Non-physiological increase of AV conduction time in sinus disease patients programmed in AAIR-based pacing mode

Purpose The EVOCAVDS trial aimed to quantify the paradoxal atrioventricular (AV) conduction time lengthening in sinus node (SD) patients (pts) paced in AAIR-based pacing mode. Methods SD pts, implanted with dual-chamber pacemaker programmed in AAIR-based pacing mode, were randomized in two arms for a 1-month period: the low atrial pacing (LAP; basic rate at 60 bpm, dual sensor with minimal slope) and the high atrial pacing (HAP; basic rate at 70 bpm, dual sensor with optimized slope, overdrive pacing) arm. At 1 month, crossover was performed for an additional 1-month period. AV conduction time, AV block occurrence and AV conduction time adaptation during exercise were ascertained from device memories at each follow-up. Results Seventy-nine pts participated to the analysis (75 ± 8 years; 32 male; PR = 184 ± 38 ms; bundle branch block n = 12; AF history n = 36; antiarrhythmic treatment n = 53; beta-blockers n = 27; class III/Ic n = 18; both n = 8). The mean AV conduction time was significantly greater during the HAP (275 ± 51 ms) vs. LAP (263 ± 49 ms) period (p < 0.0001). Class III/Ic drugs were the only predictors of this abnormal behaviour. Degree II/III AV blocks occurred in 49 % of pts in the HAP vs. 19 % in the LAP period (p < 0.0001). Fifty-two patients (66 %) presented a lengthening of AV conduction time during exercise. Conclusion AAIR-based pacing in SD pts may induce a significant lengthening of pts’ AV conduction time, including frequent abnormal adaptation of AV conduction time during exercise

Development and Application of a Simple Plaque Assay for the Human Malaria Parasite Plasmodium falciparum.

Malaria is caused by an obligate intracellular protozoan parasite that replicates within and destroys erythrocytes. Asexual blood stages of the causative agent of the most virulent form of human malaria, Plasmodium falciparum, can be cultivated indefinitely in vitro in human erythrocytes, facilitating experimental analysis of parasite cell biology, biochemistry and genetics. However, efforts to improve understanding of the basic biology of this important pathogen and to develop urgently required new antimalarial drugs and vaccines, suffer from a paucity of basic research tools. This includes a simple means of quantifying the effects of drugs, antibodies and gene modifications on parasite fitness and replication rates. Here we describe the development and validation of an extremely simple, robust plaque assay that can be used to visualise parasite replication and resulting host erythrocyte destruction at the level of clonal parasite populations. We demonstrate applications of the plaque assay by using it for the phenotypic characterisation of two P. falciparum conditional mutants displaying reduced fitness in vitro

MethOds and tools for comprehensive impact Assessment of the CCAM solutions for passengers and goods. D1.1: CCAM solutions review and gaps

Review of the state-of-the-art on Cooperative, Connected and Automated mobility use cases, scenarios, business models, Key Performance Indicators, impact evaluation methods, technologies, and user needs (for organisations & citizens)

Limits of the seismogenic zone in the epicentral region of the 26 December 2004 great Sumatra-Andaman earthquake: Results from seismic refraction and wide-angle reflection surveys and thermal modeling

The 26 December 2004 Sumatra earthquake (Mw = 9.1) initiated around 30 km depth and ruptured 1300 km of the Indo-Australian Sunda plate boundary. During the Sumatra OBS (ocean bottom seismometer) survey, a wide angle seismic profile was acquired across the epicentral region. A seismic velocity model was obtained from combined travel time tomography and forward modeling. Together with reflection seismic data from the SeaCause II cruise, the deep structure of the source region of the great earthquake is revealed. Four to five kilometers of sediments overlie the oceanic crust at the trench, and the subducting slab can be imaged down to a depth of 35 km. We find a crystalline backstop 120 km from the trench axis, below the fore arc basin. A high velocity zone at the lower landward limit of the raycovered domain, at 22 km depth, marks a shallow continental Moho, 170 km from the trench. The deep structure obtained from the seismic data was used to construct a thermal model of the fore arc in order to predict the limits of the seismogenic zone along the plate boundary fault. Assuming 100C-150C as its updip limit, the seismogenic zone is predicted to begin 530 km from the trench. The downdip limit of the 2004 rupture as inferred from aftershocks is within the 350C 450C temperature range, but this limit is 210-250 km from the trench axis and is much deeper than the fore arc Moho. The deeper part of the rupture occurred along the contact between the mantle wedge and the downgoing plate

Calmodulin-like proteins localized to the conoid regulate motility and cell invasion by Toxoplasma gondii

Toxoplasma gondii contains an expanded number of calmodulin (CaM)-like proteins whose functions are poorly understood. Using a combination of CRISPR/Cas9-mediated gene editing and a plant-like auxin-induced degron (AID) system, we examined the roles of three apically localized CaMs. CaM1 and CaM2 were individually dispensable, but loss of both resulted in a synthetic lethal phenotype. CaM3 was refractory to deletion, suggesting it is essential. Consistent with this prediction auxin-induced degradation of CaM3 blocked growth. Phenotypic analysis revealed that all three CaMs contribute to parasite motility, invasion, and egress from host cells, and that they act downstream of microneme and rhoptry secretion. Super-resolution microscopy localized all three CaMs to the conoid where they overlap with myosin H (MyoH), a motor protein that is required for invasion. Biotinylation using BirA fusions with the CaMs labeled a number of apical proteins including MyoH and its light chain MLC7, suggesting they may interact. Consistent with this hypothesis, disruption of MyoH led to degradation of CaM3, or redistribution of CaM1 and CaM2. Collectively, our findings suggest these CaMs may interact with MyoH to control motility and cell invasion

Deep structure of the Ionian Sea and Sicily Dionysus - Cruise No. M111, October 10 - November 1, 2014, Catania (Italy) – Catania (Italy)

Summary The origin of the Ionian Sea lithosphere and the deep structure of its margins remain a little investigated part of the Mediterranean Sea. To shed light on the plate tectonic setting in this central part of southern Europe, R/V METEOR cruise M111 set out to acquire deep penetrating seismic data in the Ionian Sea. M111 formed the core of an amphibious investigation covering the Ionian Sea and island of Sicily. A total of 153 OBS/OBH deployments using French and German instruments were successfully carried out, in addition to 12 land stations installed on Sicily, which recorded the offshore air gun shots. The aim of this onshore-offshore study is to quantify the deep geometry and architecture of the Calabria subduction zone and Ionian Sea lithosphere and to shed light on the nature of the Ionian Sea crust (oceanic crust vs. thinned continental crust). Investigating the structure of the Ionian crust and lithospheric mantle will contribute to unravel the unknown ocean-continent transition and Tethys margin. Analyzing the tectonic activity and active deformation zones is essential for understanding the subduction processes that underlie the neotectonics of the Calabrian subduction zone and earthquake hazard of the Calabria/Sicily region, especially in the vicinity of local decoupling zones

Ionian Abyssal Plain: a window into the Tethys oceanic lithosphere

The nature of the Ionian Sea crust has been the subject of scientific debate for more than 30 years, mainly because seismic imaging of the deep crust and upper mantle of the Ionian Abyssal Plain (IAP) has not been conclusive to date. The IAP is sandwiched between the Calabrian and Hellenic subduction zones in the central Mediterranean. A NNE–SSW-oriented 131&thinsp;km long seismic refraction and wide-angle reflection profile, consisting of eight ocean bottom seismometers and hydrophones, was acquired in 2014. The profile was designed to univocally confirm the proposed oceanic nature of the IAP crust as a remnant of the Tethys and to confute its interpretation as a strongly thinned part of the African continental crust. A P-wave velocity model developed from travel-time forward modelling is refined by gravimetric data and synthetic modelling of the seismic data. A roughly 6–7&thinsp;km thick crust with velocities ranging from 5.1 to 7.2&thinsp;km&thinsp;s−1, top to bottom, can be traced throughout the IAP. In the vicinity of the Medina seamounts at the southern IAP boundary, the crust thickens to about 9&thinsp;km and seismic velocities decrease to 6.8&thinsp;km&thinsp;s−1 at the crust–mantle boundary. The seismic velocity distribution and depth of the crust–mantle boundary in the IAP document its oceanic nature and support the interpretation of the IAP as a remnant of the Tethys lithosphere with the Malta Escarpment as a transform margin and a Tethys opening in the NNW–SSE direction.</p

Genetic Relations Between the Aves Ridge and the Grenada Back-Arc Basin, East Caribbean Sea

The Grenada Basin separates the active Lesser Antilles Arc from the Aves Ridge, described as a Cretaceous‐Paleocene remnant of the “Great Arc of the Caribbean.” Although various tectonic models have been proposed for the opening of the Grenada Basin, the data on which they rely are insufficient to reach definitive conclusions. This study presents, a large set of deep‐penetrating multichannel seismic reflection data and dredge samples acquired during the GARANTI cruise in 2017. By combining them with published data including seismic reflection data, wide‐angle seismic data, well data and dredges, we refine the understanding of the basement structure, depositional history, tectonic deformation and vertical motions of the Grenada Basin and its margins as follows: (1) rifting occurred during the late Paleocene‐early Eocene in a NW‐SE direction and led to seafloor spreading during the middle Eocene; (2) this newly formed oceanic crust now extends across the eastern Grenada Basin between the latitude of Grenada and Martinique; (3) asymmetrical pre‐Miocene depocenters support the hypothesis that the southern Grenada Basin originally extended beneath the present‐day southern Lesser Antilles Arc and probably partly into the present‐day forearc before the late Oligocene‐Miocene rise of the Lesser Antilles Arc; and (4) the Aves Ridge has subsided along with the Grenada Basin since at least the middle Eocene, with a general subsidence slowdown or even an uplift during the late Oligocene, and a sharp acceleration on its southeastern flank during the late Miocene. Until this acceleration of subsidence, several bathymetric highs remained shallow enough to develop carbonate platforms

SAS6-like protein in Plasmodium indicates that conoid-associated apical complex proteins persist in invasive stages within the mosquito vector

The SAS6-like (SAS6L) protein, a truncated paralogue of the ubiquitous basal body/centriole protein SAS6, has been characterised recently as a flagellum protein in trypanosomatids, but associated with the conoid in apicomplexan Toxoplasma. The conoid has been suggested to derive from flagella parts, but is thought to have been lost from some apicomplexans including the malaria-causing genus Plasmodium. Presence of SAS6L in Plasmodium, therefore, suggested a possible role in flagella assembly in male gametes, the only flagellated stage. Here, we have studied the expression and role of SAS6L throughout the Plasmodium life cycle using the rodent malaria model P. berghei. Contrary to a hypothesised role in flagella, SAS6L was absent during gamete flagellum formation. Instead, SAS6L was restricted to the apical complex in ookinetes and sporozoites, the extracellular invasive stages that develop within the mosquito vector. In these stages SAS6L forms an apical ring, as we show is also the case in Toxoplasma tachyzoites. The SAS6L ring was not apparent in blood-stage invasive merozoites, indicating that the apical complex is differentiated between the different invasive forms. Overall this study indicates that a conoid-associated apical complex protein and ring structure is persistent in Plasmodium in a stage-specific manner