108 research outputs found
Messer vento e madonna pioggia
Contiene Il cavalier Gelsomino e la principessa Fiordispina, comedia in tre atti per Burattini scrita da madonna Pioggia ( teatro para marionetas)Signatura : 1-8(8)Procedencia: Biblioteca del Real Colegio de Cirugía de la Armada de Cádiz, 1748-1833Fondo antiguo ilustradoEncuadernada con La cucinera domestica, Le rivoluzioni celesti, Il vero mezzo per vincere alléstrazioni delottiGrab. en contraportada de Salvion
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
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 photons s cm keV and
photons s cm keV 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 6.5 minutes of FOXSI-3
data, we constrained the quiet Sun emission in HXRs. We found upper
limits in the order of photons s cm
keV 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 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
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
Frequency and distribution of mixed Plasmodium falciparum-vivax infections in French Guiana between 2000 and 2008
Filière « Territoires, espaces, sociétés »
Participants : Isabelle Backouche, Juan Carlos Garavaglia, Nancy L. Green, Alexandra Laclau, Christian Lamouroux, Michèle de La Pradelle, Susanna Magri, Marie-Claude Maurel, Alain Musset, Daniel Nordman, Marie-Vic Ozouf-Marignier, Jacques Poloni-Simard, Paul-André Rosental, Annie Sevin, Annick Tanter-Toubon, Christian Topalov, Caroline Varlet, Nicolas Verdier, Françoise Vergneault-Belmont, François Weil, Pierre-Paul Zalio L’enseignement de la filière s’inscrit dans le cadre du séminaire bimen..
Filière « Territoires, espaces, sociétés »
Participants : Isabelle Backouche, Juan Carlos Garavaglia, Nancy L. Green, Alexandra Laclau, Christian Lamouroux, Michèle de La Pradelle, Susanna Magri, Marie-Claude Maurel, Alain Musset, Daniel Nordman, Marie-Vic Ozouf-Marignier, Jacques Poloni-Simard, Paul-André Rosental, Annie Sevin, Annick Tanter-Toubon, Christian Topalov, Caroline Varlet, Nicolas Verdier, Françoise Vergneault-Belmont, François Weil, Pierre-Paul Zalio L’enseignement de la filière s’inscrit dans le cadre du séminaire bimen..
New World Civitas, Contested Jurisdictions and Intercultural Conversation in the Construction of the Spanish Monarchy
Jurisdictional frontiers were created, contested, and negotiated among a wide range of actors, including native Americans and Europeans, with reference to the cities founded in Castilla del Oro (roughly present-day Panama). This research deals, first, with the reshaping of the concept of a city in the New World, based on its inhabitants' sense of civitas. It analyses, secondly, the creation and redefinition of jurisdiction during political conflicts and, third, the construction and maintenance of jurisdiction through local relations with indigenous populations described as "conversation". The analysis of the creation and preservation of local jurisdictions allows for an interpretation of the complexities involved in the configuration of political power and political space from below in the territories claimed by the Spanish Monarchy.Art Empir
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