Although peer review has been shown to be beneficial in many writing classrooms, the benefits of peer review to the reviewer, or the student giving feedback, has not been thoroughly investigated in ...second-language writing research. The purpose of this study is to determine which is more beneficial to improving student writing: giving or receiving peer feedback. The study was conducted at an intensive English institute with ninety-one students in nine writing classes at two proficiency levels. The “givers” reviewed anonymous papers but received no peer feedback over the course of the semester, while the “receivers” received feedback but did not review other students’ writing. An analysis in the gains in writing ability measured from writing samples collected at the beginning and end of the semester indicated that the givers, who focused solely on reviewing peers’ writing, made more significant gains in their own writing over the course of the semester than did the receivers, who focused solely on how to use peer feedback. Results also indicated that givers at the lower proficiency level made more gains than those at higher proficiency levels and that slightly more gains were observed on global than local aspects of writing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Despite the established dogma of central nervous system (CNS) immune privilege, neuroimmune interactions play an active role in diverse neurological disorders. However, the precise mechanisms ...underlying CNS immune surveillance remain elusive; particularly, the anatomical sites where peripheral adaptive immunity can sample CNS-derived antigens and the cellular and molecular mediators orchestrating this surveillance. Here, we demonstrate that CNS-derived antigens in the cerebrospinal fluid (CSF) accumulate around the dural sinuses, are captured by local antigen-presenting cells, and are presented to patrolling T cells. This surveillance is enabled by endothelial and mural cells forming the sinus stromal niche. T cell recognition of CSF-derived antigens at this site promoted tissue resident phenotypes and effector functions within the dural meninges. These findings highlight the critical role of dural sinuses as a neuroimmune interface, where brain antigens are surveyed under steady-state conditions, and shed light on age-related dysfunction and neuroinflammatory attack in animal models of multiple sclerosis.
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•CNS-derived antigens accumulate at dural sinuses and are captured by dural APCs•Dural sinus-associated APCs present CSF-borne antigens to patrolling T cells•The dural sinus stroma orchestrates T cell trafficking•Immune hubs along dural sinuses allow CNS immunosurveillance
Rustenhoven et al. identify the dural sinuses as a neuroimmune interface, where patrolling T cells survey brain- and CSF-derived antigens to enable CNS immune surveillance. This niche is altered during aging and neuroinflammation and may represent a new therapeutic target for neurological diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cobalt-porphyrin phospholipid displays recombinant protein antigens on liposome surfaces via antigen polyhistidine-tag (His-tag), and when combined with monophosphorylated lipid A and QS-21 yields ...the “CPQ” vaccine adjuvant system. In this proof of principle study, CPQ was used to generate vaccine prototypes that elicited antibodies for two different alphaviruses (AV). Mice were immunized with computationally designed, His-tagged, physicochemical property consensus (PCPcon) protein antigens representing the variable B-domain of the envelope protein 2 (E2) from the serotype specific Venezuelan Equine Encephalitis Virus (VEEVcon) or a broad-spectrum AV-antigen termed EVCcon. The CPQ adjuvant enhanced the antigenicity of both proteins without eliciting detectable anti-His-tag antibodies. Antibodies elicited from mice immunized with antigens admixed with CPQ showed orders-of-magnitude higher levels of antigen-specific IgG compared to alternative control adjuvants. The ELISA results correlated with antiviral activity against VEEV strain TC83 and more weakly to Chikungunya virus 118/25. Thus, display of E.coli-produced His-tagged E2 protein segments on the surface of immunogenic liposomes elicits high levels of antigen-specific and AV neutralizing antibodies in mice with vaccination, while facilitating vaccine preparation and providing dose-sparing potential.
•His-tagged alphavirus physicochemical consensus (PCP) antigens bind to CoPoP liposomes.•PCP alphavirus antigens better induce antibodies when displayed on liposomes.•Alphavirus neutralizing antibodies are induced with broad reactivity to alphavirus antigens.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There is a pressing need for new vaccines against alphaviruses, which can cause fatal encephalitis (Venezuelan equine encephalitis virus (VEEV) and others) and severe arthralgia (e.g. Chikungunya ...virus, CHIKV). These positive-strand RNA viruses are diverse and evolve rapidly, meaning that the sequence of any vaccine should cover multiple strains that may be quite different from any previous isolate. Here, consensus proteins were produced to represent the common physicochemical properties (PCPs) of the epitope rich, B domain of the E2 envelope protein. PCP-consensus proteins were based on multiple strains of VEEV (VEEVcon) and CHIKV (CHIKVcon) or the conserved PCPs of 24 different alphaviruses (AllAVcon). The AllAVcon was altered to include binding sites for neutralizing antibodies of both VEEV and CHIKV strains (Mosaikcon). All four designed proteins were produced solubly in E. coli and purified. They formed the β-strand core expected from experimental structures of this region of the wild type E2 proteins as indicated by circular dichroism (CD) spectra. Furthermore, the CHIKVcon protein bound to a structure dependent, CHIKV neutralizing monoclonal antibody. The AllAVcon and Mosaikcon proteins bound to polyclonal antibodies generated during natural infection with either VEEV or CHIKV, indicating they contained epitopes of both serotypes. The Mosaikcon antigen induced antibodies in rabbit sera that recognized both the VEEVcon and CHIKVcon spike proteins. These PCP-consensus antigens are promising starting points for novel, broad-spectrum alphavirus vaccines.
•Design of PCP-consensus & mosaic alphavirus spike domains.•Purified recombinant PCP-consensus proteins fold correctly.•Antigens project epitopes of both VEEV and CHIKV, which are 65% diverse.•Proteins could be the basis for a broad spectrum alphavirus vaccine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Second language (L2) gains during study abroad have been related to several variables including length of stay (Llanes, 2011), language use (Martinsen, Baker, Dewey, Bown, & Johnson, 2010), and ...social network development (Isabelli‐García, 2006), among others. However, most studies have investigated only a few predictors in single study abroad programs. While these findings are helpful, larger scale studies are needed to better understand the variables that contribute to L2 gains across several different cultures and learner groups. The current study examines predictors of L2 gain of more than 100 native English speakers who participated in study abroad in Mexico, Spain, France, Egypt, Russia, and China. Participants were asked to complete an ACTFL Oral Proficiency Interview at the beginning and end of their study abroad program. Participants were then divided into “gainers” and “non‐gainers,” or those who did or did not make significant language gains from pre‐ to posttest. Their language gains from pre to posttest were compared to several predictors: personality (measured by the NEO Five‐Factor Inventory), social networks (size, dispersion, density, etc.), intercultural sensitivity (measured by the Intercultural Development Inventory), amount of second language use, gender, and age. Results suggest that many students were able to make gains in language, in each of the programs, and that the strongest predictors of L2 gains were cultural sensitivity and social network variables.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Mutations in MECP2, encoding the epigenetic regulator methyl-CpG-binding protein 2, are the predominant cause of Rett syndrome, a disease characterized by both neurological symptoms and systemic ...abnormalities. Microglial dysfunction is thought to contribute to disease pathogenesis, and here we found microglia become activated and subsequently lost with disease progression in Mecp2-null mice. Mecp2 was found to be expressed in peripheral macrophage and monocyte populations, several of which also became depleted in Mecp2-null mice. RNA-seq revealed increased expression of glucocorticoid- and hypoxia-induced transcripts in Mecp2-deficient microglia and peritoneal macrophages. Furthermore, Mecp2 was found to regulate inflammatory gene transcription in response to TNF stimulation. Postnatal re-expression of Mecp2 using Cx3cr1creER increased the lifespan of otherwise Mecp2-null mice. These data suggest that Mecp2 regulates microglia and macrophage responsiveness to environmental stimuli to promote homeostasis. Dysfunction of tissue-resident macrophages might contribute to the systemic pathologies observed in Rett syndrome.
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•Mecp2 is broadly expressed in macrophages and resident monocytes•Mecp2-null mice exhibit monocyte and resident macrophage deficiencies•Mecp2 expression under Cx3cr1creER extends survival of Mecp2Lox-Stop/y mice•Mecp2 regulates transcriptional responses to inflammatory stimuli
Mutations in the gene encoding Methyl-CpG binding protein 2 (MeCP2) are the primary cause of the neurodevelopmental disease Rett syndrome. Kipnis and colleagues demonstrate that Mecp2 regulates macrophage transcriptional responses to glucocorticoid and inflammatory stimuli, raising the possibility that abnormal macrophage responses contribute to systemic impairments in Rett syndrome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study explores native English speakers’ (NESs) self‐reported comfort levels when speaking with non‐native English speakers (NNESs) from different first language (L1) backgrounds and in six ...different communication situations. NESs (n = 122) listened to Spanish L1 and Chinese L1 NNESs with low, mid or high levels of English proficiency and rated their comfort level interacting with them. Results indicated that higher proficiency speakers were rated significantly higher (more comfortable as interlocutors) than Mid which were in turn rated higher than Low proficiency speakers. Spanish L1 speakers were rated higher than Chinese L1 speakers except at low proficiency levels. Ratings for more casual communication situations were higher than more formal situations. Results suggest that communicative expectations may be different for Spanish and Chinese speakers.
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Este estudio explora los niveles de confort reportados por angloparlantes nativos (AN) al hablar con angloparlantes no nativos (ANN) cuyo primer idioma (L1) es distinto al inglés. Esta información fue auto reportada por los participantes en base a seis diferentes situaciones comunicativas. Los ANs interactuaron con ANNs cuyo L1 era español y con ANNs cuyo L1 era chino. Ambos grupos de ANNs tenían niveles bajos, medios, o altos de dominio de inglés y calificaron su nivel de confort a medida que interactuaban con los AN. Los resultados indicaron que los ANNs con dominio más alto obtuvieron las calificaciones más altas, indicando que eran los interlocutores que interactuaban con mayor comodidad. A cambio, los hablantes con dominio medio de inglés obtuvieron la calificación media, y los hablantes con dominio de inglés bajo obtuvieron las calificaciones más bajas. Los ANNs cuyo L1 era español calificaron más alto que los ANNs cuyo L1 era chino, con excepción al nivel bajo de inglés. Las calificaciones para situaciones comunicativas más casuales fueron más altas que en situaciones más formales. Los resultados sugieren que las expectativas de comunicación pueden ser diferentes para hablantes de español y para hablantes de chino.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Inflammatory processes arising from metabolic abnormalities are known to precipitate the development of CVD. ...Several metabolic and inflammatory markers have been proposed for predicting the progression of CVD, including high density lipoprotein cholesterol (HDL‐C). For ~50 years, HDL‐C has been considered as the atheroprotective ‘good’ cholesterol because of its strong inverse association with the progression of CVD. Thus, interventions to increase the concentration of HDL‐C have been successfully tested in animals; however, clinical trials were unable to confirm the cardiovascular benefits of pharmaceutical interventions aimed at increasing HDL‐C levels. Based on these data, the significance of HDL‐C in the prevention of CVD has been called into question. Fundamental in vitro and animal studies suggest that HDL‐C functionality, rather than HDL‐C concentration, is important for the CVD‐preventive qualities of HDL‐C. Our current review of the literature positively demonstrates the negative impact of systemic and tissue (i.e. adipose tissue) inflammation in the healthy metabolism and function of HDL‐C. Our survey indicates that HDL‐C may be a good marker of adipose tissue health, independently of its atheroprotective associations. We summarize the current findings on the use of anti‐inflammatory drugs to either prevent HDL‐C clearance or improve the function and production of HDL‐C particles. It is evident that the therapeutic agents currently available may not provide the optimal strategy for altering HDL‐C metabolism and function, and thus, further research is required to supplement this mechanistic approach for preventing the progression of CVD.
Linked Articles
This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Vaccines based on proteins and peptides may be safer and if calculated based on many sequences, more broad-spectrum than those designed based on single strains. Physicochemical Property Consensus ...(PCPcon) alphavirus (AV) antigens from the B-domain of the E2 envelope protein were designed, synthesized recombinantly and shown to be immunogenic (i.e. sera after inoculation detected the antigen in dotspots and ELISA). Antibodies in sera after inoculation with B-region antigens based on individual AV species (eastern or Venezuelan equine encephalitis (EEEVcon, VEEVcon), or chikungunya (CHIKVcon) bound only their cognate protein, while those designed against multiple species (Mosaikcon and EVCcon) recognized all three serotype specific antigens. The VEEVcon and EEEVcon sera only showed antiviral activity against their related strains (in plaque reduction neutralization assays (PRNT50/80). Peptides designed to surface exposed areas of the E2-A-domain of CHIKVcon were added to CHIKVcon inocula to provide anti-CHIKV antibodies. EVCcon, based on three different alphavirus species, combined with E2-A-domain peptides from AllAVcon, a PCPcon of 24 diverse AV, generated broad spectrum, antiviral antibodies against VEEV, EEEV and CHIKV, AV with less than 35% amino acid identity to each other (>65% diversity). This is a promising start to a molecularly defined vaccine against all AV. Further study with these antigens can illuminate what areas are most important for a robust immune response, resistant to mutations in rapidly evolving viruses. The validated computational methods can also be used to design broad spectrum antigens against many other pathogen families.
•PCP consensus antigens VEEVcon, EEEVcon and CHIKVcon generate species specific antibodies.•A completely computational protein, EVCcon, generates broad spectrum antibodies.•EVCcon inoculation yields antiviral antibodies against 3 diverse AV species in PRNT.•Surface exposed E2-A region peptides are needed to protect against Chikungunya virus.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study examined whether learning context (ESL versus EFL) and language learning aptitude (high versus low) affected the use of second-language pronunciation strategies and pronunciation ...achievement. The top and lowest scorers (n = 60) on the Pimsleur Language Learning Aptitude Battery (PLAB) Test were asked to complete a pronunciation strategies inventory and participate in pronunciation proficiency tests at the beginning and end of a 10-week speaking class. Pronunciation scores in global foreign accent, fluency, comprehensibility, and accuracy were compared with both overall and individual section PLAB scores and pronunciation strategies use. Results indicated that neither types of learning strategies nor degree of language gains differed over EFL and ESL contexts. However, participants' post-test pronunciation scores in global foreign accent, fluency, and accuracy were positively correlated with auditory aptitude and motivation, while comprehensibility post-test scores were correlated with pronunciation strategies use. The findings for this study suggest that learning context plays a limited role in strategy use and that aptitude affects pronunciation accuracy and pronunciation strategies affect comprehensibility. Thus, strategy and aptitude affect different aspects of pronunciation. Adapted from the source document
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