102 research outputs found

    Multimodal Chemosensory Integration through the Maxillary Palp in Drosophila

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    Drosophila melanogaster has an olfactory organ called the maxillary palp. It is smaller and numerically simpler than the antenna, and its specific role in behavior has long been unclear. Because of its proximity to the mouthparts, I explored the possibility of a role in taste behavior. Maxillary palp was tuned to mediate odor-induced taste enhancement: a sucrose solution was more appealing when simultaneously presented with the odorant 4-methylphenol. The same result was observed with other odors that stimulate other types of olfactory receptor neuron in the maxillary palp. When an antennal olfactory receptor was genetically introduced in the maxillary palp, the fly interpreted a new odor as a sweet-enhancing smell. These results all point to taste enhancement as a function of the maxillary palp. It also opens the door for studying integration of multiple senses in a model organism

    Tumor Suppressor Protein p53 Recruits Human Sin3B/HDAC1 Complex for Down-Regulation of Its Target Promoters in Response to Genotoxic Stress

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    Master regulator protein p53, popularly known as the “guardian of genome” is the hub for regulation of diverse cellular pathways. Depending on the cell type and severity of DNA damage, p53 protein mediates cell cycle arrest or apoptosis, besides activating DNA repair, which is apparently achieved by regulation of its target genes, as well as direct interaction with other proteins. p53 is known to repress target genes via multiple mechanisms one of which is via recruitment of chromatin remodelling Sin3/HDAC1/2 complex. Sin3 proteins (Sin3A and Sin3B) regulate gene expression at the chromatin-level by serving as an anchor onto which the core Sin3/HDAC complex is assembled. The Sin3/HDAC co-repressor complex can be recruited by a large number of DNA-binding transcription factors. Sin3A has been closely linked to p53 while Sin3B is considered to be a close associate of E2Fs. The theme of this study was to establish the role of Sin3B in p53-mediated gene repression. We demonstrate a direct protein-protein interaction between human p53 and Sin3B (hSin3B). Amino acids 1–399 of hSin3B protein are involved in its interaction with N-terminal region (amino acids 1–108) of p53. Genotoxic stress induced by Adriamycin treatment increases the levels of hSin3B that is recruited to the promoters of p53-target genes (HSPA8, MAD1 and CRYZ). More importantly recruitment of hSin3B and repression of the three p53-target promoters upon Adriamycin treatment were observed only in p53+/+ cell lines. Additionally an increased tri-methylation of the H3K9 residue at the promoters of HSPA8 and CRYZ was also observed following Adriamycin treatment. The present study highlights for the first time the essential role of Sin3B as an important associate of p53 in mediating the cellular responses to stress and in the transcriptional repression of genes encoding for heat shock proteins or proteins involved in regulation of cell cycle and apoptosis

    NOV story: the way to CCN3

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    The principal aim of this historical review- the first in a new series- is to present the basic concepts that led to the discovery of NOV and to show how our ideas evolved regarding the role and functions of this new class of proteins. It should prove particularly useful to the new comers and to students who are engaged in this exciting field. It is also a good opportunity to acknowledge the input of those who participated in the development of this scientific endeavou

    A Novel Intravital Method to Evaluate Cerebral Vasospasm in Rat Models of Subarachnoid Hemorrhage: A Study with Synchrotron Radiation Angiography

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    Precise in vivo evaluation of cerebral vasospasm caused by subarachnoid hemorrhage has remained a critical but unsolved issue in experimental small animal models. In this study, we used synchrotron radiation angiography to study the vasospasm of anterior circulation arteries in two subarachnoid hemorrhage models in rats. Synchrotron radiation angiography, laser Doppler flowmetry-cerebral blood flow measurement, [125I]N-isopropyl-p-iodoamphetamine cerebral blood flow measurement and terminal examinations were applied to evaluate the changes of anterior circulation arteries in two subarachnoid hemorrhage models made by blood injection into cisterna magna and prechiasmatic cistern. Using synchrotron radiation angiography technique, we detected cerebral vasospasm in subarachnoid hemorrhage rats compared to the controls (p<0.05). We also identified two interesting findings: 1) both middle cerebral artery and anterior cerebral artery shrunk the most at day 3 after subarachnoid hemorrhage; 2) the diameter of anterior cerebral artery in the prechiasmatic cistern injection group was smaller than that in the cisterna magna injection group (p<0.05), but not for middle cerebral artery. We concluded that synchrotron radiation angiography provided a novel technique, which could directly evaluate cerebral vasospasm in small animal experimental subarachnoid hemorrhage models. The courses of vasospasm in these two injection models are similar; however, the model produced by prechiasmatic cistern injection is more suitable for study of anterior circulation vasospasm

    Inappropriate stereotypical inferences? An adversarial collaboration in experimental ordinary language philosophy

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    This paper trials new experimental methods for the analysis of natural language reasoning and the (re)development of critical ordinary language philosophy in the wake of J.L. Austin. Philosophical arguments and thought experiments are strongly shaped by default pragmatic inferences, including stereotypical inferences. Austin suggested that contextually inappropriate stereotypical inferences are at the root of some philosophical paradoxes and problems, and that these can be resolved by exposing those verbal fallacies. This paper builds on recent efforts to empirically document inappropriate stereotypical inferences that may drive philosophical arguments. We demonstrate that previously employed questionnaire-based output measures do not suffice to exclude relevant confounds. We then report an experiment that combines reading time measurements with plausibility ratings. The study seeks to provide evidence of inappropriate stereotypical inferences from appearance verbs that have been suggested to lie at the root of the influential ‘argument from illusion’. Our findings support a diagnostic reconstruction of this argument. They provide the missing component for proof of concept for an experimental implementation of critical ordinary language philosophy that is in line with the ambitions of current ‘evidential’ experimental philosophy

    Life cycle assessment of European anchovy (Engraulis encrasicolus) landed by purse seine vessels in northern Spain

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    Purpose: The main purpose of this article is to assess the environmental impacts associated with the fishing operations related to European anchovy fishing in Cantabria (northern Spain) under a life cycle approach. Methods: The life cycle assessment (LCA) methodology was applied for this case study including construction, maintenance, use, and end of life of the vessels. The functional unit used was 1 kg of landed round anchovy at port. Inventory data were collected for the main inputs and outputs of 32 vessels, representing a majority of vessels in the fleet. Results and discussion: Results indicated, in a similar line to what is reported in the literature, that the production, transportation, and use of diesel were the main environmental hot spots in conventional impact categories. Moreover, in this case, the production and transportation of seine nets was also relevant. Impacts linked to greenhouse gas (GHG) emissions suggest that emissions were in the upper range for fishing species captured with seine nets and the value of global warming potential (GWP) was 1.44 kg CO2 eq per functional unit. The ecotoxicity impacts were mainly due to the emissions of antifouling substances to the ocean. Regarding fishery-specific categories, many were discarded given the lack of detailed stock assessments for this fishery. Hence, only the biotic resource use category was computed, demonstrating that the ecosystems' effort to sustain the fishery is relatively low. Conclusions: The use of the LCA methodology allowed identifying the main environmental hot spots of the purse seining fleet targeting European anchovy in Cantabria. Individualized results per port or per vessel suggested that there are significant differences in GHG emissions between groups. In addition, fuel use is high when compared to similar fisheries. Therefore, research needs to be undertaken to identify why fuel use is so high, particularly if it is related to biomass and fisheries management or if skipper decisions could play a role.The authors thank the Ministry of Economy and Competitiveness of the Spanish Government for their financial support via the project GeSAC-Conserva: Sustainable Management of the Cantabrian Anchovies (CTM2013-43539-R) and to Pedro Villanueva-Rey for valuable scientific exchange. Jara Laso thanks the Ministry of Economy and Competitiveness of Spanish Government for their financial support via the research fellowship BES-2014-069368 and to the Ministry of Rural Environment, Fisheries and Food of Cantabria for the data support. Dr. Ian VĂĄzquez-Rowe thanks the Peruvian LCA Network for operational support. Reviewers are also thanked for the valuable and detailed suggestions. The work of Dr. Rosa M. Crujeiras has been funded by MTM2016-76969P (AEI/FEDER, UE)

    Trends in future health financing and coverage: future health spending and universal health coverage in 188 countries, 2016–40

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    This online publication has been corrected. The corrected version first appeared at thelancet.com on May 3, 2018© 2018 The Author(s). Background: Achieving universal health coverage (UHC) requires health financing systems that provide prepaid pooled resources for key health services without placing undue financial stress on households. Understanding current and future trajectories of health financing is vital for progress towards UHC. We used historical health financing data for 188 countries from 1995 to 2015 to estimate future scenarios of health spending and pooled health spending through to 2040. Methods: We extracted historical data on gross domestic product (GDP) and health spending for 188 countries from 1995 to 2015, and projected annual GDP, development assistance for health, and government, out-of-pocket, and prepaid private health spending from 2015 through to 2040 as a reference scenario. These estimates were generated using an ensemble of models that varied key demographic and socioeconomic determinants. We generated better and worse alternative future scenarios based on the global distribution of historic health spending growth rates. Last, we used stochastic frontier analysis to investigate the association between pooled health resources and UHC index, a measure of a country's UHC service coverage. Finally, we estimated future UHC performance and the number of people covered under the three future scenarios. Findings: In the reference scenario, global health spending was projected to increase from US10trillion(9510 trillion (95% uncertainty interval 10 trillion to 10 trillion) in 2015 to 20 trillion (18 trillion to 22 trillion) in 2040. Per capita health spending was projected to increase fastest in upper-middle-income countries, at 4·2% (3·4–5·1) per year, followed by lower-middle-income countries (4·0%, 3·6–4·5) and low-income countries (2·2%, 1·7–2·8). Despite global growth, per capita health spending was projected to range from only 40(24–65)to40 (24–65) to 413 (263–668) in 2040 in low-income countries, and from 140(90–200)to140 (90–200) to 1699 (711–3423) in lower-middle-income countries. Globally, the share of health spending covered by pooled resources would range widely, from 19·8% (10·3–38·6) in Nigeria to 97·9% (96·4–98·5) in Seychelles. Historical performance on the UHC index was significantly associated with pooled resources per capita. Across the alternative scenarios, we estimate UHC reaching between 5·1 billion (4·9 billion to 5·3 billion) and 5·6 billion (5·3 billion to 5·8 billion) lives in 2030. Interpretation: We chart future scenarios for health spending and its relationship with UHC. Ensuring that all countries have sustainable pooled health resources is crucial to the achievement of UHC.The Bill & Melinda Gates Foundation
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