Reversal and Re-Organization of the Northern Cities Shift in Michigan

We report initial findings from a study of the Northern Cities Shift (NCS) in Lansing, Michigan. As in other urban centers recently examined, the NCS appears to be undergoing re-evaluation and attrition. However, whereas others have found the NCS to be simply undergoing “exact reversals” of its vowel movements (Driscoll and Lape 2014), in Lansing we find two additional processes in addition to reversal: reorganization and continuation. We observe reversal of the fronting of LOT, reorganization of TRAP from a raised to a continuous or nasal system, and continuation of the lowering of DRESS. Findings are derived from a sample of 50 speakers born 1908 to 1996, combining new sociolinguistic interviews with oral histories recorded 1992–2006

Collective Aspects of Mitigating Interactions Between Large Carnivores and Humans

Understanding how to coexist with wildlife is of critical importance for successful conservation, particularly for large carnivores, who pose risks to human safety, livestock, and game species. In Montana (USA), black and grizzly bears occur across much of the western half of the state. In particular, grizzly bears are protected by the Endangered Species Act and their populations and ranges are expanding, resulting in increased overlap between humans and bears. Interactions with bears can be mitigated when landowners take certain actions to secure bear attractants – such as using bear resistant garbage cans and feed storage, using electric fences, removing livestock carcasses, and taking down bird feeders in the spring and fall. Few studies have examined what drives uptake of these actions, but factors include perceived risks and benefits and personal experience at the individual level. This research aims to understand how individual and collective aspects drive uptake of actions to secure bear attractants. We administered a mail-back questionnaire to Montana landowners and used the collective interest model to determine the relative effects of collective and individual factors in influencing whether landowners secure bear attractants. We developed logistic regression models for each behavior. Collective aspects that drove behavior included social norms (i.e., what individuals think they should do and what others are doing) and network centrality (i.e., how much social influence an individual has). This research suggests that outreach campaigns that only highlight the risks of large carnivores could be substantially improved by describing the collective aspects of mitigation

Keeping the faith: reflections on religious nurture among young British Sikhs

Although young Sikhs are regularly accused of not attending gurdwara and not being interested in Sikhism, many young Sikhs are now learning about Sikhism outside traditional religious institutions. Using data gathered as part of a research project studying the transmission of Sikhism among 18- to 30-year-old British Sikhs, this essay explores how young Sikhs are learning about Sikhism in their pre-adult life stage. Examining the influences of the family and the school environment and the various methods used in gurdwaras, this essay offers a retrospective look on the ways in which young Sikhs are nurtured and socialised into Sikhism, providing an understanding from the perspective of young Sikhs themselves about which methods actually work and why

GABA-ergic Dynamics in Human Frontotemporal Networks Confirmed by Pharmaco-Magnetoencephalography.

To bridge the gap between preclinical cellular models of disease and in vivo imaging of human cognitive network dynamics, there is a pressing need for informative biophysical models. Here we assess dynamic causal models (DCM) of cortical network responses, as generative models of magnetoencephalographic observations during an auditory oddball roving paradigm in healthy adults. This paradigm induces robust perturbations that permeate frontotemporal networks, including an evoked 'mismatch negativity' response and transiently induced oscillations. Here, we probe GABAergic influences in the networks using double-blind placebo-controlled randomized-crossover administration of the GABA reuptake inhibitor, tiagabine (oral, 10 mg) in healthy older adults. We demonstrate the facility of conductance-based neural mass mean-field models, incorporating local synaptic connectivity, to investigate laminar-specific and GABAergic mechanisms of the auditory response. The neuronal model accurately recapitulated the observed magnetoencephalographic data. Using parametric empirical Bayes for optimal model inversion across both drug sessions, we identify the effect of tiagabine on GABAergic modulation of deep pyramidal and interneuronal cell populations. We found a transition of the main GABAergic drug effects from auditory cortex in standard trials to prefrontal cortex in deviant trials. The successful integration of pharmaco- magnetoencephalography with dynamic causal models of frontotemporal networks provides a potential platform on which to evaluate the effects of disease and pharmacological interventions.SIGNIFICANCE STATEMENT Understanding human brain function and developing new treatments require good models of brain function. We tested a detailed generative model of cortical microcircuits that accurately reproduced human magnetoencephalography, to quantify network dynamics and connectivity in frontotemporal cortex. This approach identified the effect of a test drug (GABA-reuptake inhibitor, tiagabine) on neuronal function (GABA-ergic dynamics), opening the way for psychopharmacological studies in health and disease with the mechanistic precision afforded by generative models of the brain

British Sikh identity and the struggle for distinctiveness and continuity

Sikhs constitute a high proportion of the ethnic minority population in Britain. Yet, social psychologists have largely neglected this demographically important religious group, leaving much of the theorising to anthropologists and sociologists. The present study explores how a group of British‐born Sikhs understood and defined their Sikh identities, focussing upon strategies for safeguarding the continuity and distinctiveness of this identity. Ten individuals were interviewed. Informed by identity process theory, the transcripts were subjected to thematic analysis. Three superordinate themes are reported, namely (i) "Freedom and gender equality": the 'essence' of Sikh identity; (ii) Continuing the legacy of the Gurus; and (iii) Maintaining group continuity and distinctiveness in a threatening social context. Theoretical and practical implications of the research are discussed, particularly in relation to intergroup relations

GABAergic cortical network physiology in frontotemporal lobar degeneration.

The clinical syndromes caused by frontotemporal lobar degeneration are heterogeneous, including the behavioural variant frontotemporal dementia (bvFTD) and progressive supranuclear palsy. Although pathologically distinct, they share many behavioural, cognitive and physiological features, which may in part arise from common deficits of major neurotransmitters such as γ-aminobutyric acid (GABA). Here, we quantify the GABAergic impairment and its restoration with dynamic causal modelling of a double-blind placebo-controlled crossover pharmaco-magnetoencephalography study. We analysed 17 patients with bvFTD, 15 patients with progressive supranuclear palsy, and 20 healthy age- and gender-matched controls. In addition to neuropsychological assessment and structural MRI, participants undertook two magnetoencephalography sessions using a roving auditory oddball paradigm: once on placebo and once on 10 mg of the oral GABA reuptake inhibitor tiagabine. A subgroup underwent ultrahigh-field magnetic resonance spectroscopy measurement of GABA concentration, which was reduced among patients. We identified deficits in frontotemporal processing using conductance-based biophysical models of local and global neuronal networks. The clinical relevance of this physiological deficit is indicated by the correlation between top-down connectivity from frontal to temporal cortex and clinical measures of cognitive and behavioural change. A critical validation of the biophysical modelling approach was evidence from parametric empirical Bayes analysis that GABA levels in patients, measured by spectroscopy, were related to posterior estimates of patients' GABAergic synaptic connectivity. Further evidence for the role of GABA in frontotemporal lobar degeneration came from confirmation that the effects of tiagabine on local circuits depended not only on participant group, but also on individual baseline GABA levels. Specifically, the phasic inhibition of deep cortico-cortical pyramidal neurons following tiagabine, but not placebo, was a function of GABA concentration. The study provides proof-of-concept for the potential of dynamic causal modelling to elucidate mechanisms of human neurodegenerative disease, and explains the variation in response to candidate therapies among patients. The laminar- and neurotransmitter-specific features of the modelling framework, can be used to study other treatment approaches and disorders. In the context of frontotemporal lobar degeneration, we suggest that neurophysiological restoration in selected patients, by targeting neurotransmitter deficits, could be used to bridge between clinical and preclinical models of disease, and inform the personalized selection of drugs and stratification of patients for future clinical trials

Investigating the performance of a novel pH and cathepsin B sensitive, stimulus-responsive nanoparticle for optimised sonodynamic therapy in prostate cancer

Nano-formulations that are responsive to tumour-related and externally-applied stimuli can offer improved, site-specific antitumor effects, and can improve the efficacy of conventional therapeutic agents. Here, we describe the performance of a novel stimulus-responsive nanoparticulate platform for the targeted treatment of prostate cancer using sonodynamic therapy (SDT). The nanoparticles were prepared by self-assembly of poly(L-glutamic acid-L-tyrosine) co-polymer with hematoporphyrin. The nanoparticulate formulation was characterized with respect to particle size, morphology, surface charge and singlet oxygen production during ultrasound exposure. The response of the formulation to the presence of cathepsin B, a proteolytic enzyme that is overexpressed and secreted in the tumour microenvironment of many solid tumours, was assessed. Our results showed that digestion with cathepsin B led to nanoparticle size reduction. In the absence of ultrasound, the formulation exhibited greater toxicity at acidic pH than at physiological pH, using the human prostate cells lines LNCaP and PC3 as targets. Nanoparticle cellular uptake was enhanced at acidic pH – a condition that was also associated with greater cathepsin B production. Nanoparticles exhibited enhanced ultrasound-induced cytotoxicity against both prostate cancer cell lines. Subsequent proof-of-concept in vivo studies demonstrated that, when ectopic human xenograft LNCaP tumours in SCID mice were treated with SDT using the systemically-administered nanoparticulate formulation at a single dose, tumour volumes decreased by up to 64% within 24 h. No adverse effects were observed in the nanoparticle-treated mice and their body weight remained stable. The potential of this novel formulation to deliver safe and effective treatment of prostate cancer is discussed

Scleromochlus and the early evolution of Pterosauromorpha

Pterosaurs, the first vertebrates to evolve powered flight, were key components of Mesozoic terrestrial ecosystems from their sudden appearance in the Late Triassic until their demise at the end of the Cretaceous1,2,3,4,5,6. However, the origin and early evolution of pterosaurs are poorly understood owing to a substantial stratigraphic and morphological gap between these reptiles and their closest relatives6, Lagerpetidae7. Scleromochlus taylori, a tiny reptile from the early Late Triassic of Scotland discovered over a century ago, was hypothesized to be a key taxon closely related to pterosaurs8, but its poor preservation has limited previous studies and resulted in controversy over its phylogenetic position, with some even doubting its identification as an archosaur9. Here we use microcomputed tomographic scans to provide the first accurate whole-skeletal reconstruction and a revised diagnosis of Scleromochlus, revealing new anatomical details that conclusively identify it as a close pterosaur relative1 within Pterosauromorpha (the lagerpetid + pterosaur clade). Scleromochlus is anatomically more similar to lagerpetids than to pterosaurs and retains numerous features that were probably present in very early diverging members of Avemetatarsalia (bird-line archosaurs). These results support the hypothesis that the first flying reptiles evolved from tiny, probably facultatively bipedal, cursorial ancestors1