233 research outputs found

    DNA Barcoding Identifies Unknown Females and Larvae of Fannia R.-D. (Diptera: Fanniidae) from Carrion Succession Experiment and Case Report.

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    Application of available keys to European Fanniidae did not facilitate unequivocal species identification for third instar larvae and females of Fannia Robineau-Desvoidy, 1830 collected during a study of arthropod succession on pig carrion. To link these samples to known species, we took the advantage of molecular identification methods and compared newly obtained cytochrome oxidase subunit I (COI) barcode sequences against sequences deposited in reference databases. As an outcome of the results obtained, we describe for the first time a third instar larva of Fannia nigra Malloch, 1910 and Fannia pallitibia (Rondani, 1866) and a female of Fannia collini d'Assis-Fonseca, 1966. We provide combinations of characters allowing for discrimination of described insects from other Fanniidae. We provide an update for the key by Rozkošný et al. 1997, which allows differentiation between females of F. collini and other species of Fanniidae. Additionally, we provide a case of a human cadaver discovered in Southern Poland and insect fauna associated with it as the first report of F. nigra larvae developing on a human body

    Understanding the power of the prime minister : structure and agency in models of prime ministerial power

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    Understanding the power of the prime minister is important because of the centrality of the prime minister within the core executive of British government, but existing models of prime ministerial power are unsatisfactory for various reasons. This article makes an original contribution by providing an overview and critique of the dominant models of prime ministerial power, highlighting their largely positivist bent and the related problem of the prevalence of overly parsimonious conceptions of the structural contexts prime ministers face. The central argument the paper makes is that much of the existing literature on prime ministerial power is premised on flawed understandings of the relationship between structure and agency, that this leads to misunderstandings of the real scope of prime ministerial agency, as well as its determinants, and that this can be rectified by adopting a strategic-relational view of structure and agency

    Processive Movement by a Kinesin Heterodimer with an Inactivating Mutation in One Head†

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    ABSTRACT: A single molecule of the motor enzyme kinesin-1 keeps a tight grip on its microtubule track, making tens or hundreds of discrete, unidirectional 8 nm steps before dissociating. This high duty ratio processive movement is thought to require a mechanism in which alternating stepping of the two head domains of the kinesin dimer is driven by alternating, overlapped cycles of ATP hydrolysis by the two heads. The R210K point mutation in Drosophila kinesin heavy chain was reported to disrupt the ability of the enzyme active site to catalyze ATP P-O bond cleavage. We expressed R210K homodimers as well as isolated R210K heads and confirmed that both are essentially inactive. We then coexpressed tagged R210K subunits with untagged wild-type subunits and affinity purified R210K/wild-type heterodimers together with the inactive R210K homodimers. In contrast to the R210K head or homodimer, the heterodimer was a highly active (>50 % of wild-type) microtubule-stimulated ATPase, and the heterodimer displayed high duty ratio processive movement in single-molecule motility experiments. Thus, dimerization of a subunit containing the inactivating mutation with a functional subunit can complement the mutation; this must occur either by lowering or by bypassing kinetic barriers in the ATPase or mechanical cycles of the mutant head. The observations provide support for kinesin-1 gating mechanisms in which one head stimulates the rate of essential processes in the other

    Assessing the authority of political office-holders: the leadership capital index

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    This article argues that the extent to which political office-holders can effectively attain and wield authority is a function of the stock of ‘leadership capital.’ Drawing on the concept of political capital, we define leadership capital as aggregate authority composed of three dimensions: skills; relations; and reputation of a leader. Leadership capital ebbs and flows over time within a trajectory of acquisition, expenditure and inevitable depreciation. We present a Leadership Capital Index (LCI) that systematically maps out the three broad areas combining concrete measures with interpretive aspects. This can be used as a tool for systematically tracking and comparing the political fortunes of leaders in a way that is both more nuanced and robust than exclusive reliance on the latest approval ratings. We offer an illustrative case study of Tony Blair demonstrating the LCI. We conclude by discerning several promising paths for future development of the LCI

    The evolutionary roots of creativity: mechanisms and motivations

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    Funding: MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland). MASTS is funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions.We consider the evolution of cognition and the emergence of creative behaviour, in relation to vocal communication. We address two key questions: (i) what cognitive and/or social mechanisms have evolved that afford aspects of creativity?; (ii) has natural and/or sexual selection favoured human behaviours considered ‘creative’? This entails analysis of ‘creativity’, an imprecise construct: comparable properties in non-humans differ in magnitude and teleology from generally agreed human creativity. We then address two apparent problems: (i) the difference between merely novel productions and ‘creative’ ones; (ii) the emergence of creative behaviour in spite of high cost: does it fit the idea that females choose a male who succeeds in spite of a handicap (costly ornament); or that creative males capable of producing a large and complex song repertoire grew up under favourable conditions; or a demonstration of generally beneficial heightened reasoning capacity; or an opportunity to continually reinforce social bonding through changing communication tropes; or something else? We illustrate and support our argument by reference to whale and bird song; these independently evolved biological signal mechanisms objectively share surface properties with human behaviours generally called ‘creative’. Studying them may elucidate mechanisms underlying human creativity; we outline a research programme to do so.PostprintPeer reviewe

    Fused eco29kIR- and M genes coding for a fully functional hybrid polypeptide as a model of molecular evolution of restriction-modification systems

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    <p>Abstract</p> <p>Background</p> <p>The discovery of restriction endonucleases and modification DNA methyltransferases, key instruments of genetic engineering, opened a new era of molecular biology through development of the recombinant DNA technology. Today, the number of potential proteins assigned to type II restriction enzymes alone is beyond 6000, which probably reflects the high diversity of evolutionary pathways. Here we present experimental evidence that a new type IIC restriction and modification enzymes carrying both activities in a single polypeptide could result from fusion of the appropriate genes from preexisting bipartite restriction-modification systems.</p> <p>Results</p> <p>Fusion of <it>eco29kIR </it>and <it>M </it>ORFs gave a novel gene encoding for a fully functional hybrid polypeptide that carried both restriction endonuclease and DNA methyltransferase activities. It has been placed into a subclass of type II restriction and modification enzymes - type IIC. Its MTase activity, 80% that of the M.Eco29kI enzyme, remained almost unchanged, while its REase activity decreased by three times, concurrently with changed reaction optima, which presumably can be caused by increased steric hindrance in interaction with the substrate. <it>In vitro </it>the enzyme preferentially cuts DNA, with only a low level of DNA modification detected. <it>In vivo </it>new RMS can provide a 10<sup>2</sup>-fold less protection of host cells against phage invasion.</p> <p>Conclusions</p> <p>We propose a molecular mechanism of appearing of type IIC restriction-modification and M.SsoII-related enzymes, as well as other multifunctional proteins. As shown, gene fusion could play an important role in evolution of restriction-modification systems and be responsible for the enzyme subclass interconversion. Based on the proposed approach, hundreds of new type IIC enzymes can be generated using head-to-tail oriented type I, II, and III restriction and modification genes. These bifunctional polypeptides can serve a basis for enzymes with altered recognition specificities. Lastly, this study demonstrates that protein fusion may change biochemical properties of the involved enzymes, thus giving a starting point for their further evolutionary divergence.</p

    The Trump foreign policy record and the concept of transformational change

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    While there has been debate about the extent to which US foreign policy has been transformed since President Trumpfirst took office in 2017, the concept of transformational policy change has not been defined with any degree of precision. The purpose of this article is, primarily, to establish such a definition. It does this by drawing upon a number of the literatures that address domestic policy processes, in particular the work of Karl Polanyi, to suggest that transformational change rests upon paradigmatic shifts, the reconfiguration of interests, large scale institutional re-ordering and changed logics. Application of the definition to the Trump foreign policy leads us to conclude that while the Trump foreign policy owes much to the militant internationalism of the Bush years its understanding of nations and“globalism”and abandonment of a defining moral purpose represent, although incipient, partial and variegated, the beginnings of transformational change

    The N-Terminal DH-PH Domain of Trio Induces Cell Spreading and Migration by Regulating Lamellipodia Dynamics in a Rac1-Dependent Fashion

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    The guanine-nucleotide exchange factor Trio encodes two DH-PH domains that catalyze nucleotide exchange on Rac1, RhoG and RhoA. The N-terminal DH-PH domain is known to activate Rac1 and RhoG, whereas the C-terminal DH-PH domain can activate RhoA. The current study shows that the N-terminal DH-PH domain, upon expression in HeLa cells, activates Rac1 and RhoG independently from each other. In addition, we show that the flanking SH3 domain binds to the proline-rich region of the C-terminus of Rac1, but not of RhoG. However, this SH3 domain is not required for Rac1 or RhoG GDP-GTP exchange. Rescue experiments in Trio-shRNA-expressing cells showed that the N-terminal DH-PH domain of Trio, but not the C-terminal DH-PH domain, restored fibronectin-mediated cell spreading and migration defects that are observed in Trio-silenced cells. Kymograph analysis revealed that the N-terminal DH-PH domain, independent of its SH3 domain, controls the dynamics of lamellipodia. Using siRNA against Rac1 or RhoG, we found that Trio-D1-induced lamellipodia formation required Rac1 but not RhoG expression. Together, we conclude that the GEF Trio is responsible for lamellipodia formation through its N-terminal DH-PH domain in a Rac1-dependent manner during fibronectin-mediated spreading and migration

    A Scoping Review of Home Produced Heroin and Amphetamine Type Stimulant Substitutes: Implications for Prevention, Treatment and Policy

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    Several home-produced substances such as krokodil and boltushka are prevalent in many Eastern European countries. Anecdotal reports of its use have been circulating in Germany and Norway; however, this has not been confirmed. Its use has also been reported by the media in the USA, although only one confirmed report of its use exists. Home-produced drugs are associated with high levels of morbidity and a number of complex health issues such as the spread of blood borne viruses, gangrene, and internal organ damage. The high incidence of HIV rates amongst people who inject home-produced substances is a public health concern. The resulting physical health consequences of injecting these crude substances are very severe in comparison to heroin or amphetamine acquired in black markets. Due to this fact and the increased mortality associated with these substances, professionals in the area of prevention, treatment, and policy development need to be cognisant of the presentation, harms, and the dangers associated with home-produced substances globally. This scoping review aimed to examine existing literature on the subject of home-produced heroin and amphetamine-type stimulant substitutes. The review discussed the many implications such research may have in the areas of policy and practice. Data were gathered through the use of qualitative secondary resources such as journal articles, reports, reviews, case studies, and media reports. The home production of these substances relies on the utilisation of precursor drugs such as less potent stimulants, tranquillizers, analgesics, and sedatives or natural plant ingredients. The Internet underpins the facilitation of this practice as recipes, and diverted pharmaceutical sales are available widely online, and currently, ease of access to the Internet is evident worldwide. This review highlights the necessity of prevention, education, and also harm reduction related to home-produced drugs and also recommends consistent monitoring of online drug fora, online drug marketplaces, and unregulated pharmacies

    Real-world study of children and young adults with myeloproliferative neoplasms: identifying risks and unmet needs

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    Myeloproliferative neoplasms (MPNs) are uncommon in children/young adults. Here, we present data on unselected patients diagnosed before 25 years of age included from 38 centers in 15 countries. Sequential patients were included. We identified 444 patients, with median follow-up 9.7 years (0-47.8). Forty-nine (11.1%) had a history of thrombosis at diagnosis, 49 new thrombotic events were recorded (1.16% patient per year [pt/y]), perihepatic vein thromboses were most frequent (47.6% venous events), and logistic regression identified JAK2V617F mutation (P = .016) and hyperviscosity symptoms (visual disturbances, dizziness, vertigo, headache) as risk factors (P = .040). New hemorrhagic events occurred in 44 patients (9.9%, 1.04% pt/y). Disease transformation occurred in 48 patients (10.9%, 1.13% pt/y), usually to myelofibrosis (7.5%) with splenomegaly as a novel risk factor for transformation in essential thrombocythemia (ET) (P= .000) in logistical regression. Eight deaths (1.8%) were recorded, 3 after allogeneic stem cell transplantation. Concerning conventional risk scores: International Prognostic Score for Essential Thrombocythemia-Thrombosis and new International Prognostic Score for Essential Thrombocythemia-Thrombosis differentiated ET patients in terms of thrombotic risk. Both scores identified high-risk patients with the same median thrombosis-free survival of 28.5 years. No contemporary scores were able to predict survival for young ET or polycythemia vera patients. Our data represents the largest real-world study of MPN patients age < 25 years at diagnosis. Rates of thrombotic events and transformation were higher than expected compared with the previous literature. Our study provides new and reliable information as a basis for prospective studies, trials, and development of harmonized international guidelines for the specific management of young patients with MPN
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