Calcium-Dependent But Action Potential-Independent BCM-Like Metaplasticity in the Hippocampus

The Bienenstock, Cooper and Munro (BCM) computational model, which incorporates a metaplastic sliding threshold for LTP induction, accounts well for experience-dependent changes in synaptic plasticity in the visual cortex. BCM-like metaplasticity over a shorter timescale has also been observed in the hippocampus, thus providing a tractable experimental preparation for testing specific predictions of the model. Here, using extracellular and intracellular electrophysiological recordings from acute rat hippocampal slices, we tested the critical BCM predictions (1) that high levels of synaptic activation will induce a metaplastic state that spreads across dendritic compartments, and (2) that postsynaptic cell-firing is the critical trigger for inducing that state. In support of the first premise, high-frequency priming stimulation inhibited subsequent long-term potentiation and facilitated subsequent long-term depression at synapses quiescent during priming, including those located in a dendritic compartment different to that of the primed pathway. These effects were not dependent on changes in synaptic inhibition or NMDA/ metabotropic glutamate receptor function. However, in contrast to the BCM prediction, somatic action potentials during priming were neither necessary nor sufficient to induce the metaplasticity effect. Instead, in broad agreement with derivatives of the BCM model, calcium as released from intracellular stores and triggered byM1 muscarinic acetylcholine receptor activation was critical for altering subsequent synapticplasticity. These results indicate that synaptic plasticity in stratum radiatum of CA1 can be homeostatically regulated by the cell-wide history of synaptic activity through a calcium-dependent but action potential-independent mechanis

Public health and climate change: How are local authorities preparing for the health impacts of our changing climate?

BACKGROUND: Local authorities have a crucial role in preparing for the impacts of climate change. However, the extent to which health impacts are being prioritized and acted on is not well understood. METHODS: We investigated the role of public health in adapting to climate change through: (i) a content analysis of local authority climate change adaptation strategies in South West England and (ii) semi-structured telephone interviews with local authority public health consultants and sustainability officers and a regional Public Health England representative (n = 11). RESULTS: Adaptation strategies/plans varied in existence and scope. Public health consultants did not have an explicit remit for climate change adaptation, although related action often aligned with public health's emergency planning functions. Key barriers to health-related adaptation were financial constraints, lack of leadership and limited public and professional awareness about health impacts. CONCLUSIONS: Local authorities in South West England have differing approaches to tackling health impacts of climate change, and the prominence of public health arguments for adaptation varies. Improved public health intelligence, concise communications, targeted support, visible local and national leadership and clarity on economic costs and benefits of adaptation would be useful for local authorities in preparing for the health impacts of climate change

Amici Curiae Brief of the International Municipal Lawyers Association and Legal Scholars in Support of Defendants-Appellees in Portland Pipe Line Corporation, et al. v. City of South Portland, et al.

This brief to the Maine Supreme Judicial Court was filed in support of the City of South Portland by the Amici Curiae, including the International Municipal Lawyers Association and legal scholars, to provide the Court with a background on the role of local governments in land use planning, and to explain why the City of South Portland’s Clear Skies Ordinance falls easily within the City’s authority and was not preempted by state legislation.After studying the potential for bulk loading of crude oil within its boundaries, the City of South Portland concluded that the infrastructure requirements and environmental impacts of the activity posed a threat to public health and welfare and were incompatible with the community’s vision of itself for the future. The City therefore decided to enact the Clear Skies Ordinance, which prohibits the storing and handling of petroleum or petroleum products for the bulk loading of crude oil onto any marine tank vessel in specified zoning districts. Litigation followed, with plaintiffs arguing that the City lacked authority to enact the Ordinance and that, even if it had such authority in the first instance, that authority had been preempted by other state law. Defendants prevailed on summary judgment in the U.S. District Court for the District of Maine, and during the course of an appeal to the United States Court of Appeals for the First Circuit, the Circuit certified several questions to the Maine Supreme Judicial Court. This brief was filed in support of the City with regard to those certified questions.The brief begins by discussing how central the role of local governments is in making land use decisions, emphasizing the highly localized impacts of land use decisions for public health and welfare. It then describes the zoning mechanisms by which local governments exercise their land use power, and discusses why the zoning power is so important for protecting public health and environmental quality, and responding to the changing needs of communities.Next, the brief explains the legal underpinnings of the City of South Portland’s home rule authority. The Constitution of the State of Maine contains a broad grant of home rule authority that is further strengthened by a statutorily imposed rebuttable presumption of validity for exercises of that authority. Local exercises of zoning authority are consistent within this home rule grant, and the brief discusses why the Clear Skies Ordinance falls squarely within the local zoning power. Finally, the brief explains why the Ordinance has not been expressly or impliedly preempted by state law. For all of those reasons, the brief concludes that the City’s enactment of the Ordinance was valid in the first instance and should not be overturned

A Mendelian randomization study of the causal association between anxiety phenotypes and schizophrenia

Schizophrenia shows a genetic correlation with both anxiety disorder and neuroticism, a trait strongly associated with anxiety. However, genetic correlations do not discern causality from genetic confounding. We therefore aimed to investigate whether anxiety-related phenotypes lie on the causal pathway to schizophrenia using Mendelian randomization (MR). Four MR methods, each with different assumptions regarding instrument validity, were used to investigate casual associations of anxiety and neuroticism related phenotypes on schizophrenia, and vice versa: inverse variance weighted (IVW), weighted median, weighted mode, and, when appropriate, MR Egger regression. MR provided evidence of a causal effect of neuroticism on schizophrenia (IVW odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.12-1.59), but only weak evidence of a causal effect of anxiety on schizophrenia (IVW OR: 1.10, 95% CI: 1.01-1.19). There was also evidence of a causal association from schizophrenia liability to anxiety disorder (IVW OR: 1.28, 95% CI: 1.18-1.39) and worry (IVW beta: 0.05, 95% CI: 0.03-0.07), but effect estimates from schizophrenia to neuroticism were inconsistent in the main analysis. The evidence of neuroticism increasing schizophrenia risk provided by our results supports future efforts to evaluate neuroticism- or anxiety-based therapies to prevent onset of psychotic disorders

Disentangling controls on animal abundance: Prey availability, thermal habitat, and microhabitat structure

The question of what controls animal abundance has always been fundamental to ecology, but given rapid environmental change, understanding the drivers and mechanisms governing abundance is more important than ever. Here, we determine how multidimensional environments and niches interact to determine population abundance along a tropical habitat gradient. Focusing on the endemic lizard Anolis bicaorum on the island of Utila (Honduras), we evaluate direct and indirect effects of three interacting niche axes on abundance: thermal habitat quality, structural habitat quality, and prey availability. We measured A. bicaorum abundance across a series of thirteen plots and used N-mixture models and path analysis to disentangle direct and indirect effects of these factors. Results showed that thermal habitat quality and prey biomass both had positive direct effects on anole abundance. However, thermal habitat quality also influenced prey biomass, leading to a strong indirect effect on abundance. Thermal habitat quality was primarily a function of canopy density, measured as leaf area index (LAI). Despite having little direct effect on abundance, LAI had a strong overall effect mediated by thermal quality and prey biomass. Our results demonstrate the role of multidimensional environments and niche interactions in determining animal abundance and highlight the need to consider interactions between thermal niches and trophic interactions to understand variation in abundance, rather than focusing solely on changes in the physical environment

Visuospatial Processing Deficits Linked to Posterior Brain Regions in Premanifest and Early Stage Huntington's Disease.

OBJECTIVES: Visuospatial processing deficits have been reported in Huntington's disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. METHODS: We compared 119 premanifest (55> and 64<10.8 years to expected disease onset) and 104 early symptomatic (59 stage-1 and 45 stage-2) gene carriers, with 110 controls on visual search and mental rotation performance at baseline and 12 months. In the disease groups, we also examined associations between task performance and disease severity, functional capacity and structural brain measures. RESULTS: Cross-sectionally, there were strong differences between all disease groups and controls on visual search, and between diagnosed groups and controls on mental rotation accuracy. Only the premanifest participants close to onset took longer than controls to respond correctly to mental rotation. Visual search negatively correlated with disease burden and motor symptoms in diagnosed individuals, and positively correlated with functional capacity. Mental rotation ("same") was negatively correlated with motor symptoms in stage-2 individuals, and positively correlated with functional capacity. Visual search and mental rotation were associated with parieto-occipital (pre-/cuneus, calcarine, lingual) and temporal (posterior fusiform) volume and cortical thickness. Longitudinally, visual search deteriorated over 12 months in stage-2 individuals, with no evidence of declines in mental rotation. CONCLUSIONS: Our findings provide evidence linking early visuospatial deficits to functioning and posterior cortical dysfunction in HD. The findings are important since large research efforts have focused on fronto-striatal mediated cognitive changes, with little attention given to aspects of cognition outside of these areas. (JINS, 2016, 22, 595-608)

Labour market experiences of young UK Bangladeshi men: Identity, inclusion and exclusion in inner-city London

Detailed qualitative data are used to explore the processes perpetuatinglabour market disadvantage among young UK-Bangladeshi men living in central London. Strong forces of inclusion within the Bangladeshi community are found to interact with forces of exclusion from ‘mainstream’ society to constrain aspirations and limit opportunities. Though diverse forms of young Bangladeshi masculinity are found, a common pattern is heavy dependency on intra-ethnic networks. Negative experiences of and isolation from ‘mainstream’ society further reinforce reliance on ‘our own people’. However, acute ambivalence towards belonging to a dense Bangladeshi community exists, exemplified in the widespread denigration of the restaurant trade. Many respondents express the desire to ‘break out’ and access new experiences. The findings support current policy emphasis on ‘connecting people to work’ but highlight the more fundamental need to connect people across ethnic boundaries. The paper urges researchers to ‘unpack’ ethnicity to consider carefully what ethnic identity implies in terms of access to resources and opportunities for different individuals in different contexts in order better to understand the diversity of labour market outcomes and the persistence of disadvantage

Cryogenic 160-GHz MMIC Heterodyne Receiver Module

A cryogenic 160-GHz MMIC heterodyne receiver module has demonstrated a system noise temperature of 100 K or less at 166 GHz. This module builds upon work previously described in Development of a 150-GHz MMIC Module Prototype for Large-Scale CMB Radiation (NPO-47664), NASA Tech Briefs, Vol. 35, No. 8 (August 2011), p. 27. In the original module, the local oscillator signal was saturating the MMIC low-noise amplifiers (LNAs) with power. In order to suppress the local oscillator signal from reaching the MMIC LNAs, the W-band (75 110 GHz) signal had to be filtered out before reaching 140 170 GHz. A bandpass filter was developed to cover 120 170 GHz, using microstrip parallel-coupled lines to achieve the desired filter bandwidth, and ensure that the unwanted W-band local oscillator signal would be sufficiently suppressed. With the new bandpass filter, the entire receiver can work over the 140 180-GHz band, with a minimum system noise temperature of 460 K at 166 GHz. The module was tested cryogenically at 20 K ambient temperature, and it was found that the receiver had a noise temperature of 100 K over an 8-GHz bandwidth. The receiver module now includes a microstrip bandpass filter, which was designed to have a 3-dB bandwidth of approximately 120-170 GHz. The filter was fabricated on a 3-mil-thick alumina substrate. The filter design was based on a W-band filter design made at JPL and used in the QUIET (Q/U Imaging ExperimenT) radiometer modules. The W-band filter was scaled for a new center frequency of 150 GHz, and the microstrip segments were changed accordingly. Also, to decrease the bandwidth of the resulting scaled design, the center gaps between the microstrip lines were increased (by four micrometers in length) compared to the gaps near the edges. The use of the 150-GHz bandpass filter has enabled the receiver module to function well at room temperature. The system noise temperature was measured to be less than 600 K (at room temperature) from 154 to 168 GHz. Additionally, the use of a W-band isolator between the receiver module and the local oscillator source also improved the noise temperature substantially. This may be because the mixer was presented with a better impedance match with the use of the isolator. Cryogenic testing indicates a system noise temperature of 100 K or less at 166 GHz. Prior tests of the MMIC amplifiers alone have resulted in a system noise temperature of 65.70 K in the same frequency range (.160 GHz) when cooled to an ambient temperature of 20 K. While other detector systems may be slightly more sensitive (such as SIS mixers), they require more cooling (to 4 K ambient) and are not as easily scalable to build a large array, due to the need for large magnets and other equipment. When cooled to 20 K, this receiver module achieves approximately 100 K system noise temperature, which is slightly higher than single-amplifier module results obtained at JPL (65.70 K when an amplifier is corrected for back-end noise contributions). If this performance can be realized in practice, and a scalable array can be produced, the impact on cosmic microwave background experiments, astronomical and Earth spectroscopy, interferometry, and radio astronomy in general will be dramatic

Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy.

TRACK-HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3-Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross-sectional data from this large well-characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene-positive subjects (120 PreHD and 119 early HD) from the TRACK-HD study were included. Using voxel-based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti-saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD

Unoccupied aerial vehicles as a tool to map lizard operative temperature in tropical environments

To understand how ectotherms will respond to warming temperatures, we require information on thermal habitat quality at spatial resolutions and extents relevant to the organism. Measuring thermal habitat quality is either limited to small spatial extents, such as with ground‐based 3D operative temperature (T e ) replicas, representing the temperature of the animal at equilibrium with its environment, or is based on microclimate derived from physical models that use land cover variables and downscale coarse climate data. We draw on aspects of both these approaches and test the ability of unoccupied aerial vehicle (UAV) data (optical RGB) to predict fine‐scale heterogeneity in sub‐canopy lizard (Anolis bicaorum) T e in tropical forest using random forest models. Anolis bicaorum is an endemic, critically endangered, species, facing significant threats of habitat loss and degradation, and work was conducted as part of a larger project. Our findings indicate that a model incorporating solely air temperature, measured at the centre of the 20 × 20 m plot, and ground‐based leaf area index (LAI) measurements, measured at directly above the 3D replica, predicted T e well. However, a model with air temperature and UAV‐derived canopy metrics performed slightly better with the added advantage of enabling the mapping of T e with continuous spatial extent at high spatial resolutions, across the whole of the UAV orthomosaic, allowing us to capture and map T e across the whole of the survey plot, rather than purely at 3D replica locations. Our work provides a feasible workflow to map sub‐canopy lizard T e in tropical environments at spatial scales relevant to the organism, and across continuous areas. This can be applied to other species and can represent species within the same community that have evolved a similar thermal niche. Such methods will be imperative in risk modelling of such species to anthropogenic land cover and climate change