MEG Evidence for Incremental Sentence Composition in the Anterior Temporal Lobe

Research investigating the brain basis of language comprehension has associated the left anterior temporal lobe (ATL) with sentence‐level combinatorics. Using magnetoencephalography (MEG), we test the parsing strategy implemented in this brain region. The number of incremental parse steps from a predictive left‐corner parsing strategy that is supported by psycholinguistic research is compared with those from a less‐predictive strategy. We test for a correlation between parse steps and source‐localized MEG activity recorded while participants read a story. Left‐corner parse steps correlated with activity in the left ATL around 350–500 ms after word onset. No other correlations specific to sentence comprehension were observed. These data indicate that the left ATL engages in combinatoric processing that is well characterized by a predictive left‐corner parsing strategy.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137231/1/cogs12445-sup-0001-AppendixS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137231/2/cogs12445.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137231/3/cogs12445_am.pd

Shared neural correlates for building phrases in signed and spoken language

Abstract Research on the mental representation of human language has convincingly shown that sign languages are structured similarly to spoken languages. However, whether the same neurobiology underlies the online construction of complex linguistic structures in sign and speech remains unknown. To investigate this question with maximally controlled stimuli, we studied the production of minimal two-word phrases in sign and speech. Signers and speakers viewed the same pictures during magnetoencephalography recording and named them with semantically identical expressions. For both signers and speakers, phrase building engaged left anterior temporal and ventromedial cortices with similar timing, despite different linguistic articulators. Thus the neurobiological similarity of sign and speech goes beyond gross measures such as lateralization: the same fronto-temporal network achieves the planning of structured linguistic expressions

Assisted evolution enables HIV-1 to overcome a high trim5α-imposed genetic barrier to rhesus macaque tropism

Diversification of antiretroviral factors during host evolution has erected formidable barriers to cross-species retrovirus transmission. This phenomenon likely protects humans from infection by many modern retroviruses, but it has also impaired the development of primate models of HIV-1 infection. Indeed, rhesus macaques are resistant to HIV-1, in part due to restriction imposed by the TRIM5α protein (rhTRIM5α). Initially, we attempted to derive rhTRIM5α-resistant HIV-1 strains using two strategies. First, HIV-1 was passaged in engineered human cells expressing rhTRIM5α. Second, a library of randomly mutagenized capsid protein (CA) sequences was screened for mutations that reduced rhTRIM5α sensitivity. Both approaches identified several individual mutations in CA that reduced rhTRIM5α sensitivity. However, neither approach yielded mutants that were fully resistant, perhaps because the locations of the mutations suggested that TRIM5α recognizes multiple determinants on the capsid surface. Moreover, even though additive effects of various CA mutations on HIV-1 resistance to rhTRIM5α were observed, combinations that gave full resistance were highly detrimental to fitness. Therefore, we employed an 'assisted evolution' approach in which individual CA mutations that reduced rhTRIM5α sensitivity without fitness penalties were randomly assorted in a library of viral clones containing synthetic CA sequences. Subsequent passage of the viral library in rhTRIM5α-expressing cells resulted in the selection of individual viral species that were fully fit and resistant to rhTRIM5α. These viruses encoded combinations of five mutations in CA that conferred complete or near complete resistance to the disruptive effects of rhTRIM5α on incoming viral cores, by abolishing recognition of the viral capsid. Importantly, HIV-1 variants encoding these CA substitutions and SIVmac239 Vif replicated efficiently in primary rhesus macaque lymphocytes. These findings demonstrate that rhTRIM5α is difficult to but not impossible to evade, and doing so should facilitate the development of primate models of HIV-1 infection

Exogenous expression of a dominant negative RORa1 vector in muscle cells impairs differentiation: RORa1 directly interacts with p300 and MyoD

ROR/RZR is an orphan nuclear receptor that has no known ligand in the 'classical sense'. In the present study we demonstrate that RORalpha is constitutively expressed during the differentiation of proliferating myoblasts to post-mitotic multinucleated myotubes, that have acquired a contractile phenotype. Exogenous expression of dominant negative RORalpha1DeltaE mRNA in myogenic cells significantly reduces the endogenous expression of RORalpha1 mRNA, represses the accumu-lation and delays the activation of mRNAs encoding MyoD and myogenin [the muscle-specific basic helix-loop-helix (bHLH) proteins] and p21(Waf- 1/Cip-1) (a cdk inhibitor). Immunohistochemistry demonstrates that morpho-logical differentiation is delayed in cells expressing the RORDeltaE transcript. Furthermore, the size and development of mutlinucleated myotubes is impaired. The E region of RORalpha1 interacts with p300, a cofactor that functions as a coactivator in nuclear receptor and MyoD-mediated transactivation. Consistent with the functional role of RORalpha1 in myogenesis, we observed that RORalpha1 directly interacts with the bHLH protein MyoD. This interaction was mediated by the N-terminal activation domain of the bHLH protein, MyoD, and the RORalpha1 DNA binding domain/C region. Furthermore, we demonstrated that p300, RORalpha1 and MyoD interact in a non- competitive manner. In conclusion, this study provides evidence for a biological role and positive influence of RORalpha1 in the cascade of events involved in the activation of myogenic-specific markers and cell cycle regulators and suggests that crosstalk between theretinoid- relatedorphan (ROR) nuclear receptors and the myogenic bHLH proteins has functional consequences for differentiation

International medical graduates in family medicine in the United States of America: an exploration of professional characteristics and attitudes

BACKGROUND: The number of international medical graduates (IMGs) entering family medicine in the United States of America has steadily increased since 1997. Previous research has examined practice locations of these IMGs and their role in providing care to underserved populations. To our knowledge, research does not exist comparing professional profiles, credentials and attitudes among IMG and United States medical graduate (USMG) family physicians in the United States. The objective of this study is to determine, at the time when a large influx of IMGs into family medicine began, whether differences existed between USMG and IMG family physicians in regard to personal and professional characteristics and attitudes that may have implications for the health care system resulting from the increasing numbers of IMGs in family medicine in the United States. METHODS: This is a secondary data analysis of the 1996–1997 Community Tracking Study (CTS) Physician Survey comparing 2360 United States medical graduates and 366 international medical graduates who were nonfederal allopathic or osteopathic family physicians providing direct patient care for at least 20 hours per week. RESULTS: Compared to USMGs, IMGs were older (p < 0.001) and practised in smaller (p = 0.0072) and younger practices (p < 0.001). Significantly more IMGs practised in metropolitan areas versus rural areas (p = 0.0454). More IMG practices were open to all new Medicaid (p = 0.018) and Medicare (p = 0.0451) patients, and a greater percentage of their revenue was derived from these patients (p = 0.0020 and p = 0.0310). Fewer IMGs were board-certified (p < 0.001). More IMGs were dissatisfied with their overall careers (p = 0.0190). IMGs and USMGs did not differ in terms of self-rated ability to deliver high-quality care to their patients (p = 0.4626). For several of the clinical vignettes, IMGs were more likely to order tests, refer patients to specialists or require office visits than USMGs. CONCLUSION: There are significant differences between IMG and USMG family physicians' professional profiles and attitudes. These differences from 1997 merit further exploration and possible follow-up, given the increased proportion of family physicians who are IMGs in the United States

What’s missing from legal geography and materialist studies of law? Absence and the assembling of asylum appeal hearings in Europe

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: Due to the ethical and legally sensitive nature of the research, ethnographic notes taken in court could not be made openly available. Appellant interviewees were not asked for their permission to share their interview transcripts in an online open archive because of concerns that they could misunderstand what was being asked for, or feel obliged to agree but subsequently feel less able to conduct free conversation in research interviews as a result, thereby negatively impacting on the quality of the data generated. Additional details relating to, and data resulting from, to a survey taken during observations of British asylum appeals between 2013 and 2016 are available from the UK Data Archive (persistent identifier: 10.5255/UKDA-SN-852032).There is an absence of absence in legal geography and materialist studies of the law. Drawing on a multi‐sited ethnography of European asylum appeal hearings, this paper illustrates the importance of absences for a fully‐fledged materiality of legal events. We show how absent materials impact hearings, that non‐attending participants profoundly influence them, and that even when participants are physically present, they are often simultaneously absent in other, psychological registers. In so doing we demonstrate the importance and productivity of thinking not only about law's omnipresence but also the absences that shape the way law is experienced and practiced. We show that attending to the distribution of absence and presence at legal hearings is a way to critically engage with legal performance.Economic and Social Research Council (ESRC)European Research Council (ERC

Comparison of rhenium–porphyrin dyads for CO₂ photoreduction: photocatalytic studies and charge separation dynamics studied by time-resolved IR spectroscopy

We report a study of the photocatalytic reduction of CO₂ to CO by zinc porphyrins covalently linked to [ReI(2,2′-bipyridine)(CO)₃L]⁺/⁰ moieties with visible light of wavelength >520 nm. Dyad 1 contains an amide C₆H₄NHC(O) link from porphyrin to bipyridine (Bpy), Dyad 2 contains an additional methoxybenzamide within the bridge C₆H₄NHC(O)C₆H₃(OMe)NHC(O), while Dyad 3 has a saturated bridge C₆H₄NHC(O)CH₂; each dyad is studied with either L = Br or 3-picoline. The syntheses, spectroscopic characterisation and cyclic voltammetry of Dyad 3 Br and [Dyad 3 pic]OTf are described. The photocatalytic performance of [Dyad 3 pic]OTf in DMF/triethanolamine (5 : 1) is approximately an order of magnitude better than [Dyad 1 pic]PF₆ or [Dyad 2 pic]OTf in turnover frequency and turnover number, reaching a turnover number of 360. The performance of the dyads with Re–Br units is very similar to that of the dyads with [Re–pic]⁺ units in spite of the adverse free energy of electron transfer. The dyads undergo reactions during photocatalysis: hydrogenation of the porphyrin to form chlorin and isobacteriochlorin units is detected by visible absorption spectroscopy, while IR spectroscopy reveals replacement of the axial ligand by a triethanolaminato group and insertion of CO₂into the latter to form a carbonate. Time-resolved IR spectra of [Dyad 2 pic]OTf and [Dyad 3 pic]OTf (560 nm excitation in CH₂Cl₂) demonstrated electron transfer from porphyrin to Re(Bpy) units resulting in a shift of ν(CO) bands to low wavenumbers. The rise time of the charge-separated species for [Dyad 3 pic]OTf is longest at 8 (±1) ps and its lifetime is also the longest at 320 (±15) ps. The TRIR spectra of Dyad 1 Br and Dyad 2 Br are quite different showing a mixture of 3MLCT, IL and charge-separated excited states. In the case of Dyad 3 Br, the charge-separated state is absent altogether. The TRIR spectra emphasize the very different excited states of the bromide complexes and the picoline complexes. Thus, the similarity of the photocatalytic data for bromide and picoline dyads suggests that they share common intermediates. Most likely, these involve hydrogenation of the porphyrin and substitution of the axial ligand at rhenium

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Disentangling canid howls across multiple species and subspecies: Structure in a complex communication channel.

Wolves, coyotes, and other canids are members of a diverse genus of top predators of considerable conservation and management interest. Canid howls are long-range communication signals, used both for territorial defence and group cohesion. Previous studies have shown that howls can encode individual and group identity. However, no comprehensive study has investigated the nature of variation in canid howls across the wide range of species. We analysed a database of over 2000 howls recorded from 13 different canid species and subspecies. We applied a quantitative similarity measure to compare the modulation pattern in howls from different populations, and then applied an unsupervised clustering algorithm to group the howls into natural units of distinct howl types. We found that different species and subspecies showed markedly different use of howl types, indicating that howl modulation is not arbitrary, but can be used to distinguish one population from another. We give an example of the conservation importance of these findings by comparing the howls of the critically endangered red wolves to those of sympatric coyotes Canis latrans, with whom red wolves may hybridise, potentially compromising reintroduced red wolf populations. We believe that quantitative cross-species comparisons such as these can provide important understanding of the nature and use of communication in socially cooperative species, as well as support conservation and management of wolf populations.Recording work was approved by the Institutional Animal Care and Use Committee of the University of Tennessee. AK is supported by a Herchel Smith postdoctoral fellowship at the University of Cambridge. Part of this work was carried out while AK was a Postdoctoral Fellow at the National Institute for Mathematical and Biological Synthesis, an Institute sponsored by the National Science Foundation through NSF Award #DBI-1300426, with additional support from The University of Tennessee, Knoxville. BH is thankful to the State Forest Departments of Himachal Pradesh, J&K, and Maharashtra, and to various zoos in India for permitting us to record howls. HRG is grateful to all who helped with the project: the staff at Colchester Zoo; the Wildwood Trust, the Borror Laboratory of Bioacoustics; the British Library; Lupus Laetus; Polish Mammal Research Institute; Tigress Productions; the BBC Natural History Unit; Longleat Safari Park; Tierstimmen Archiv; Wild Sweden; Wolf Park; the Macaulay Sound Library and the UK Wolf Conservation Trust; and Mike Collins, Teresa Palmer, Monty Sloan, Karl-Heinz Frommolt, Yorgos Iliopoulos, Christine Anhalt, Louise Gentle, Richard Yarnell, Victoria Allison Hughes and Susan Parks. BRM thanks the USDA/APHIS/WS/National Wildlife Research Center for supporting his doctoral research and providing access to captive coyotes; recording work was approved by the NWRC IACUC. SW thanks Mariana Olsen for assistance with data collection, and Yellowstone National Park for permission to record.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.beproc.2016.01.00