Development and function of group 2 innate lymphoid cells

The innate lymphoid cell (ILC) family has recently expanded with the discovery of type-2 innate lymphoid cells (ILC2). These cells arise from lymphoid progenitors in the bone marrow and, under the control of the transcriptional regulators RORα and Gata3, they mature to give rise to IL-5, IL-9 and IL-13 producing ILC2. These cells are critical components of the innate immune response to parasitic worm infections and have also been implicated in the pathogenesis of asthma and allergy. Recent advances in our understanding of the molecular regulation of ILC2 development and function now present the opportunity to develop new genetic models to assess ILC2 immune function and to investigate possible therapeutic interventions

Climate Change and the Canadian Higher Education System: An Institutional Policy Analysis

Climate change is a pressing concern. Higher education can address the challenge, but systematic analyses of climate change in education policy are sparse. This paper addresses this gap in the literature by reporting on how Canadian postsecondary educational institutions have engaged with climate change through policy actions. We used descriptive quantitative methods to analyze climate change-specific policies from a representative sample of 50 institutions across Canada and found that nearly half had some form of climate policy. Existing policies were then qualitatively analyzed. We found that the most common form of response focused on the built campus environment, with underdeveloped secondary responses focused on research, curriculum, community engagement, and governance policies. We consider the motivations for such institutional action and end with implications for policy makers and future research.  Le changement climatique est une préoccupation urgente. L’enseignement supérieur peut relever ce défi mais les analyses systématiques du changement climatique dans l’éducation sont rares.  Ce document aborde cette lacune dans la littérature en signalant comment les établissements d’enseignement postsecondaires canadiens se sont impliqués dans l’analyse du changement climatique grâce à des mesures politiques. Nous avons utilisé des méthodes quantitatives et descriptives pour analyser ces politiques de changement climatique à partir d’un échantillon représentatif de cinquante établissements canadiens et découvert que plus de la moitié possèdent une politique climatique. Nous les avons analysées de manière qualitative et trouvé que la forme de réponse la plus commune était axée sur le milieu bâti du campus avec des réponses secondaires sous-développées axées sur la recherche, le programme, la participation communautaire et la gouvernance. Nous considérons les motivations de ces mesures institutionnelles et finissons par les implications pour les décisionnaires et les  recherches futures

Evidence for changes in groundwater drought in temperate environments associated with climate change

There is currently a significant gap in our understanding of the effect of anthropogenic warming on groundwater drought. This is due to a number of factors including the limited availability of long groundwater level time series suitable for analysis, the low signal-to-noise ratios characteristic of many hydrological systems, and the infrequent nature of episodes of groundwater drought in temperate systems. Formal attribution of groundwater droughts due to anthropogenic warming is also challenging because of the potentially confounding influences of land use change and groundwater abstraction on groundwater drought. In the present study, we have not attempted to formally attribute groundwater droughts to climate change. Instead, we investigate how known centennialscale anthropogenic warming may be modifying the nature of groundwater droughts when other factors are discounted, and address the following question: how has the occurrence, duration, magnitude and intensity of groundwater drought, as expressed by changes in monthly Standardised Groundwater level Index (SGI) and in episodes of groundwater drought changed since 1891 under anthropogenic warming? Standardised indices of monthly groundwater levels (SGI), precipitation (SPI) and temperature (STI) are analysed, using two long, continuous monthly groundwater level data sets from the UK, for the period 1891 to 2015. Precipitation deficits are the main control on groundwater drought formation and propagation. However, long-term changes in groundwater drought include increases in the frequency and intensity of individual groundwater drought months, and increases in the frequency, magnitude and intensity of episodes of groundwater drought, are shown to be associated with anthropogenic warming over the study period. These is a transition from coincidence of episodes of groundwater and precipitation droughts at the end of the 19th century, to an increasing coincidence groundwater droughts with both precipitation droughts and with hot periods in the early 21st century. In the absence of long-term changes in precipitation deficits, it is inferred that the changing nature of groundwater droughts is due to changes in evapotranspiration (ET) associated with anthropogenic warming. Given the extent of shallow groundwater globally, anthropogenic warming may widely effect changes to groundwater drought characteristics in temperate environments

Soybean Marketing Methods and Characteristics of Arkansas Grain Handlers

Arkansas producers should acquaint themselves with all marketing methods available to them. Of particular importance is the pervasiveness of price risk within the current economic climate. This bulletin provides insights into the current structure of the grain marketing industry, soybean handler characteristics, and the availability and use of marketing alternatives in Arkansas. Arkansas soybean handlers were surveyed in 1998 to determine the marketing practices of both handlers and producers for the 1996 crop year. Particular emphasis was placed on the types of contracting methods offered by these handlers. Both facility size and corporate structure were found to play a significant role in determining the types of marketing contracts offered as well as the frequency of usage by producers

Protein Kinase A Activity and Anchoring Are Required for Ovarian Cancer Cell Migration and Invasion

Epithelial ovarian cancer (EOC) is the deadliest of the gynecological malignancies, due in part to its clinically occult metastasis. Therefore, understanding the mechanisms governing EOC dissemination and invasion may provide new targets for antimetastatic therapies or new methods for detection of metastatic disease. The cAMP-dependent protein kinase (PKA) is often dysregulated in EOC. Furthermore, PKA activity and subcellular localization by A-kinase anchoring proteins (AKAPs) are important regulators of cytoskeletal dynamics and cell migration. Thus, we sought to study the role of PKA and AKAP function in both EOC cell migration and invasion. Using the plasma membrane-directed PKA biosensor, pmAKAR3, and an improved migration/invasion assay, we show that PKA is activated at the leading edge of migrating SKOV-3 EOC cells, and that inhibition of PKA activity blocks SKOV-3 cell migration. Furthermore, we show that while the PKA activity within the leading edge of these cells is mediated by anchoring of type-II regulatory PKA subunits (RII), inhibition of anchoring of either RI or RII PKA subunits blocks cell migration. Importantly, we also show – for the first time – that PKA activity is up-regulated at the leading edge of SKOV-3 cells during invasion of a three-dimensional extracellular matrix and, as seen for migration, inhibition of either PKA activity or AKAP-mediated PKA anchoring blocks matrix invasion. These data are the first to demonstrate that the invasion of extracellular matrix by cancer cells elicits activation of PKA within the invasive leading edge and that both PKA activity and anchoring are required for matrix invasion. These observations suggest a role for PKA and AKAP activity in EOC metastasis

Polarization speed meter for gravitational-wave detection

We propose a modified configuration of an advanced gravitational-wave detector that is a speed-meter-type interferometer with improved sensitivity with respect to quantum noise. With the addition of polarization-controlling components to the output of an arm cavity Michelson interferometer, an orthogonal polarization state of the interferometer can be used to store signal, returning it later with opposite phase to cancel position information below the storage bandwidth of the opposite mode. This modification provides an alternative to an external kilometer-scale Fabry-Pérot cavity, as presented in earlier work of Purdue and Chen [Phys. Rev. D 66, 122004 (2002)]. The new configuration requires significantly less physical infrastructure to achieve speed meter operation. The quantity of length and alignment degrees of freedom is also reduced. We present theoretical calculations to show that such a speed meter detector is capable of beating the strain sensitivity imposed by the standard quantum limit over a broad range of frequencies for Advanced Laser Interferometer Gravitational-wave Observatory-like parameters. The benefits and possible difficulties of implementing such a scheme are outlined. We also present results for tuning of the speed meter by adjusting the degree of polarization coupling, a novel possibility that does not exist in previously proposed designs, showing that there is a smooth transition from speed meter operation to that of a signal-recycling Michelson behavior

The helminth T2 RNase v1 promotes metabolic homeostasis in an IL-33– and group 2 innate lymphoid cell–dependent mechanism

Induction of a type 2 cellular response in the white adipose tissue leads to weight loss and improves glucose homeostasis in obese animals. Injection of obese mice with recombinant helminth-derived Schistosoma mansoni egg-derived v1 (v1), a potent inducer of type 2 activation, improves metabolic status involving a mechanism reliant upon release of the type 2 initiator cytokine IL-33. IL-33 initiates the accumulation of group 2 innate lymphoid cells (ILC2s), eosinophils, and alternatively activated macrophages in the adipose tissue. IL-33 release from cells in the adipose tissue is mediated by the RNase activity of v1; however, the ability of v1 to improve metabolic status is reliant upon effective binding of v1 to CD206. We demonstrate a novel mechanism for RNasemediated release of IL-33 inducing ILC2-dependent improvements in the metabolic status of obese animals.— Hams, E., Bermingham, R., Wurlod, F. A., Hogan, A. E., O’Shea, D., Preston, R. J., Rodewald, H.-R., McKenzie, A. N. J., Fallon, P. G. The helminth T2 RNase v1 promotes metabolic homeostasis in an IL-33– and group 2 innate lymphoid cell–dependent mechanism

Changes in groundwater drought associated with anthropogenic warming

Here we present the first empirical evidence for changes in groundwater drought associated with anthropogenic warming in the absence of long-term changes in precipitation. Analysing standardised indices of monthly groundwater levels, precipitation and temperature, using two unique groundwater level data sets from the Chalk aquifer, UK, for the period 1891 to 2015, we show that precipitation deficits are the main control on groundwater drought formation and propagation. However, long-term changes in groundwater drought are shown to be associated with anthropogenic warming over the study period. These include increases in the frequency and intensity of individual groundwater drought months, and increases in the frequency, magnitude and intensity of episodes of groundwater drought, as well as an increasing tendency for both longer episodes of groundwater drought and for an increase in droughts of less than 1 year in duration. We also identify a transition from a coincidence of episodes of groundwater drought with precipitation droughts at the end of the 19th century, to an increasing coincidence with both precipitation droughts and with hot periods in the early 21st century. In the absence of long-term changes in precipitation deficits, we infer that the changing nature of groundwater droughts is due to changes in evapotranspiration (ET) associated with anthropogenic warming. We note that although the water tables are relatively deep at the two study sites, a thick capillary fringe of at least 30 m in the Chalk means that ET should not be limited by precipitation at either site. ET may be supported by groundwater through major episodes of groundwater drought and, hence, long-term changes in ET associated with anthropogenic warming may drive long-term changes in groundwater drought phenomena in the Chalk aquifer. Given the extent of shallow groundwater globally, anthropogenic warming may widely effect changes to groundwater drought characteristics in temperate environments

A Systematic Study of the In Vitro Pharmacokinetics and Estimated Human In Vivo Clearance of Indole and Indazole-3-Carboxamide Synthetic Cannabinoid Receptor Agonists Detected on the Illicit Drug Market

In vitro pharmacokinetic studies were conducted on enantiomer pairs of twelve valinate or tert-leucinate indole and indazole-3-carboxamide synthetic cannabinoid receptor agonists (SCRAs) detected on the illicit drug market to investigate their physicochemical parameters and structure-metabolism relationships (SMRs). Experimentally derived Log D7.4 ranged from 2.81 (AB-FUBINACA) to 4.95 (MDMB-4en-PINACA) and all SCRAs tested were highly protein bound, ranging from 88.9 ± 0.49% ((R)-4F-MDMB-BINACA) to 99.5 ± 0.08% ((S)-MDMB-FUBINACA). Most tested SCRAs were cleared rapidly in vitro in pooled human liver microsomes (pHLM) and pooled cryopreserved human hepatocytes (pHHeps). Intrinsic clearance (CLint) ranged from 13.7 ± 4.06 ((R)-AB-FUBINACA) to 2944 ± 95.9 mL min−1 kg−1 ((S)-AMB-FUBINACA) in pHLM, and from 110 ± 34.5 ((S)-AB-FUBINACA) to 3216 ± 607 mL min−1 kg−1 ((S)-AMB-FUBINACA) in pHHeps. Predicted Human in vivo hepatic clearance (CLH) ranged from 0.34 ± 0.09 ((S)-AB-FUBINACA) to 17.79 ± 0.20 mL min−1 kg−1 ((S)-5F-AMB-PINACA) in pHLM and 1.39 ± 0.27 ((S)-MDMB-FUBINACA) to 18.25 ± 0.12 mL min−1 kg−1 ((S)-5F-AMB-PINACA) in pHHeps. Valinate and tert-leucinate indole and indazole-3-carboxamide SCRAs are often rapidly metabolised in vitro but are highly protein bound in vivo and therefore predicted in vivo CLH is much slower than CLint. This is likely to give rise to longer detection windows of these substances and their metabolites in urine, possibly as a result of accumulation of parent drug in lipid-rich tissues, with redistribution into the circulatory system and subsequent metabolism