Global S&T Development Trend Analysis Platform of Resources and Environment
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.
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).
