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Anti-PfGARP activates programmed cell death of parasites and reduces severe malaria 期刊论文
NATURE, 2020
作者:  Rauch, Jennifer N.;  Luna, Gabriel;  Guzman, Elmer;  Audouard, Morgane;  Challis, Collin;  Sibih, Youssef E.;  Leshuk, Carolina;  Hernandez, Israel;  Wegmann, Susanne;  Hyman, Bradley T.;  Gradinaru, Viviana;  Kampmann, Martin;  Kosik, Kenneth S.
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

Malaria caused by Plasmodium falciparum remains the leading single-agent cause of mortality in children(1), yet the promise of an effective vaccine has not been fulfilled. Here, using our previously described differential screening method to analyse the proteome of blood-stage P. falciparum parasites(2), we identify P. falciparum glutamic-acid-rich protein (PfGARP) as a parasite antigen that is recognized by antibodies in the plasma of children who are relatively resistant-but not those who are susceptible-to malaria caused by P. falciparum. PfGARP is a parasite antigen of 80 kDa that is expressed on the exofacial surface of erythrocytes infected by early-to-late-trophozoite-stage parasites. We demonstrate that antibodies against PfGARP kill trophozoite-infected erythrocytes in culture by inducing programmed cell death in the parasites, and that vaccinating non-human primates with PfGARP partially protects against a challenge with P. falciparum. Furthermore, our longitudinal cohort studies showed that, compared to individuals who had naturally occurring anti-PfGARP antibodies, Tanzanian children without anti-PfGARP antibodies had a 2.5-fold-higher risk of severe malaria and Kenyan adolescents and adults without these antibodies had a twofold-higher parasite density. By killing trophozoite-infected erythrocytes, PfGARP could synergize with other vaccines that target parasite invasion of hepatocytes or the invasion of and egress from erythrocytes.


Antibodies against Plasmodium falciparum glutamic-acid-rich protein (PfGARP), an antigen expressed on the surface of infected red blood cells, kill P. falciparum parasites by inducing programmed cell death and reduce the risk of severe malaria.


  
Detection of metastable electronic states by Penning trap mass spectrometry 期刊论文
NATURE, 2020, 581 (7806) : 42-+
作者:  Rauch, Jennifer N.;  Luna, Gabriel;  Guzman, Elmer;  Audouard, Morgane;  Challis, Collin;  Sibih, Youssef E.;  Leshuk, Carolina;  Hernandez, Israel;  Wegmann, Susanne;  Hyman, Bradley T.;  Gradinaru, Viviana;  Kampmann, Martin;  Kosik, Kenneth S.
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

State-of-the-art optical clocks(1) achieve precisions of 10(-18) or better using ensembles of atoms in optical lattices(2,3) or individual ions in radio-frequency traps(4,5). Promising candidates for use in atomic clocks are highly charged ions(6) (HCIs) and nuclear transitions(7), which are largely insensitive to external perturbations and reach wavelengths beyond the optical range(8) that are accessible to frequency combs(9). However, insufficiently accurate atomic structure calculations hinder the identification of suitable transitions in HCIs. Here we report the observation of a long-lived metastable electronic state in an HCI by measuring the mass difference between the ground and excited states in rhenium, providing a non-destructive, direct determination of an electronic excitation energy. The result is in agreement with advanced calculations. We use the high-precision Penning trap mass spectrometer PENTATRAP to measure the cyclotron frequency ratio of the ground state to the metastable state of the ion with a precision of 10(-11)-an improvement by a factor of ten compared with previous measurements(10,11). With a lifetime of about 130 days, the potential soft-X-ray frequency reference at 4.96 x 10(16) hertz (corresponding to a transition energy of 202 electronvolts) has a linewidth of only 5 x 10(-8) hertz and one of the highest electronic quality factors (10(24)) measured experimentally so far. The low uncertainty of our method will enable searches for further soft-X-ray clock transitions(8,12) in HCIs, which are required for precision studies of fundamental physics(6).


Penning trap mass spectrometry is used to measure the electronic transition energy from a long-lived metastable state to the ground state in highly charged rhenium ions with a precision of 10(-11).


  
Intensive farming drives long-term shifts in avian community composition 期刊论文
NATURE, 2020, 579 (7799) : 393-+
作者:  Oh, Eugene;  Mark, Kevin G.;  Mocciaro, Annamaria;  Watson, Edmond R.;  Prabu, J. Rajan;  Cha, Denny D.;  Kampmann, Martin;  Gamarra, Nathan;  Zhou, Coral Y.;  Rape, Michael
收藏  |  浏览/下载:15/0  |  提交时间:2020/05/13

Variation in vegetation and climate affects the long-term changes in bird communities in intensive-agriculture habitats, but not in diversified-agriculture or natural-forest habitats, by changing the local colonization and extinction rates.


Agricultural practices constitute both the greatest cause of biodiversity loss and the greatest opportunity for conservation(1,2), given the shrinking scope of protected areas in many regions. Recent studies have documented the high levels of biodiversity-across many taxa and biomes-that agricultural landscapes can support over the short term(1,3,4). However, little is known about the long-term effects of alternative agricultural practices on ecological communities(4,5) Here we document changes in bird communities in intensive-agriculture, diversified-agriculture and natural-forest habitats in 4 regions of Costa Rica over a period of 18 years. Long-term directional shifts in bird communities were evident in intensive- and diversified-agricultural habitats, but were strongest in intensive-agricultural habitats, where the number of endemic and International Union for Conservation of Nature (IUCN) Red List species fell over time. All major guilds, including those involved in pest control, pollination and seed dispersal, were affected. Bird communities in intensive-agricultural habitats proved more susceptible to changes in climate, with hotter and drier periods associated with greater changes in community composition in these settings. These findings demonstrate that diversified agriculture can help to alleviate the long-term loss of biodiversity outside natural protected areas(1).


  
Centrosome anchoring regulates progenitor properties and cortical formation 期刊论文
NATURE, 2020
作者:  Guo, Xiaoyan;  Aviles, Giovanni;  Liu, Yi;  Tian, Ruilin;  Unger, Bret A.;  Lin, Yu-Hsiu T.;  Wiita, Arun P.;  Xu, Ke;  Correia, M. Almira;  Kampmann, Martin
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

CEP83-mediated anchoring of the centrosome to the apical membrane in radial glial progenitor cells regulates their mechanical properties and thereby influences the size and configuration of the mammalian cortex.


Radial glial progenitor cells (RGPs) are the major neural progenitor cells that generate neurons and glia in the developing mammalian cerebral cortex(1-4). In RGPs, the centrosome is positioned away from the nucleus at the apical surface of the ventricular zone of the cerebral cortex(5-8). However, the molecular basis and precise function of this distinctive subcellular organization of the centrosome are largely unknown. Here we show in mice that anchoring of the centrosome to the apical membrane controls the mechanical properties of cortical RGPs, and consequently their mitotic behaviour and the size and formation of the cortex. The mother centriole in RGPs develops distal appendages that anchor it to the apical membrane. Selective removal of centrosomal protein 83 (CEP83) eliminates these distal appendages and disrupts the anchorage of the centrosome to the apical membrane, resulting in the disorganization of microtubules and stretching and stiffening of the apical membrane. The elimination of CEP83 also activates the mechanically sensitive yes-associated protein (YAP) and promotes the excessive proliferation of RGPs, together with a subsequent overproduction of intermediate progenitor cells, which leads to the formation of an enlarged cortex with abnormal folding. Simultaneous elimination of YAP suppresses the cortical enlargement and folding that is induced by the removal of CEP83. Together, these results indicate a previously unknown role of the centrosome in regulating the mechanical features of neural progenitor cells and the size and configuration of the mammalian cerebral cortex.