Tryptophan 207 is Crucial to the Unique Properties of the Human Voltage-gated Proton Channel, hHV1

Part of the “signature sequence” that defines the voltage-gated proton channel (HV1) is a tryptophan residue adjacent to the second Arg in the S4 transmembrane helix: RxWRxxR, which is perfectly conserved in all high confidence HV1 genes. Replacing Trp207 in human HV1 (hHV1) with Ala, Ser, or Phe facilitated gating, accelerating channel opening by 100-fold, and closing by 30-fold. Mutant channels opened at more negative voltages than wild-type (WT) channels, indicating that in WT channels, Trp favors a closed state. The Arrhenius activation energy, Ea, for channel opening decreased to 22 kcal/mol from 30–38 kcal/mol for WT, confirming that Trp207 establishes the major energy barrier between closed and open hHV1. Cation–π interaction between Trp207 and Arg211 evidently latches the channel closed. Trp207 mutants lost proton selectivity at pHo \u3e8.0. Finally, gating that depends on the transmembrane pH gradient (ΔpH-dependent gating), a universal feature of HV1 that is essential to its biological functions, was compromised. In the WT hHV1, ΔpH-dependent gating is shown to saturate above pHi or pHo 8, consistent with a single pH sensor with alternating access to internal and external solutions. However, saturation occurred independently of ΔpH, indicating the existence of distinct internal and external pH sensors. In Trp207 mutants, ΔpH-dependent gating saturated at lower pHo but not at lower pHi. That Trp207 mutation selectively alters pHo sensing further supports the existence of distinct internal and external pH sensors. Analogous mutations in HV1 from the unicellular species Karlodinium veneficum and Emiliania huxleyi produced generally similar consequences. Saturation of ΔpH-dependent gating occurred at the same pHo and pHi in HV1 of all three species, suggesting that the same or similar group(s) is involved in pH sensing. Therefore, Trp enables four characteristic properties: slow channel opening, highly temperature-dependent gating kinetics, proton selectivity, and ΔpH-dependent gating

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

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

Model-Driven Methodology for Rapid Deployment of Smart Spaces based on Resource-Oriented Architectures

Advances in electronics nowadays facilitate the design of smart spaces based on physical mash-ups of sensor and actuator devices. At the same time, software paradigms such as Internet of Things (IoT) and Web of Things (WoT) are motivating the creation of technology to support the development and deployment of web-enabled embedded sensor and actuator devices with two major objectives: (i) to integrate sensing and actuating functionalities into everyday objects, and (ii) to easily allow a diversity of devices to plug into the Internet. Currently, developers who are applying this Internet-oriented approach need to have solid understanding about specific platforms and web technologies. In order to alleviate this development process, this research proposes a Resource-Oriented and Ontology-Driven Development (ROOD) methodology based on the Model Driven Architecture (MDA). This methodology aims at enabling the development of smart spaces through a set of modeling tools and semantic technologies that support the definition of the smart space and the automatic generation of code at hardware level. ROOD feasibility is demonstrated by building an adaptive health monitoring service for a Smart Gym

Connecting solar flare hard X-ray spectra to in situ electron spectra A comparison of RHESSI and STEREO/SEPT observations

Aims. We aim to constrain the acceleration, injection, and transport processes of flare-accelerated energetic electrons by comparing their characteristics at the Sun with those injected into interplanetary space.Methods. We have identified 17 energetic electron events well-observed with the SEPT instrument aboard STEREO which show a clear association with a hard X-ray (HXR) flare observed with the RHESSI spacecraft. We compare the spectral indices of the RHESSI HXR spectra with those of the interplanetary electrons. Because of the frequent double-power-law shape of the in situ electron spectra, we paid special attention to the choice of the spectral index used for comparison.Results. The time difference between the electron onsets and the associated type III and microwave bursts suggests that the electron events are detected at 1 AU with apparent delays ranging from 9 to 41 min. While the parent solar activity is clearly impulsive, also showing a high correlation with extreme ultraviolet jets, most of the studied events occur in temporal coincidence with coronal mass ejections (CMEs). In spite of the observed onset delays and presence of CMEs in the low corona, we find a significant correlation of about 0.8 between the spectral indices of the HXR flare and the in situ electrons. The correlations increase if only events with significant anisotropy are considered. This suggests that transport effects can alter the injected spectra leading to a strongly reduced imprint of the flare acceleration.Conclusions. We conclude that interplanetary transport effects must be taken into account when inferring the initial acceleration of solar energetic electron events. Although our results suggest a clear imprint of flare acceleration for the analyzed event sample, a secondary acceleration might be present which could account for the observed delays. However, the limited and variable pitch-angle coverage of SEPT could also be the reason for the observed delays

Land cover, land use and malaria in the Amazon: a systematic literature review of studies using remotely sensed data

The nine countries sharing the Amazon forest accounted for 89% of all malaria cases reported in the Americas in 2008. Remote sensing can help identify the environmental determinants of malaria transmission and their temporo-spatial evolution. Seventeen studies characterizing land cover or land use features, and relating them to malaria in the Amazon subregion, were identified. These were reviewed in order to improve the understanding of the land cover/use class roles in malaria transmission. The indicators affecting the transmission risk were summarized in terms of temporal components, landscape fragmentation and anthropic pressure. This review helps to define a framework for future studies aiming to characterize and monitor malaria

In situ Laser Induced Breakdown Spectroscopy as a tool to discriminate volcanic rocks and magmatic series, Iceland

This study evaluates the potentialities of a lab-made pLIBS (portable Laser-Induced Breakdown Spectroscopy) to sort volcanic rocks belonging to various magmatic series. An in-situ chemical analysis of 19 atomic lines, including Al, Ba, Ca, Cr, Cu, Fe, Mg, Mn, Na, Si, Sr and Ti, from 21 sampled rocks was performed during a field exploration in Iceland. Iceland was chosen both for the various typologies of volcanic rocks and the rugged conditions in the field in order to test the sturdiness of the pLIPS. Elemental compositions were also measured using laboratory ICP-AES measurements on the same samples. Based on these latter results, which can be used to identify three different groups of volcanic rocks, a classification model was built in order to sort pLIBS data and to categorize unknown samples. Using a reliable statistical scheme applied to LIBS compositional data, the classification capability of the pLIBS system is clearly demonstrated (90-100% success rate). Although this prototype does not provide quantitative measurements, its use should be of particular interest for future geological field investigations

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

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