2,483 research outputs found

    Resurrection of the ancestral RH5 invasion ligand provides a molecular explanation for the origin of P. falciparum malaria in humans.

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    Many important infectious diseases are the result of zoonoses, in which pathogens that normally infect animals acquire mutations that enable the breaching of species barriers to permit the infection of humans. Our understanding of the molecular events that enable host switching are often limited, and yet this is a fundamentally important question. Plasmodium falciparum, the etiological agent of severe human malaria, evolved following a zoonotic transfer of parasites from gorillas. One gene-rh5-which encodes an essential ligand for the invasion of host erythrocytes, is suspected to have played a critical role in this host switch. Genome comparisons revealed an introgressed sequence in the ancestor of P. falciparum containing rh5, which likely allowed the ancestral parasites to infect both gorilla and human erythrocytes. To test this hypothesis, we resurrected the ancestral introgressed reticulocyte-binding protein homologue 5 (RH5) sequence and used quantitative protein interaction assays to demonstrate that this ancestral protein could bind the basigin receptor from both humans and gorillas. We also showed that this promiscuous receptor binding phenotype of RH5 was shared with the parasite clade that transferred its genome segment to the ancestor of P. falciparum, while the other lineages exhibit host-specific receptor binding, confirming the central importance of this introgression event for Plasmodium host switching. Finally, since its transfer to humans, P. falciparum, and also the RH5 ligand, have evolved a strong human specificity. We show that this subsequent restriction to humans can be attributed to a single amino acid mutation in the RH5 sequence. Our findings reveal a molecular pathway for the origin and evolution of human P. falciparum malaria and may inform molecular surveillance to predict future zoonoses

    Leader autonomy support in the workplace: A meta-analytic review

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    Leader autonomy support (LAS) refers to a cluster of supervisory behaviors that are theorized to facilitate self-determined motivation in employees, potentially enabling well-being and performance. We report the results of a meta-analysis of perceived LAS in work settings, drawing from a database of 754 correlations across 72 studies (83 unique samples, N = 32,870). Results showed LAS correlated strongly and positively with autonomous work motivation, and was unrelated to controlled work motivation. Correlations became increasingly positive with the more internalized forms of work motivation described by self-determination theory. LAS was positively associated with basic needs, well-being, and positive work behaviors, and was negatively associated with distress. Correlations were not moderated by the source of LAS, country of the sample, publication status, or the operationalization of autonomy support. In addition, a meta-analytic path analysis supported motivational processes that underlie LAS and its consequences in workplaces. Overall, our findings lend support for autonomy support as a leadership approach that is consistent with self-determination and optimal functioning in work settings

    Mesoscopic Interference for Metric and Curvature (MIMAC) & Gravitational Wave Detection

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    A compact detector for space-time metric and curvature is highly desirable. Here we show that quantum spatial superpositions of mesoscopic objects, of the type which would in principle become possible with a combination of state of the art techniques and taking into account the known sources of decoherence, could be exploited to create such a detector. By using Stern-Gerlach (SG) interferometry with masses much larger than atoms, where the interferometric signal is extracted by measuring spins, we show that accelerations as low as 5×10−15ms−2Hz−1/25\times10^{-15}\textrm{ms}^{-2}\textrm{Hz}^{-1/2} or better, as well as the frame dragging effects caused by the Earth, could be sensed. Constructing such an apparatus to be non-symmetric would also enable the direct detection of curvature and gravitational waves (GWs). The GW sensitivity scales differently from the stray acceleration sensitivity, a unique feature of MIMAC. We have identified mitigation mechanisms for the known sources of noise, namely Gravity Gradient Noise (GGN), uncertainty principle and electro-magnetic forces. Hence it could potentially lead to a meter sized, orientable and vibrational noise (thermal/seismic) resilient detector of mid (ground based) and low (space based) frequency GWs from massive binaries (the predicted regimes are similar to those targeted by atom interferometers and LISA).Comment: 29 pages, 3 figure

    Location of Intra- and Extracellular M. tuberculosis Populations in Lungs of Mice and Guinea Pigs during Disease Progression and after Drug Treatment

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    The lengthy treatment regimen for tuberculosis is necessary to eradicate a small sub-population of M. tuberculosis that persists in certain host locations under drug pressure. Limited information is available on persisting bacilli and their location within the lung during disease progression and after drug treatment. Here we provide a comprehensive histopathological and microscopic evaluation to elucidate the location of bacterial populations in animal models for TB drug development

    A Bound on the Energy Loss of Partons in Nuclei

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    We derive a quantum mechanical upper bound on the amount of radiative energy loss suffered by high energy quarks and gluons in nuclear matter. The bound shows that the nuclear suppression observed in quarkonium production at high xFx_F cannot be explained in terms of energy loss of the initial or final parton states. We also argue that no nuclear suppression is expected in the photoproduction of light hadrons at large xFx_F.Comment: 15 pages, 1 figure included as a Postscript file, phyzzx.te

    Direct experimental evidence for substrate adatom incorporation into a molecular overlayer

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    While the phenomenon of metal substrate adatom incorporation into molecular overlayers is generally believed to occur in several systems, the experimental evidence for this relies on the interpretation of scanning tunnelling microscopy (STM) images, which can be ambiguous and provides no quantitative structural information. We show that surface X- ray diffraction (SXRD) uniquely provides unambiguous identification of these metal adatoms. We present the results of a detailed structural study of the Au(111)-F4TCNQ system, combining surface characterisation by STM, low energy electron diffraction and soft X-ray photoelectron spectroscopy with quantitative experimental structural information from normal incidence X-ray standing waves (NIXSW) and SXRD, together with dispersion corrected density functional theory (DFT) calculations. Excellent agreement is found between the NIXSW data and the DFT calculations regarding the height and conformation of the adsorbed molecule, which has a twisted geometry rather than the previously supposed inverted bowl shape. SXRD measurements provide unequivocal evidence for the presence and location of Au adatoms, while the DFT calculations show this reconstruction to be strongly energetically favoured.Comment: 38 pages, 10 figure
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