Exploring impulsive solar magnetic energy release and particle acceleration with focused hard X-ray imaging spectroscopy

How impulsive magnetic energy release leads to solar eruptions and how those eruptions are energized and evolve are vital unsolved problems in Heliophysics. The standard model for solar eruptions summarizes our current understanding of these events. Magnetic energy in the corona is released through drastic restructuring of the magnetic field via reconnection. Electrons and ions are then accelerated by poorly understood processes. Theories include contracting loops, merging magnetic islands, stochastic acceleration, and turbulence at shocks, among others. Although this basic model is well established, the fundamental physics is poorly understood. HXR observations using grazing-incidence focusing optics can now probe all of the key regions of the standard model. These include two above-the-looptop (ALT) sources which bookend the reconnection region and are likely the sites of particle acceleration and direct heating. The science achievable by a direct HXR imaging instrument can be summarized by the following science questions and objectives which are some of the most outstanding issues in solar physics (1) How are particles accelerated at the Sun? (1a) Where are electrons accelerated and on what time scales? (1b) What fraction of electrons is accelerated out of the ambient medium? (2) How does magnetic energy release on the Sun lead to flares and eruptions? A Focusing Optics X-ray Solar Imager (FOXSI) instrument, which can be built now using proven technology and at modest cost, would enable revolutionary advancements in our understanding of impulsive magnetic energy release and particle acceleration, a process which is known to occur at the Sun but also throughout the Universe

Use of Plasmodium falciparum culture-adapted field isolates for in vitro exflagellation-blocking assay

International audienceA major requirement for malaria elimination is the development of transmission-blocking interventions. In vitro transmission-blocking bioassays currently mostly rely on the use of very few Plasmodium falciparum reference laboratory strains isolated decades ago. To fill a piece of the gap between laboratory experimental models and natural systems, the purpose of this work was to determine if culture-adapted field isolates of P. falciparum are suitable for in vitro transmission-blocking bioassays targeting functional maturity of male gametocytes: exflagellation. Plasmodium falciparum isolates were adapted to in vitro culture before being used for in vitro gametocyte production. Maturation was assessed by microscopic observation of gametocyte morphology over time of culture and the functional viability of male gametocytes was assessed by microscopic counting of exflagellating gametocytes. Suitability for in vitro exflagellation-blocking bioassays was determined using dihydroartemisinin and methylene blue. In vitro gametocyte production was achieved using two isolates from French Guiana and two isolates from Cambodia. Functional maturity of male gametocytes was assessed by exflagellation observations and all four isolates could be used in exflagellation-blocking bioassays with adequate response to methylene blue and dihydroartemisinin. This work shows that in vitro culture-adapted P. falciparum field isolates of different genetic background, from South America and Southeast Asia, can successfully be used for bioassays targeting the male gametocyte to gamete transition, exflagellation

Solar Jet Hunter: a citizen science initiative to identify coronal jets in EUV data sets

Context. Solar coronal jets seen in EUV are ubiquitous on the Sun, have been found in and at the edges of active regions, at the boundaries of coronal holes, and in the quiet Sun. Jets have various shapes, sizes, brightness, velocities and duration in time, which complicates their detection by automated algorithms. So far, solar jets reported in the Heliophysics Event Knowledgebase (HEK) have been mostly reported by humans looking for them in the data, with different levels of precision regarding their timing and positions. Aims. We create a catalogue of solar jets observed in EUV at 304 {\AA} containing precise and consistent information on the jet timing, position and extent. Methods. We designed a citizen science project, "Solar Jet Hunter", on the Zooniverse platform, to analyze EUV observations at 304 {\AA} from the Solar Dynamic Observatory/Atmospheric Imaging Assembly (SDO/AIA). We created movie strips for regions of the Sun in which jets have been reported in HEK and ask the volunteers to 1) confirm the presence of at least one jet in the data and 2) report the timing, position and extent of the jet. Results. We report here the design of the project and the results obtained after the analysis of data from 2011 to 2016. 365 "coronal jet" events from HEK served as input for the citizen science project, equivalent to more than 120,000 images distributed into 9,689 "movie strips". Classification by the citizen scientists resulted with only 21% of the data containing a jet, and 883 individual jets being identified. Conclusions. We demonstrate how citizen science can enhance the analysis of solar data with the example of Solar Jet Hunter. The catalogue of jets thus created is publicly available and will enable statistical studies of jets and related phenomena. This catalogue will also be used as a training set for machines to learn to recognize jets in further data sets

Evolution of Fitness Cost-Neutral Mutant PfCRT Conferring P. falciparum 4-Aminoquinoline Drug Resistance Is Accompanied by Altered Parasite Metabolism and Digestive Vacuole Physiology

Southeast Asia is an epicenter of multidrug-resistant Plasmodium falciparum strains. Selective pressures on the subcontinent have recurrently produced several allelic variants of parasite drug resistance genes, including the P. falciparum chloroquine resistance transporter (pfcrt). Despite significant reductions in the deployment of the 4-aminoquinoline drug chloroquine (CQ), which selected for the mutant pfcrt alleles that halted CQ efficacy decades ago, the parasite pfcrt locus is continuously evolving. This is highlighted by the presence of a highly mutated allele, Cam734 pfcrt, which has acquired the singular ability to confer parasite CQ resistance without an associated fitness cost. Here, we used pfcrt-specific zinc-finger nucleases to genetically dissect this allele in the pathogenic setting of asexual blood-stage infection. Comparative analysis of drug resistance and growth profiles of recombinant parasites that express Cam734 or variants thereof, Dd2 (the most common Southeast Asian variant), or wild-type pfcrt, revealed previously unknown roles for PfCRT mutations in modulating parasite susceptibility to multiple antimalarial agents. These results were generated in the GC03 strain, used in multiple earlier pfcrt studies, and might differ in natural isolates harboring this allele. Results presented herein show that Cam734-mediated CQ resistance is dependent on the rare A144F mutation that has not been observed beyond Southeast Asia, and reveal distinct impacts of this and other Cam734-specific mutations on CQ resistance and parasite growth rates. Biochemical assays revealed a broad impact of mutant PfCRT isoforms on parasite metabolism, including nucleoside triphosphate levels, hemoglobin catabolism and disposition of heme, as well as digestive vacuole volume and pH. Results from our study provide new insights into the complex molecular basis and physiological impact of PfCRT-mediated antimalarial drug resistance, and inform ongoing efforts to characterize novel pfcrt alleles that can undermine the efficacy of first-line antimalarial drug regimens

Plasmodium chabaudi chabaudi malaria parasites can develop stable resistance to atovaquone with a mutation in the cytochrome b gene

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum</it>, has developed resistance to many of the drugs in use. The recommended treatment policy is now to use drug combinations. The atovaquone-proguanil (AP) drug combination, is one of the treatment and prophylaxis options. Atovaquone (ATQ) exerts its action by inhibiting plasmodial mitochondria electron transport at the level of the cytochrome bc1 complex. <it>Plasmodium falciparum in vitro </it>resistance to ATQ has been associated with specific point mutations in the region spanning codons 271-284 of the <it>cytochrome b </it>gene. ATQ -resistant <it>Plasmodium yoelii </it>and <it>Plasmodium berghei </it>lines have been obtained and resistant lines have amino acid mutations in their CYT <it>b </it>protein sequences. <it>Plasmodium chabaudi </it>model for studying drug-responses and drug-resistance selection is a very useful rodent malaria model but no ATQ resistant parasites have been reported so far. The aim of this study was to determine the ATQ sensitivity of the <it>P. chabaudi </it>clones, to select a resistant parasite line and to perform genotypic characterization of the <it>cytb </it>gene of these clones.</p> <p>Methods</p> <p>To select for ATQ resistance, <it>Plasmodium. chabaudi chabaudi </it>clones were exposed to gradually increasing concentrations of ATQ during several consecutive passages in mice. <it>Plasmodium chabaudi cytb </it>gene was amplified and sequenced.</p> <p>Results</p> <p>ATQ resistance was selected from the clone AS-3CQ. In order to confirm whether an heritable genetic mutation underlies the response of AS-ATQ to ATQ, the stability of the drug resistance phenotype in this clone was evaluated by measuring drug responses after (i) multiple blood passages in the absence of the drug, (ii) freeze/thawing of parasites in liquid nitrogen and (iii) transmission through a mosquito host, <it>Anopheles stephensi</it>. ATQ resistance phenotype of the drug-selected parasite clone kept unaltered. Therefore, ATQ resistance in clone AS-ATQ is genetically encoded. The Minimum Curative Dose of AS-ATQ showed a six-fold increase in MCD to ATQ relative to AS-3CQ.</p> <p>Conclusions</p> <p>A mutation was found on the <it>P. chabaudi cytb </it>gene from the AS-ATQ sample a substitution at the residue Tyr268 for an Asn, this mutation is homologous to the one found in <it>P. falciparum </it>isolates resistant to ATQ.</p

A Voltage-Gated H+ Channel Underlying pH Homeostasis in Calcifying Coccolithophores

Marine coccolithophorid phytoplankton are major producers of biogenic calcite, playing a significant role in the global carbon cycle. Predicting the impacts of ocean acidification on coccolithophore calcification has received much recent attention and requires improved knowledge of cellular calcification mechanisms. Uniquely amongst calcifying organisms, coccolithophores produce calcified scales (coccoliths) in an intracellular compartment and secrete them to the cell surface, requiring large transcellular ionic fluxes to support calcification. In particular, intracellular calcite precipitation using HCO3− as the substrate generates equimolar quantities of H+ that must be rapidly removed to prevent cytoplasmic acidification. We have used electrophysiological approaches to identify a plasma membrane voltage-gated H+ conductance in Coccolithus pelagicus ssp braarudii with remarkably similar biophysical and functional properties to those found in metazoans. We show that both C. pelagicus and Emiliania huxleyi possess homologues of metazoan Hv1 H+ channels, which function as voltage-gated H+ channels when expressed in heterologous systems. Homologues of the coccolithophore H+ channels were also identified in a diversity of eukaryotes, suggesting a wide range of cellular roles for the Hv1 class of proteins. Using single cell imaging, we demonstrate that the coccolithophore H+ conductance mediates rapid H+ efflux and plays an important role in pH homeostasis in calcifying cells. The results demonstrate a novel cellular role for voltage gated H+ channels and provide mechanistic insight into biomineralisation by establishing a direct link between pH homeostasis and calcification. As the coccolithophore H+ conductance is dependent on the trans-membrane H+ electrochemical gradient, this mechanism will be directly impacted by, and may underlie adaptation to, ocean acidification. The presence of this H+ efflux pathway suggests that there is no obligate use of H+ derived from calcification for intracellular CO2 generation. Furthermore, the presence of Hv1 class ion channels in a wide range of extant eukaryote groups indicates they evolved in an early common ancestor

Confirmation of emergence of mutations associated with atovaquone-proguanil resistance in unexposed Plasmodium falciparum isolates from Africa

BACKGROUND: In vitro and in vivo resistance of Plasmodium falciparum to atovaquone or atovaquone-proguanil hydrochloride combination has been associated to two point mutations in the parasite cytochrome b (cytb) gene (Tyr268Ser and Tyr268Asn). However, little is known about the prevalence of codon-268 mutations in natural populations of P. falciparum without previous exposure to the drug in Africa. METHODS: The prevalence of codon-268 mutations in the cytb gene of African P. falciparum isolates from Nigeria, Malawi and Senegal, where atovaquone-proguanil has not been introduced for treatment of malaria was assessed. Genotyping of the cytb gene in isolates of P. falciparum was performed by PCR-restriction fragment length polymorphism and confirmed by sequencing. RESULTS: 295 samples from Nigeria (111), Malawi (91) and Senegal (93) were successfully analyzed for detection of either mutant Tyr268Ser or Tyr268Asn. No case of Ser268 or Asn268 was detected in cytb gene of parasites from Malawi or Senegal. However, Asn268 was detected in five out of 111 (4.5%) unexposed P. falciparum isolates from Nigeria. In addition, one out of these five mutant Asn268 isolates showed an additional cytb mutation leading to a Pro266Thr substitution inside the ubiquinone reduction site. CONCLUSION: No Tyr268Ser mutation is found in cytb of P. falciparum isolates from Nigeria, Malawi or Senegal. This study reports for the first time cytb Tyr268Asn mutation in unexposed P. falciparum isolates from Nigeria. The emergence in Africa of P. falciparum isolates with cytb Tyr268Asn mutation is a matter of serious concern. Continuous monitoring of atovaquone-proguanil resistant P. falciparum in Africa is warranted for the rational use of this new antimalarial drug, especially in non-immune travelers

On the faintest solar coronal hard X-rays observed with FOXSI

Solar nanoflares are small eruptive events releasing magnetic energy in the quiet corona. If nanoflares follow the same physics as their larger counterparts, they should emit hard X-rays (HXRs) but with a rather faint intensity. A copious and continuous presence of nanoflares would deliver enormous amounts of energy into the solar corona, possibly accounting for its high temperatures. To date, there has not been any direct observation of such sustained and persistent HXRs from the quiescent Sun. However, Hannah et al. in 2010 constrained the quiet Sun HXR emission using almost 12 days of quiescent solar-off-pointing observations by RHESSI. These observations set upper limits at $3.4\times 10^{-2}$ photons$^{-1}$ s$^{-1}$ cm$^{-2}$ keV$^{-1}$ and $9.5\times 10^{-4}$ photons$^{-1}$ s$^{-1}$ cm$^{-2}$ keV$^{-1}$ for the 3-6 keV and 6-12 keV energy ranges, respectively. Observing feeble HXRs is challenging because it demands high sensitivity and dynamic range instruments in HXRs. The Focusing Optics X-ray Solar Imager (FOXSI) sounding rocket experiment excels in these two attributes. Particularly, FOXSI completed its third successful flight (FOXSI-3) on September 7th, 2018. During FOXSI-3's flight, the Sun exhibited a fairly quiet configuration, displaying only one aged non-flaring active region. Using the entire $\sim$6.5 minutes of FOXSI-3 data, we constrained the quiet Sun emission in HXRs. We found $2\sigma$ upper limits in the order of $\sim 10^{-3}$ photons$^{-1}$ s$^{-1}$ cm$^{-2}$ keV$^{-1}$ for the 5-10 keV energy range. FOXSI-3's upper limit is consistent with what was reported by Hannah et al., 2010, but FOXSI-3 achieved this result using $\sim$1/2640 less time than RHESSI. A possible future spacecraft using FOXSI's concept would allow enough observation time to constrain the current HXR quiet Sun limits further or perhaps even make direct detections

Atmospheric neutrinos with three flavor mixing

We analyze the atmospheric neutrino data in the context of three flavor neutrino oscillations taking account of the matter effects in the earth. With the hierarchy among the vacuum mass eigenvalues $\mu_3^2 \gg \mu_2^2 \geq \mu_1^2$, the solution of the atmospheric neutrino problem depends on $\delta_{31}=\mu_3^2 - \mu_1^2$ and the $13$ and $23$ mixing angles $\phi$ and $\psi$. Whereas the sub-GeV atmospheric neutrino data imposes only a lower limit on $\delta_{31} > 10^{-3} eV^2$, the zenith angle dependent suppression observed in the multi-GeV data limits $\delta_{31}$ from above also. The allowed regions of the parameter space are strongly constrained by the multi-GeV data. Combined with our earlier solution to the solar neutrino problem which depends on $\delta_{21}= \mu_2^2-\mu_1^2$ and the $12$ and $13$ mixing angles $\omega$ and $\phi$, we have obtained the ranges of values of the five neutrino parameters which solve both the solar and the atmospheric neutrino problems simultaneously.Comment: 21 pages Revtex, 7 figures as 7 ps files, Zenith angle binned multi-Gev analysis redone with the Kamiokande detector efficiencies include