 2 × 2 experimental research design. The results suggest that online rating lists are more useful and credible when published by well-known online travel communities (e.g., TripAdvisor). More favorable attitudes toward a hotel and higher booking intentions emerge when the hotel appears in best hotels lists. Finally, for the entries on best hotels lists, better attitudes and higher booking intentions result if the list is published on a well-known online travel community (Tripadvisor), whereas for entries on a worst hotel list, attitudes and booking intentions decrease even further if the list appears on TripAdvisor.

HIV care and interdependence in Tanzania and Uganda

Within many communities in East Africa, people living with HIV are increasingly involved in delivering home-based care and healthcare for family members and peers. Such interdependent caring relations blur conventional boundaries between ‘care-givers’ and ‘care-recipients’, and constructions of 'service users' as dependent, passive recipients of healthcare. The participation of people living with HIV in healthcare provision, home-based care and peer support groups can enhance ‘relational autonomy’ for both care-givers and care-recipients, although such initiatives often play out in highly gendered ways. The care and support of people living with HIV, particularly the emotion work of caring, however, continues to be associated with women's and girls' assumed 'natural' nurturing roles and has been largely devalued and overlooked in HIV policy and practice to date.

Improving productivity and water use efficiency: a case study of farms in England

The idea of Sustainable Intensification comes as a response to the challenge of avoiding resources such as land, water and energy being overexploited while increasing food production for an increasing demand from a growing global population. Sustainable Intensification means that farmers need to simultaneously increase yields and sustainably use limited natural resources, such as water. Within the agricultural sector water has a number of uses including irrigation, spraying, drinking for livestock and washing (vegetables, livestock buildings). In order to achieve Sustainable Intensification measures are needed that enable policy makers and managers to inform them about the relative performance of farms as well as of possible ways to improve such performance. We provide a benchmarking tool to assess water use (relative) efficiency at a farm level, suggest pathways to improve farm level productivity by identifying best practices for reducing excessive use of water for irrigation. Data Envelopment Analysis techniques including analysis of returns to scale were used to evaluate any excess in agricultural water use of 66 Horticulture Farms based on different River Basin Catchments across England. We found that farms in the sample can reduce on average water requirements by 35% to achieve the same output (Gross Margin) when compared to their peers on the frontier. In addition, 47% of the farms operate under increasing returns to scale, indicating that farms will need to develop economies of scale to achieve input cost savings. Regarding the adoption of specific water use efficiency management practices, we found that the use of a decision support tool, recycling water and the installation of trickle/drip/spray lines irrigation system has a positive impact on water use efficiency at a farm level whereas the use of other irrigation systems such as the overhead irrigation system was found to have a negative effect on water use efficiency.

Understanding digital literacies: a practical introduction

Understanding Digital Literacies provides an accessible and timely introduction to new media literacies. It supplies readers with the theoretical and analytical tools with which to explore the linguistic and social impact of a host of new digital literacy practices. Each chapter in the volume covers a different topic, presenting an overview of the major concepts, issues, problems and debates surrounding the topic, while also encouraging students to reflect on and critically evaluate their own language and communication practices. Features include: coverage of a diverse range of digital media texts, tools and practices including blogging, hypertextual organisation, Facebook, Twitter, YouTube, Wikipedia, websites and games an extensive range of examples and case studies to illustrate each topic, such as how blogs have affected our thinking about communication, how the creation and sharing of digital images and video can bring about shifts in social roles, and how the design of multiplayer online games for children can promote different ideologies a variety of discussion questions and mini-ethnographic research projects involving exploration of various patterns of media production and communication between peers, for example in the context of Wikinomics and peer production, social networking and civic participation, and digital literacies at work end of chapter suggestions for further reading and links to key web and video resources a companion website providing supplementary material for each chapter, including summaries of key issues, additional web-based exercises, and links to further resources such as useful websites, articles, videos and blogs.

Do online hotel rating schemes influence booking behaviors?

Travelers’ hotel booking behaviors increasingly depend on peers' opinions and online ratings. This study investigates the effects of online hotel ratings on travelers' attitudes toward the hotel and booking intentions, using a 2 × 2 experimental research design. The results suggest that online rating lists are more useful and credible when published by well-known online travel communities (e.g., TripAdvisor). More favorable attitudes toward a hotel and higher booking intentions emerge when the hotel appears in best hotels lists. Finally, for the entries on best hotels lists, better attitudes and higher booking intentions result if the list is published on a well-known online travel community (Tripadvisor), whereas for entries on a worst hotel list, attitudes and booking intentions decrease even further if the list appears on TripAdvisor.

Modulation of potassium channels inhibits bunyavirus infection

Bunyaviruses are considered to be emerging pathogens facilitated by the segmented nature of their genome that allows reassortment between different species to generate novel viruses with altered pathogenicity. Bunyaviruses are transmitted via a diverse range of arthropod vectors, as well as rodents, and have established a global disease range with massive importance in healthcare, animal welfare and economics. There are no vaccines or anti-viral therapies available to treat human bunyavirus infections and so development of new anti-viral strategies is urgently required. Bunyamwera virus (BUNV; genus Orthobunyavirus) is the model bunyavirus, sharing aspects of its molecular and cellular biology with all Bunyaviridae family members. Here, we show for the first time that BUNV activates and requires cellular potassium (K+) channels to infect cells. Time of addition assays using K+ channel modulating agents demonstrated that K+ channel function is critical to events shortly after virus entry but prior to viral RNA synthesis/replication. A similar K+ channel dependence was identified for other bunyaviruses namely Schmallenberg virus (Orthobunyavirus) as well as the more distantly related Hazara virus (Nairovirus). Using a rational pharmacological screening regimen, twin-pore domain K+ channels (K2P) were identified as the K+ channel family mediating BUNV K+ channel dependence. As several K2P channel modulators are currently in clinical use, our work suggests they may represent a new and safe drug class for the treatment of potentially lethal bunyavirus disease.

Rethinking the literature on the performance of Chinese multinational enterprises

We synthesize the literature on Chinese multinational enterprises (MNEs) and find that much of the prior research is based on as few as a dozen case studies of Chinese firms. They are so case-specific that it has led to a misplaced call for new theories to explain Chinese firms’ internationalization. In an attempt to better relate theory with empirical evidence, we examine the largest 500 Chinese manufacturing firms. We aim to find out the number of Chinese manufacturing firms to be true MNEs by definition, and to examine their financial performance relative to global peers using the financial benchmarking method. We develop our theoretical perspectives from new internalization theory. We find that there are only 49 Chinese manufacturing firms to be true MNEs, whereas the rest is purely domestic firms. Their performance is poor relative to global peers. Chinese MNEs have home country bound firm-specific advantages (FSAs), which are built upon home country-specific advantages (home CSAs). They have not yet developed advanced management capabilities through recombination with host CSAs. Essentially, they acquire foreign firms to increase their sales in domestic market, but they fail to be competitive internationally and to achieve superior performance in overseas operations. Our findings have important strategic implications for managers, public policy makers, and academic research.

Comparison of aerosol optical properties above clouds between POLDER and AeroCom models over the South East Atlantic Ocean during the fire season

Aerosol properties above clouds have been retrieved over the South East Atlantic Ocean during the fire season 2006 using satellite observations from POLDER (Polarization and Directionality of Earth Reflectances). From June to October, POLDER has observed a mean Above-Cloud Aerosol Optical Thickness (ACAOT) of 0.28 and a mean Above-Clouds Single Scattering Albedo (ACSSA) of 0.87 at 550 nm. These results have been used to evaluate the simulation of aerosols above clouds in 5 AeroCom (Aerosol Comparisons between Observations and Models) models (GOCART, HadGEM3, ECHAM5-HAM2, OsloCTM2 and SPRINTARS). Most models do not reproduce the observed large aerosol load episodes. The comparison highlights the importance of the injection height and the vertical transport parameterizations to simulate the large ACAOT observed by POLDER. Furthermore, POLDER ACSSA is best reproduced by models with a high imaginary part of black carbon refractive index, in accordance with recent recommendations.

Processing coordinate subject-verb agreement in L1 and L2 Greek

The present study examines the processing of subject-verb (SV) number agreement with coordinate subjects in pre-verbal and post-verbal positions in Greek. Greek is a language with morphological number marked on nominal and verbal elements. Coordinate SV agreement, however, is special in Greek as it is sensitive to the coordinate subject's position: when pre-verbal, the verb is marked for plural while when post-verbal the verb can be in the singular. We conducted two experiments, an acceptability judgment task with adult monolinguals as a pre-study (Experiment 1) and a self-paced reading task as the main study (Experiment 2) in order to obtain acceptance as well as processing data. Forty adult monolingual speakers of Greek participated in Experiment 1 and a hundred and forty one in Experiment 2. Seventy one children participated in Experiment 2: 30 Albanian-Greek sequential bilingual children and 41 Greek monolingual children aged 10–12 years. The adult data in Experiment 1 establish the difference in acceptability between singular VPs in SV and VS constructions reaffirming our hypothesis. Meanwhile, the adult data in Experiment 2 show that plural verbs accelerate processing regardless of subject position. The child online data show that sequential bilingual children have longer reading times (RTs) compared to the age-matched monolingual control group. However, both child groups follow a similar processing pattern in both pre-verbal and post-verbal constructions showing longer RTs immediately after a singular verb when the subject was pre-verbal indicating a grammaticality effect. In the post-verbal coordinate subject sentences, both child groups showed longer RTs on the first subject following the plural verb due to the temporary number mismatch between the verb and the first subject. This effect was resolved in monolingual children but was still present at the end of the sentence for bilingual children indicating difficulties to reanalyze and integrate information. Taken together, these findings demonstrate that (a) 10–12 year-old sequential bilingual children are sensitive to number agreement in SV coordinate constructions parsing sentences in the same way as monolingual children even though their vocabulary abilities are lower than that of age-matched monolingual peers and (b) bilinguals are slower in processing overall.

Long-term positive effects of repeating a year in school: Six-year longitudinal study of self-beliefs, anxiety, social relations, school grades, and test scores

Consistently with a priori predictions, school retention (repeating a year in school) had largely positive effects for a diverse range of 10 outcomes (e.g., math self-concept, self-efficacy, anxiety, relations with teachers, parents and peers, school grades, and standardized achievement test scores). The design, based on a large, representative sample of German students (N = 1,325, M age = 11.75 years) measured each year during the first five years of secondary school, was particularly strong. It featured four independent retention groups (different groups of students, each repeating one of the four first years of secondary school, total N = 103), with multiple post-test waves to evaluate short- and long-term effects, controlling for covariates (gender, age, SES, primary school grades, IQ) and one or more sets of 10 outcomes realised prior to retention. Tests of developmental invariance demonstrated that the effects of retention (controlling for covariates and pre-retention outcomes) were highly consistent across this potentially volatile early-to-middle adolescent period; largely positive effects in the first year following retention were maintained in subsequent school years following retention. Particularly considering that these results are contrary to at least some of the accepted wisdom about school retention, the findings have important implications for educational researchers, policymakers and parents.

Knowledge of basic concepts in deaf/hard of hearing children

Basic concept knowledge of children who were deaf/hard of hearing was tested using the Bracken Basic Concept Scale: 3rd Edition. These children were given both the receptive and expressive portions of the test. Results indicate delays in overall basic concept knowledge in children who are deaf compared to their normal-hearing peers.

Can physical exercise during gestation attenuate the effects of a maternal perinatal low-protein diet on oxygen consumption in rats?

A protocol of physical exercise, based on maximal oxygen uptake ((V) over dot(O2max)), for female rats before and during pregnancy was developed to evaluate the impact of a low-protein diet on oxygen consumption during gestation and growth rate of the offspring. Virgin female Wistar rats were divided into four groups as follows: untrained (NT, n = 5); trained (T, n = 5); untrained with low-protein diet (NT+LP, n = 5); and trained with low-protein diet (T+LP, n = 5). Trained rats were submitted to a protocol of moderate physical training on a treadmill over a period of 4 weeks (5 days week(-1) and 60 min day(-1), at 65% of (V) over dot(O2max)). At confirmation of pregnancy, the intensity and duration of the exercise was reduced. Low-protein groups received an 8% casein diet, and their peers received a 17% casein diet. The birthweight and growth rate of the pups up to the 90th day were recorded. Oxygen consumption ((V) over dot(O2)), CO(2) production and respiratory exchange ratio (RER) were determined using an indirect open-circuit calorimeter. Exercise training increased. (V) over dot(O2max) by about 20% when compared with the initial values (45.6 +/- 1.0 ml kg(-1) min(-1)). During gestation, all groups showed a progressive reduction in the resting (V) over dot(O2) values. Dams in the NT+LP group showed lower values of resting (V) over dot(O2) than those in the NT group. The growth rate of pups from low-protein-fed mothers was around 50% lower than that of their respective controls. The T group showed an increase in body weight from the 60th day onwards, while the NT+LP group presented a reduced body weight from weaning onwards. In conclusion, physical training attenuated the impact of the low- protein