Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation.

Eosinophil accumulation is a prominent feature of allergic inflammatory reactions, such as those occurring in the lung of the allergic asthmatic, but the endogenous chemoattractants involved have not been identified. We have investigated this in an established model of allergic inflammation, using in vivo systems both to generate and assay relevant activity. Bronchoalveolar lavage (BAL) fluid was taken from sensitized guinea pigs at intervals after aerosol challenge with ovalbumin. BAL fluid was injected intradermally in unsensitized assay guinea pigs and the accumulation of intravenously injected 111In-eosinophils was measured. Activity was detected at 30 min after allergen challenge, peaking from 3 to 6 h and declining to low levels by 24 h. 3-h BAL fluid was purified using high performance liquid chromatography techniques in conjunction with the skin assay. Microsequencing revealed a novel protein from the C-C branch of the platelet factor 4 superfamily of chemotactic cytokines. The protein, eotaxin, exhibits homology of 53% with human MCP-1, 44% with guinea pig MCP-1, 31% with human MIP-1α, and 26% with human RANTES. Laser desorption time of flight mass analysis gave four different signals (8.15, 8.38, 8.81, and 9.03 kD), probably reflecting differential O-glycosylation. Eotaxin was highly potent, inducing substantial 111In-eosinophil accumulation at a 1-2-pmol dose in the skin, but did not induce significant 111In-neutrophil accumulation. Eotaxin was a potent stimulator of both guinea pig and human eosinophils in vitro. Human recombinant RANTES, MIP-1α, and MCP-1 were all inactive in inducing 111In-eosinophil accumulation in guinea pig skin; however, evidence was obtained that eotaxin shares a binding site with RANTES on guinea pig eosinophils. This is the first description of a potent eosinophil chemoattractant cytokine generated in vivo and suggests the possibility that similar molecules may be important in the human asthmatic lung

Three People Can Synchronize as Coupled Oscillators during Sports Activities

We experimentally investigated the synchronized patterns of three people during sports activities and found that the activity corresponded to spatiotemporal patterns in rings of coupled biological oscillators derived from symmetric Hopf bifurcation theory, which is based on group theory. This theory can provide catalogs of possible generic spatiotemporal patterns irrespective of their internal models. Instead, they are simply based on the geometrical symmetries of the systems. We predicted the synchronization patterns of rings of three coupled oscillators as trajectories on the phase plane. The interactions among three people during a 3 vs. 1 ball possession task were plotted on the phase plane. We then demonstrated that two patterns conformed to two of the three patterns predicted by the theory. One of these patterns was a rotation pattern (R) in which phase differences between adjacent oscillators were almost 2π/3. The other was a partial anti-phase pattern (PA) in which the two oscillators were anti-phase and the third oscillator frequency was dead. These results suggested that symmetric Hopf bifurcation theory could be used to understand synchronization phenomena among three people who communicate via perceptual information, not just physically connected systems such as slime molds, chemical reactions, and animal gaits. In addition, the skill level in human synchronization may play the role of the bifurcation parameter

Signal Propagation in Feedforward Neuronal Networks with Unreliable Synapses

In this paper, we systematically investigate both the synfire propagation and firing rate propagation in feedforward neuronal network coupled in an all-to-all fashion. In contrast to most earlier work, where only reliable synaptic connections are considered, we mainly examine the effects of unreliable synapses on both types of neural activity propagation in this work. We first study networks composed of purely excitatory neurons. Our results show that both the successful transmission probability and excitatory synaptic strength largely influence the propagation of these two types of neural activities, and better tuning of these synaptic parameters makes the considered network support stable signal propagation. It is also found that noise has significant but different impacts on these two types of propagation. The additive Gaussian white noise has the tendency to reduce the precision of the synfire activity, whereas noise with appropriate intensity can enhance the performance of firing rate propagation. Further simulations indicate that the propagation dynamics of the considered neuronal network is not simply determined by the average amount of received neurotransmitter for each neuron in a time instant, but also largely influenced by the stochastic effect of neurotransmitter release. Second, we compare our results with those obtained in corresponding feedforward neuronal networks connected with reliable synapses but in a random coupling fashion. We confirm that some differences can be observed in these two different feedforward neuronal network models. Finally, we study the signal propagation in feedforward neuronal networks consisting of both excitatory and inhibitory neurons, and demonstrate that inhibition also plays an important role in signal propagation in the considered networks.Comment: 33pages, 16 figures; Journal of Computational Neuroscience (published

Effects of Oxidative Stress on Behavior, Physiology, and the Redox Thiol Proteome of Caenorhabditis elegans

Accumulation of reactive oxygen species has been implicated in various diseases and aging. However, the precise physiological effects of accumulating oxidants are still largely undefined. Here, we applied a short-term peroxide stress treatment to young Caenorhabditis elegans and measured behavioral, physiological, and cellular consequences. We discovered that exposure to peroxide stress causes a number of immediate changes, including loss in mobility, decreased growth rate, and decreased cellular adenosine triphosphate levels. Many of these alterations, which are highly reminiscent of changes in aging animals, are reversible, suggesting the presence of effective antioxidant systems in young C. elegans. One of these antioxidant systems involves the highly abundant protein peroxiredoxin 2 (PRDX-2), whose gene deletion causes phenotypes symptomatic of chronic peroxide stress and shortens lifespan. Applying the quantitative redox proteomic technique OxICAT to oxidatively stressed wild-type and prdx-2 deletion worms, we identified oxidation-sensitive cysteines in 40 different proteins, including proteins involved in mobility and feeding (e.g., MYO-2 and LET-75), protein translation and homeostasis (e.g., elongation factor 1 [EFT-1] and heat shock protein 1), and adenosine triphosphate regeneration (e.g., nucleoside diphosphate kinase). The oxidative modification of some of these redox-sensitive cysteines may contribute to the physiological and behavioral changes observed in oxidatively stressed animals. Antioxid. Redox Signal. 14, 1023-1037.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90439/1/ars-2E2010-2E3203.pd

A Comparative Look at Various Countries\u27 Legal Regimes Governing Automated Vehicles

News and commentary about automated vehicles (AVs) focus on how they look and appear to operate, along with the companies developing and testing them. Behind the scenes are legal regimes—laws, regulations, and implementing bodies of different kinds—that literally and figuratively provide the rules of the road for AVs. Legal regimes matter because public welfare hinges on aspects of AV design and operation. Legal regimes can provide gatekeeping for AV developers and operators seeking to use public roads, and they can allocate liability when something goes wrong. Guiding and complementing legal regimes is public policy. Policy documents such as articulations of national strategies are sometimes used to address issues related to legal regimes and to demonstrate a jurisdiction’s support for AV development. Building on its long history analyzing AV policy issues, RAND (with support of its Institute for Civil Justice) collaborated with the University of Michigan Law School’s Law and Mobility Program to study the nature of different AV legal regimes around the world. It selected countries known to be active in this domain. The research team reviewed and shared scholarly and gray literature (which is a type of scholarship produced by an entity in which commercial publications are not the primary focus, such as white papers from a government agency), and it also consulted experts in these regimes from the public and private sectors. Under the supervision of the Law and Mobility Fellow (a lawyer), law students collected and studied materials associated with country-specific legal regimes and drafted summaries guided by RAND’s enumeration of key factors. Availability of information about legal regimes varies—access to documentation, especially in English, is uneven, even for officials in different countries working collaboratively on these issues. That constrained availability is reflected in published legal comparisons, and it motivated the research team’s systematic research, which drew from materials in English and other languages. This article summarizes the makeup of AV legal regimes of Australia, China, France, Germany, Japan, and the United Kingdom. It highlights some key contrasts, which will be developed further as the project continues. It focuses on law and policy relating to highly to fully automated vehicles (SAE Levels 4 and 5). Although guided by a common set of topics for each country, each profile reflects the material available and the factors that differentiate national approaches. The remainder of this article introduces the legal regimes of the covered countries in turn. It then provides an overview of key points of comparison and outlines future work

Backbone and side chain 1H, 15N and 13C assignments for a thiol-disulphide oxidoreductase from the Antarctic bacterium Pseudoalteromonas haloplanktis TAC125

Enzymes produced by psychrophilic organisms have successfully overcome the low temperature challenge and evolved to maintain high catalytic rates in their permanently cold environments. As an initial step in our attempt to elucidate the cold-adaptation strategies used by these enzymes we report here the 1H, 15N and 13C assignments for the reduced form of a thiol-disulphide oxidoreductase from the Antarctic bacterium Pseudoalteromonas haloplanktis TAC125.The NMR spectrometers are part of The National NMR Network (REDE/1517/RMN/2005), supported by ‘‘Programa Operacional Ciência e Inovação (POCTI) 2010’’ and Fundação para a Ciência e a Tecnologia (FCT). This work was funded by FCT, POCTI and FEDER; Projects POCI/BIA-PRO/57263/2004 and PTDC/BIO/70806/2006. TC is holder of a long term EMBO fellowship. MM is thankful to the Fundação para a Ciência e Tecnologia for its support through Programa Ciência 2007.info:eu-repo/semantics/publishedVersio

Randomized controlled trial of a good practice approach to treatment of childhood obesity in Malaysia: Malaysian childhood obesity treatment trial (MASCOT)

Context. Few randomized controlled trials (RCTs) of interventions for the treatment of childhood obesity have taken place outside the Western world. Aim. To test whether a good practice intervention for the treatment of childhood obesity would have a greater impact on weight status and other outcomes than a control condition in Kuala Lumpur, Malaysia. Methods. Assessor-blinded RCT of a treatment intervention in 107 obese 7- to 11-year olds. The intervention was relatively low intensity (8 hours contact over 26 weeks, group based), aiming to change child sedentary behavior, physical activity, and diet using behavior change counselling. Outcomes were measured at baseline and six months after the start of the intervention. Primary outcome was BMI z-score, other outcomes were weight change, health-related quality of life (Peds QL), objectively measured physical activity and sedentary behavior (Actigraph accelerometry over 5 days). Results. The intervention had no significant effect on BMI z score relative to control. Weight gain was reduced significantly in the intervention group compared to the control group (+1.5 kg vs. +3.5 kg, respectively, t-test p < 0.01). Changes in health-related quality of life and objectively measured physical activity and sedentary behavior favored the intervention group. Conclusions. Treatment was associated with reduced rate of weight gain, and improvements in physical activity and quality of life. More substantial benefits may require longer term and more intensive interventions which aim for more substantive lifestyle changes

Access Anglesey 2018: Lessons from an inclusive field course

Abstract. Traditional methods of fieldwork delivery can present learners with a range of physical, cognitive and social challenges which may subsequently hinder their ability to engage effectively with learning. We developed a residential geoscience field course designed to be physically accessible to, and socially inclusive of, a diverse range of learners including those with limited physical mobility and neurodiverse conditions. This paper presents the logistical and pedagogical challenges involved in delivering such a field course. In terms of pedagogic design scheduling, pace and timing, and the ability to access content in multiple ways were critical to ensuring that all students were included in the learning. The most effective mitigations were the simplest and benefitted the whole group. Practical interventions found to support access and inclusion for the benefit of all participants included using an audio tour-guide system to communicate with students at field locations, using a four-wheel drive vehicle to improve access to specific locations, providing alternative exercises such as prepared photomicrographs and rock specimens, providing electronic tablets with suitable apps, and selecting accommodation with accessible common-room spaces, and a dedicated quiet room. </jats:p

Issues of methods and interpretation in the National Cancer Institute formaldehyde cohort study

In 2004, the International Agency for Research on Cancer (IARC) reclassified formaldehyde (FA) from a probable (Group 2A) to a known human carcinogen (Group 1) citing results for nasopharyngeal cancer (NPC) mortality from the follow-up through 1994 of the National Cancer Institute formaldehyde cohort study. To the contrary, in 2012, the Committee for Risk Assessment of the European Chemicals Agency disagreed with the proposal to classify FA as a known human carcinogen (Carc. 1A), proposing a lower but still protective category, namely as a substance which is presumed to have carcinogenic potential for humans (Carc. 1B). Thus, U.S. and European regulatory agencies currently disagree about the potential human carcinogenicity of FA. In 2013, the National Cancer Institute reported results from their follow-up through 2004 of the formaldehyde cohort and concluded that the results continue to suggest a link between FA exposure and NPC. We discuss in this commentary why we believe that this interpretation is neither consistent with the available data from the most recent update of the National Cancer Institute cohort study nor with other research findings from that cohort, other large cohort studies and the series of publications by some of the current authors, including an independent study of one of the National Cancer Institute's study plants. Another serious concern relates to the incorrectness of the data from the follow-up through 1994 of the National Cancer Institute study stemming from incomplete mortality ascertainment. While these data were corrected by the National Cancer Institute in subsequent supplemental publications, incorrect data from the original publications have been cited extensively in recent causal evaluations of FA, including IARC. We conclude that the NCI publications that contain incorrect data from the incomplete 1994 mortality follow-up should be retracted entirely or corrected via published errata in the corresponding journals, and efforts should be made to re-analyze data from the 2004 follow-up of the NCI cohort study. © 2014 Marsh et al.; licensee BioMed Central Ltd

Feeding spectra and activity of the freshwater crab Trichodactylus kensleyi (Decapoda: Brachyura: Trichodactylidae) at La Plata basin

Background: In inland water systems, it is important to characterize the trophic links in order to identify the ‘trophic species’ and, from the studies of functional diversity, understand the dynamics of matter and energy in these environments. The aim of this study is to analyze the natural diet of Trichodactylus kensleyi of subtropical rainforest streams and corroborate the temporal variation in the trophic activity during day hours. Results: A total of 15 major taxonomic groups were recognized in gut contents. The index of relative importance identified the following main prey items in decreasing order of importance: vegetal remains, oligochaetes, chironomid larvae, and algae. A significant difference was found in the amount of full stomachs during day hours showing a less trophic activity at midday and afternoon. The index of relative importance values evidenced the consumption of different prey according to day moments. Results of the gut content indicate that T. kensleyi is an omnivorous crab like other trichodactylid species. Opportunistic behavior is revealed by the ingestion of organisms abundant in streams such as oligochaetes and chironomid larvae. The consumption of allochthonous plant debris shows the importance of this crab as shredder in subtropical streams. However, the effective assimilation of plant matter is yet unknown in trichodactylid crabs. Conclusions: This research provides knowledge that complements previous studies about trophic relationships of trichodactylid crabs and supported the importance of T. kensleyi in the transference of energy and matter from benthic community and riparian sources to superior trophic levels using both macro- and microfauna.Fil: Williner, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Humanidades y Ciencias; ArgentinaFil: de Azevedo Carvalho, Debora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Collins, Pablo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin