153 research outputs found

    The Judicialization of Politics in Israel

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    One of the central debates on the Israeli political scene in 2005 was the public controversy between the President of the Supreme Court, Aharon Barak, and the Minister of Justice, Tzipi Livni, on the nomination of three new justices to the Supreme Court. This controversy focused on Law professor Ruth Gavison, whose nomination Barak opposed because of her vehement criticism of the political orientation and judicial activism of the Supreme Court, which many observers attribute to Barak himself...

    The Judicialization of Politics in Israel

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    One of the central debates on the Israeli political scene in 2005 was the public controversy between the President of the Supreme Court, Aharon Barak, and the Minister of Justice, Tzipi Livni, on the nomination of three new justices to the Supreme Court. This controversy focused on Law professor Ruth Gavison, whose nomination Barak opposed because of her vehement criticism of the political orientation and judicial activism of the Supreme Court, which many observers attribute to Barak himself...

    The potential impact of media reporting in syndromic surveillance: an example using a possible Cryptosporidium exposure in North West England, August to September 2015

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    During August 2015, a boil water notice (BWN) was issued across parts of North West England following the detection of Cryptosporidium oocysts in the public water supply. Using prospective syndromic surveillance, we detected statistically significant increases in the presentation of cases of gastroenteritis and diarrhoea to general practitioner services and related calls to the national health telephone advice service in those areas affected by the BWN. In the affected areas, average in-hours general practitioner consultations for gastroenteritis increased by 24.8% (from 13.49 to 16.84) during the BWN period; average diarrhoea consultations increased by 28.5% (from 8.33 to 10.71). Local public health investigations revealed no laboratory reported cases confirmed as being associated with the water supply. These findings suggest that the increases reported by syndromic surveillance of cases of gastroenteritis and diarrhoea likely resulted from changes in healthcare seeking behaviour driven by the intense local and national media coverage of the potential health risks during the event. This study has further highlighted the potential for media-driven bias in syndromic surveillance, and the challenges in disentangling true increases in community infection from those driven by media reporting

    Evaluating Medicinal Plants for Anticancer Activity

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    Plants have been used for medical purposes since the beginning of human history and are the basis of modern medicine. Most chemotherapeutic drugs for cancer treatment are molecules identified and isolated from plants or their synthetic derivatives. Our hypothesis was that whole plant extracts selected according to ethnobotanical sources of historical use might contain multiple molecules with antitumor activities that could be very effective in killing human cancer cells. This study examined the effects of three whole plant extracts (ethanol extraction) on human tumor cells. The extracts were from Urtica membranacea (Urticaceae), Artemesia monosperma (Asteraceae), and Origanum dayi post (Labiatae). All three plant extracts exhibited dose- and time-dependent killing capabilities in various human derived tumor cell lines and primary cultures established from patients’ biopsies. The killing activity was specific toward tumor cells, as the plant extracts had no effect on primary cultures of healthy human cells. Cell death caused by the whole plant extracts is via apoptosis. Plant extract 5 (Urtica membranacea) showed particularly strong anticancer capabilities since it inhibited actual tumor progression in a breast adenocarcinoma mouse model. Our results suggest that whole plant extracts are promising anticancer reagents

    A Screening Pipeline for Antiparasitic Agents Targeting Cryptosporidium Inosine Monophosphate Dehydrogenase

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    Persistent diarrhea is a leading cause of illness and death among impoverished children, and a growing share of this disease burden can be attributed to the parasite Cryptosporidium. There are no vaccines to prevent Cryptosporidium infection, and the treatment options are limited and unreliable. Critically, no effective treatment exists for children or adults suffering from AIDS. Cryptosporidium presents many technical obstacles for drug discovery; perhaps the most important roadblock is the difficulty of monitoring drug action. Here we have developed a set of methods to accelerate the drug discovery process for cryptosporidiosis. We exploit the opportunities for experimental manipulation in the related parasite Toxoplasma to genetically engineer a Cryptosporidium model. This new model parasite mirrors the metabolism of Cryptosporidium for a particularly promising drug target that supplies the building blocks for DNA and RNA. Drug effectiveness can be assayed through simple fluorescence measurements for many candidates. Using this assay as an initial filter, and adapting other assays to a high throughput format, we identify several novel chemical compounds that exhibit markedly improved anti-cryptosporidial activity and excellent selectivity

    Net primary productivity estimates and environmental variables in the Arctic Ocean: An assessment of coupled physical-biogeochemical models

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    The relative skill of 21 regional and global biogeochemical models was assessed in terms of how well the models reproduced observed net primary productivity (NPP) and environmental variables such as nitrate concentration (NO3), mixed layer depth (MLD), euphotic layer depth (Zeu), and sea ice concentration, by comparing results against a newly updated, quality-controlled in situ NPP database for the Arctic Ocean (1959-2011). The models broadly captured the spatial features of integrated NPP (iNPP) on a pan-Arctic scale. Most models underestimated iNPP by varying degrees in spite of overestimating surface NO3, MLD, and Zeu throughout the regions. Among the models, iNPP exhibited little difference over sea ice condition (ice-free vs. ice-influenced) and bottom depth (shelf vs. deep ocean). The models performed relatively well for the most recent decade and towards the end of Arctic summer. In the Barents and Greenland Seas, regional model skill of surface NO3 was best associated with how well MLD was reproduced. . Regionally, iNPP was relatively well simulated in the Beaufort Sea and the central Arctic Basin, where in situ NPP is low and nutrients are mostly depleted. Models performed less well at simulating iNPP in the Greenland and Chukchi Seas, despite the higher model skill in MLD and sea ice concentration, respectively. iNPP model skill was constrained by different factors in different Arctic Ocean regions. Our study suggests that better parameterization of biological and ecological microbial rates (phytoplankton growth and zooplankton grazing) are needed for improved Arctic Ocean biogeochemical modeling

    The Cryptosporidium parvum Kinome

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    <p>Abstract</p> <p>Background</p> <p>Hundreds of millions of people are infected with cryptosporidiosis annually, with immunocompromised individuals suffering debilitating symptoms and children in socioeconomically challenged regions at risk of repeated infections. There is currently no effective drug available. In order to facilitate the pursuit of anti-cryptosporidiosis targets and compounds, our study spans the classification of the <it>Cryptosporidium parvum </it>kinome and the structural and biochemical characterization of representatives from the CDPK family and a MAP kinase.</p> <p>Results</p> <p>The <it>C</it>. <it>parvum </it>kinome comprises over 70 members, some of which may be promising drug targets. These <it>C. parvum </it>protein kinases include members in the AGC, Atypical, CaMK, CK1, CMGC, and TKL groups; however, almost 35% could only be classified as OPK (other protein kinases). In addition, about 25% of the kinases identified did not have any known orthologues outside of <it>Cryptosporidium spp</it>. Comparison of specific kinases with their <it>Plasmodium falciparum </it>and <it>Toxoplasma gondii </it>orthologues revealed some distinct characteristics within the <it>C. parvum </it>kinome, including potential targets and opportunities for drug design. Structural and biochemical analysis of 4 representatives of the CaMK group and a MAP kinase confirms features that may be exploited in inhibitor design. Indeed, screening <it>Cp</it>CDPK1 against a library of kinase inhibitors yielded a set of the pyrazolopyrimidine derivatives (PP1-derivatives) with IC<sub>50 </sub>values of < 10 nM. The binding of a PP1-derivative is further described by an inhibitor-bound crystal structure of <it>Cp</it>CDPK1. In addition, structural analysis of <it>Cp</it>CDPK4 identified an unprecedented Zn-finger within the CDPK kinase domain that may have implications for its regulation.</p> <p>Conclusions</p> <p>Identification and comparison of the <it>C. parvum </it>protein kinases against other parasitic kinases shows how orthologue- and family-based research can be used to facilitate characterization of promising drug targets and the search for new drugs.</p

    Principales voies d'exportation de la matière organique depuis la zone euphotique, dans le secteur canadien de la mer de Beaufort, à l'été 2008

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    RÉSUMÉ: L'exceptionnel déclin de l'étendue de glace de mer observé en 2007-2008, l'augmentation du débit des rivières arctiques, de la fréquence et de l'intensité des tempêtes, le réchauffement des eaux de surface et la fonte du pergélisol sont des indices du réchauffement global dans l'océan Arctique. Ces changements soulignent la nécessité d'approfondir notre compréhension du cycle du carbone biogénique et des voies de transfert de la matière et de l'énergie sur les plateaux arctiques et d'étudier leurs impacts sur le fonctionnement de l'écosystème marin arctique. L'objectif central de ce travail était d'étudier les principales voies d'exportation de la matière organique depuis la zone euphotique dans le secteur canadien de la mer de Beaufort durant l'été 2008. Les objectifs spécifiques étaient : (1) de caractériser les patrons spatiaux et temporels de l'amplitude et de la composition de la matière organique particulaire exportée depuis la zone euphotique et d'évaluer les récents changements par rapport aux observations passées dans cette même zone, et (2) d'identifier les sources de la matière organique en sédimentation (allochtone vs autochtone) dans la zone d'étude. Pour ce faire, la production phytoplanctonique des cellules de grande (2: 5 !-lm) et de petite (0,7-5 !-lm) taille a été mesurée à sept profondeurs dans la zone euphotique au moyen du traceur isotopique 14c. Les flux verticaux du matériel particulaire ont été déterminés à l'aide de pièges à particules dérivants, déployés sous la zone euphotique à 100 m de profondeur, en moyenne pendant 18 ± 8 h. Au cours de cette étude, la production primaire était exceptionnellement élevée et dominée par des cellules de grande taille (> 5 !-lm). Cette forte production serait attribuable au retrait précoce de la glace de mer combiné à des évènements d'upwellings côtiers qui ont enrichi les eaux de surface en nutriments. Cependant, à l'exception d'une station située au nord du cap Bathurst, les flux verticaux de carbone organique par ticulaire (COP) sont demeurés faibles par rapport aux autres plateaux arctiques. Malgré une contribution élevée des substances exopolymériques (EPS) aux flux de COP, les EPS ne semblent pas avoir favorisé l'export des particules vers le benthos. L'utilisation des signatures isotopiques (8 13 C et 815N) et des ratios carbone:azote afin d'identifier les sources du matériel en sédimentation n'a été fructueuse qu'à deux stations caractérisées par une forte signature marine ou terrestre. Nos données suggèrent qu'en moyenne 81 ± 47% de la production primaire journalière a été recyclée avant d'atteindre 100 m de profondeur et, par conséquent, qu'une faible fraction de la production primaire a été exportée vers le benthos. Les résultats de notre étude mettent en évidence le rôle prépondérant des processus de recyclage, à travers le broutage du mésozooplancton (<< top-down control», en anglais) et le réseau microbien, sur le devenir de la production primaire dans le secteur canadien de la mer de Beaufort à l'été 2008. -- ABSTRACT: The exceptional decline in the sea ice extent observed in 2007-2008, the inerease Arctic river discharge, the increase in frequency and intensity of storms, the sea surface warming and the thawing of permafrost are all evidences of global warming in Arctic Ocean. These changes stress the need to further our understanding of biogenic carbon cycling and energy transfer pathways on Arctic shelves and to study the impact of the recent intensification of environmental changes taking place in the Arctic. The overall objective of this study was to investigate the main pathways of sinking export of organic material from the euphotic zone in the Canadian Beaufort Sea, in summer 2008. Specific objectives were to: (l ) characterize spatial and temporal patterns in the magnitude and composition of particulate organic material exported from the euphotic zone and evaluate recent changes with respect to previous observations in the same area, and (2) identify sources of the sinking organic material (allochthonous vs autochthonous) in the study area. Primary production rates of large (> 5 /lm) and small (0.7-5 /lm) cells were measured at seven optical depths using the 14C-ass imilation method and the sinking export of organic material was measured using short-term free-drifting particle interceptor traps deployed below the euphotic zone at 100 m, during on mean 18 ± 8 h. The combined influence of early ice retrieval and coastal upwelling supplying the surface layer in nutrients contributed to exceptionally high primary production, dominated by large cells (> 5 /lm) in summer 2008. However, except for one station located north of Cape Bathurst, the sinking export of particulate organic carbon (POC) was low compared to other Arctic shelves. Exopolymeric substances were abundant in the sinking material but did not appear to accelerate POC sinking export to the benthos. The use of isotopic signatures (8 13C, 815N) and carbon:nitrogen ratios to identify sources of the sinking material was successful only at two stations with a strong marine or terrestrial signature. Bulk estimates indicate that 81 ± 47% of the primary production in the euphotic zone was recycled in the upper 100 m, and that only a small fraction of primary production was exported to the benthos. This points to a strong influence of recycling processes throughout mesozooplankton grazing (top-down control) and microbial food web in shaping the sinking export and transfer of organic material within the marine food web of the Canadian Beaufort Sea in summer 2008
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