Grip Force Reveals the Context Sensitivity of Language-Induced Motor Activity during “Action Words

Studies demonstrating the involvement of motor brain structures in language processing typically focus on \ud time windows beyond the latencies of lexical-semantic access. Consequently, such studies remain inconclusive regarding whether motor brain structures are recruited directly in language processing or through post-linguistic conceptual imagery. In the present study, we introduce a grip-force sensor that allows online measurements of language-induced motor activity during sentence listening. We use this tool to investigate whether language-induced motor activity remains constant or is modulated in negative, as opposed to affirmative, linguistic contexts. Our findings demonstrate that this simple experimental paradigm can be used to study the online crosstalk between language and the motor systems in an ecological and economical manner. Our data further confirm that the motor brain structures that can be called upon during action word processing are not mandatorily involved; the crosstalk is asymmetrically\ud governed by the linguistic context and not vice versa

Binding Site Alteration Is Responsible for Field-Isolated Resistance to Bacillus thuringiensis Cry2A Insecticidal Proteins in Two Helicoverpa Species

Background Evolution of resistance by target pests is the main threat to the long-term efficacy of crops expressing Bacillus thuringiensis (Bt) insecticidal proteins. Cry2 proteins play a pivotal role in current Bt spray formulations and transgenic crops and they complement Cry1A proteins because of their different mode of action. Their presence is critical in the control of those lepidopteran species, such as Helicoverpa spp., which are not highly susceptible to Cry1A proteins. In Australia, a transgenic variety of cotton expressing Cry1Ac and Cry2Ab (Bollgard II) comprises at least 80% of the total cotton area. Prior to the widespread adoption of Bollgard II, the frequency of alleles conferring resistance to Cry2Ab in field populations of Helicoverpa armigera and Helicoverpa punctigera was significantly higher than anticipated. Colonies established from survivors of F2 screens against Cry2Ab are highly resistant to this toxin, but susceptible to Cry1Ac. Methodology/Principal Findings Bioassays performed with surface-treated artificial diet on neonates of H. armigera and H. punctigera showed that Cry2Ab resistant insects were cross-resistant to Cry2Ae while susceptible to Cry1Ab. Binding analyses with 125I-labeled Cry2Ab were performed with brush border membrane vesicles from midguts of Cry2Ab susceptible and resistant insects. The results of the binding analyses correlated with bioassay data and demonstrated that resistant insects exhibited greatly reduced binding of Cry2Ab toxin to midgut receptors, whereas no change in 125I-labeled-Cry1Ac binding was detected. As previously demonstrated for H. armigera, Cry2Ab binding sites in H. punctigera were shown to be shared by Cry2Ae, which explains why an alteration of the shared binding site would lead to cross-resistance between the two Cry2A toxins. Conclusion/Significance This is the first time that a mechanism of resistance to the Cry2 class of insecticidal proteins has been reported. Because we found the same mechanism of resistance in multiple strains representing several field populations, we conclude that target site alteration is the most likely means that field populations evolve resistance to Cry2 proteins in Helicoverpa spp. Our work also confirms the presence in the insect midgut of specific binding sites for this class of proteins. Characterizing the Cry2 receptors and their mutations that enable resistance could lead to the development of molecular tools to monitor resistance in the [email protected]; [email protected]

BCR-ABL1-independent PI3Kinase activation causing imatinib-resistance

<p>Abstract</p> <p>Background</p> <p>The <it>BCR-ABL1 </it>translocation occurs in chronic myeloid leukemia (CML) and in 25% of cases with acute lymphoblastic leukemia (ALL). The advent of tyrosine kinase inhibitors (TKI) has fundamentally changed the treatment of CML. However, TKI are not equally effective for treating ALL. Furthermore, <it>de novo </it>or <it>secondary </it>TKI-resistance is a significant problem in CML. We screened a panel of <it>BCR-ABL1 </it>positive ALL and CML cell lines to find models for imatinib-resistance.</p> <p>Results</p> <p>Five of 19 <it>BCR-ABL1 </it>positive cell lines were resistant to imatinib-induced apoptosis (KCL-22, MHH-TALL1, NALM-1, SD-1, SUP-B15). None of the resistant cell lines carried mutations in the kinase domain of <it>BCR-ABL1 </it>and all showed resistance to second generation TKI, nilotinib or dasatinib. STAT5, ERK1/2 and the ribosomal S6 protein (RPS6) are <it>BCR-ABL1 </it>downstream effectors, and all three proteins are dephosphorylated by imatinib in sensitive cell lines. TKI-resistant phosphorylation of RPS6, but responsiveness as regards JAK/STAT5 and ERK1/2 signalling were characteristic for resistant cell lines. PI3K pathway inhibitors effected dephosphorylation of RPS6 in imatinib-resistant cell lines suggesting that an oncogene other than <it>BCR-ABL1 </it>might be responsible for activation of the PI3K/AKT1/mTOR pathway, which would explain the TKI resistance of these cells. We show that the TKI-resistant cell line KCL-22 carries a PI3Kα E545G mutation, a site critical for the constitutive activation of the PI3K/AKT1 pathway. Apoptosis in TKI-resistant cells could be induced by inhibition of AKT1, but not of mTOR.</p> <p>Conclusion</p> <p>We introduce five Philadelphia-chromosome positive cell lines as TKI-resistance models. None of these cell lines carries mutations in the kinase domain of <it>BCR-ABL1 </it>or other molecular aberrations previously indicted in the context of imatinib-resistance. These cell lines are unique as they dephosphorylate ERK1/2 and STAT5 after treatment with imatinib, while PI3K/AKT1/mTOR activity remains unaffected. Inhibition of AKT1 leads to apoptosis in the imatinib-resistant cell lines. In conclusion, Ph+ cell lines show a form of imatinib-resistance attributable to constitutive activation of the PI3K/AKT1 pathway. Mutations in <it>PIK3CA</it>, as observed in cell line KCL-22, or PI3K activating oncogenes may undelie TKI-resistance in these cell lines.</p

The Political Economy of Non-Traditional Security: Explaining the Governance of Avian Influenza in Indonesia

Given the common association of non-traditional security (NTS) problems with globalisation, surprisingly little attention has been paid to how the political economy context of given NTS issues shape how they are securitised and managed in practice. We argue that security and its governance are always highly contested because different modes of security governance invariably privilege particular interests and normative agendas in state and society, which relate directly to the political economy. Drawing on critical political geography, we argue that, because NTS issues are perceived as at least potentially transnational, their securitisation often involves strategic attempts by actors and coalitions to ‘rescale’ their governance beyond the national political and institutional arenas, into new, expert-dominated modes of governance. Such efforts are often resisted by other coalitions, for which this rescaling is deleterious. As evidenced by a case study of avian influenza in Indonesia, particular governance outcomes depend upon the nature of the coalitions assembled for and against rescaling in specific situations, while these coalitions’ make-up and relative strength is shaped by the political economy of the industries that rescaling would affect, viewed against the broader backdrop of state-society relations

A reliable cw Lyman-α\alpha laser source for future cooling of antihydrogen

We demonstrate a reliable continuous-wave (cw) laser source at the 1\,$S$--2\,$P$ transition in (anti)hydrogen at 121.56\,nm (Lyman-$\alpha$) based on four-wave sum-frequency mixing in mercury. A two-photon resonance in the four-wave mixing scheme is essential for a powerful cw Lyman-$\alpha$ source and is well investigated.Comment: 8 pages, 3 figures, Proceedings of LEAP 201

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

High-quality habitat and facilitation ameliorate competitive effects of prior residents on new settlers

Many species disperse during their lifetime. Two factors that can affect the performance of individuals following dispersal are the presence of conspecifics and intrinsic habitat quality at the settlement site. Detecting the influence of these factors can be difficult for at least two reasons: (1) the outcomes of interactions with conspecifics are often variable including both competition and facilitation, and (2) selection of high quality habitats often leads to positive covariance between habitat quality and density. In this study, I investigate positive and negative effects of resident blue streak cleaner wrasse (Labroides dimidiatus) on the growth and survival of recently settled conspecifics while accounting for habitat quality. Juvenile L. dimidiatus settle near adult conspecifics, but likely have to compete with resident adults for access to food. However, field experiments indicate that settlers have access to more resources at occupied sites, and as a result, grow faster despite evidence for competition with residents. This result is a direct consequence of two factors: (1) resident conspecifics facilitate settlers by attracting client fish, and (2) resident conspecifics are strongly associated with high quality habitat. These results highlight the need to simultaneously consider habitat quality and competitive and facilitative interactions between conspecifics when making inferences about ecological processes from spatial patterns of individual performance

Networked T Cell Death following Macrophage Infection by Mycobacterium tuberculosis

<div><h3>Background</h3><p>Depletion of T cells following infection by <em>Mycobacterium tuberculosis</em> (Mtb) impairs disease resolution, and interferes with clinical test performance that relies on cell-mediated immunity. A number of mechanisms contribute to this T cell suppression, such as activation-induced death and trafficking of T cells out of the peripheral circulation and into the diseased lungs. The extent to which Mtb infection of human macrophages affects T cell viability however, is not well characterised.</p> <h3>Methodology/Principal Findings</h3><p>We found that lymphopenia (<1.5×10⁹ cells/l) was prevalent among culture-positive tuberculosis patients, and lymphocyte counts significantly improved post-therapy. We previously reported that Mtb-infected human macrophages resulted in death of infected and uninfected bystander macrophages. In the current study, we sought to examine the influence of infected human alveolar macrophages on T cells. We infected primary human alveolar macrophages (the primary host cell for Mtb) or PMA-differentiated THP-1 cells with Mtb H37Ra, then prepared cell-free supernatants. The supernatants of Mtb-infected macrophages caused dose-dependent, caspase-dependent, T cell apoptosis. This toxic effect of infected macrophage secreted factors did not require TNF-α or Fas. The supernatant cytotoxic signal(s) were heat-labile and greater than 50 kDa in molecular size. Although ESAT-6 was toxic to T cells, other Mtb-secreted factors tested did not influence T cell viability; nor did macrophage-free Mtb bacilli or broth from Mtb cultures. Furthermore, supernatants from <em>Mycobacterium bovis</em> Bacille de Calmette et Guerin (BCG)- infected macrophages also elicited T cell death suggesting that ESAT-6 itself, although cytotoxic, was not the principal mediator of T cell death in our system.</p> <h3>Conclusions</h3><p>Mtb-Infected macrophages secrete heat-labile factors that are toxic to T cells, and may contribute to the immunosuppression seen in tuberculosis as well as interfere with microbial eradication in the granuloma.</p> </div

Neighborhood socioeconomic status, Medicaid coverage and medical management of myocardial infarction: Atherosclerosis risk in communities (ARIC) community surveillance

<p>Abstract</p> <p>Background</p> <p>Pharmacologic treatments are efficacious in reducing post-myocardial infarction (MI) morbidity and mortality. The potential influence of socioeconomic factors on the receipt of pharmacologic therapy has not been systematically examined, even though healthcare utilization likely influences morbidity and mortality post-MI. This study aims to investigate the association between socioeconomic factors and receipt of evidence-based treatments post-MI in a community surveillance setting.</p> <p>Methods</p> <p>We evaluated the association of census tract-level neighborhood household income (nINC) and Medicaid coverage with pharmacologic treatments (aspirin, beta [β]-blockers and angiotensin converting enzyme [ACE] inhibitors; optimal therapy, defined as receipt of two or more treatments) received during hospitalization or at discharge among 9,608 MI events in the ARIC community surveillance study (1993-2002). Prevalence ratios (PR, 95% CI), adjusted for the clustering of hospitalized MI events within census tracts and within patients, were estimated using Poisson regression.</p> <p>Results</p> <p>Seventy-eight percent of patients received optimal therapy. Low nINC was associated with a lower likelihood of receiving β-blockers (0.93, 0.87-0.98) and a higher likelihood of receiving ACE inhibitors (1.13, 1.04-1.22), compared to high nINC. Patients with Medicaid coverage were less likely to receive aspirin (0.92, 0.87-0.98), compared to patients without Medicaid coverage. These findings were independent of other key covariates.</p> <p>Conclusions</p> <p>nINC and Medicaid coverage may be two of several socioeconomic factors influencing the complexities of medical care practice patterns.</p

Corporate philanthropy, political influence, and health policy

Background The Framework Convention of Tobacco Control (FCTC) provides a basis for nation states to limit the political effects of tobacco industry philanthropy, yet progress in this area is limited. This paper aims to integrate the findings of previous studies on tobacco industry philanthropy with a new analysis of British American Tobacco's (BAT) record of charitable giving to develop a general model of corporate political philanthropy that can be used to facilitate implementation of the FCTC. Method Analysis of previously confidential industry documents, BAT social and stakeholder dialogue reports, and existing tobacco industry document studies on philanthropy. Results The analysis identified six broad ways in which tobacco companies have used philanthropy politically: developing constituencies to build support for policy positions and generate third party advocacy; weakening opposing political constituencies; facilitating access and building relationships with policymakers; creating direct leverage with policymakers by providing financial subsidies to specific projects; enhancing the donor's status as a source of credible information; and shaping the tobacco control agenda by shifting thinking on the importance of regulating the market environment for tobacco and the relative risks of smoking for population health. Contemporary BAT social and stakeholder reports contain numerous examples of charitable donations that are likely to be designed to shape the tobacco control agenda, secure access and build constituencies. Conclusions and Recommendations Tobacco companies' political use of charitable donations underlines the need for tobacco industry philanthropy to be restricted via full implementation of Articles 5.3 and 13 of the FCTC. The model of tobacco industry philanthropy developed in this study can be used by public health advocates to press for implementation of the FCTC and provides a basis for analysing the political effects of charitable giving in other industry sectors which have an impact on public health such as alcohol and food