Cholesterol dynamics are essential for the growth and development of Plasmodium falciparum within the erythrocyte

Plasmodium spp. lack de novo cholesterol synthetic pathways and can only scavenge it from their host erythrocyte. Here we report that depletion of cholesterol from the erythrocyte plasma membrane by methyl-β-cyclodextrin (MBCD) has dramatic consequences. The removal of cholesterol results in invasion defects as well as inhibition of parasite development through the intra-erythrocytic cycle. These defects could be rescued by reconstitution with cholesterol and desmosterol but not with epicholesterol. By using live microscopy of fluorescently tagged trophozoite stage parasites, we detected rapid expulsion of the parasites from erythrocyte when exposed to MBCD for just 30 mins. Strikingly, the parasites transition from being intra-erythrocytic to extracellular within 10 seconds and do so without rupturing the erythrocyte membrane. These extruded parasites were still surrounded by the parasitophorous vacuolar membrane (PVM) and remained tethered to the erythrocyte. Electron microscopy revealed that although extracellular parasites retained their PVM, it was heavily compromised. Treatment with antimalarials that disrupt cholesterol homeostasis prior to MBCD exposure prevented the extrusion of trophozoites. These results reveal importance of cholesterol during the intra-erythrocytic development of P. falciparum and the dramatic consequences resulting from tampering with cholesterol content in the infected erythrocyte. These findings suggest dynamic nature of cholesterol within the infected erythrocyte that is critical for parasite survival.

Squids use multiple escape jet patterns throughout ontogeny

ABSTRACTThroughout their lives, squids are both predators and prey for a multitude of animals, many of which are at the top of ocean food webs, making them an integral component of the trophic structure of marine ecosystems. The escape jet, which is produced by the rapid expulsion of water from the mantle cavity through a funnel, is central to a cephalopod's ability to avoid predation throughout its life. Although squid undergo morphological and behavioral changes and experience remarkably different Reynolds number regimes throughout their development, little is known about the dynamics and propulsive efficiency of escape jets throughout ontogeny. We examine the hydrodynamics and kinematics of escape jets in squid throughout ontogeny using 2D/3D velocimetry and high-speed videography. All life stages of squid produced two escape jet patterns: (1) ‘escape jet I’ characterized by short rapid pulses resulting in vortex ring formation and (2) ‘escape jet II’ characterized by long high-volume jets, often with a leading-edge vortex ring. Paralarvae exhibited higher propulsive efficiency than adult squid during escape jet ejection, and propulsive efficiency was higher for escape jet I than escape jet II in juveniles and adults. These results indicate that although squid undergo major ecological transitions and morphology changes from paralarvae to adults, all life stages demonstrate flexibility in escape jet responses and produce escape jets of surprisingly high propulsive efficiency.This article has an associated First Person interview with the first author of the paper.

Induction of Labor Using Misoprostol With or Without Mifepristone in Intrauterine Deat

Introduction: Rapid expulsion of fetus in intrauterine fetal death is usually requested without any medical grounds for it. So an efficient, safe method for induction of labor is required. The objective of this study is to determine if pre-treatment with mifepristone followed by induction of labor with misoprostol in late intrauterine fetal death is more efficacious. Methods: We conducted a randomized controlled trial in 100 patients in B.P.Koirala Institute of Health Sciences, Nepal from June 2011 to May 2013. Group A women received single oral dose of 200 mg mifepristone, followed by induction with vaginal misoprostol after 24 hours. Group B women were induced only with vaginal misoprostol. In each group, five doses of misoprostol was used four hourly. If first cycle was unsuccessful, after break of 12 hour, second course of misoprostol was started. The primary outcome was a measure of induction to delivery time and vaginal delivery within 24 hours. Secondary outcome was to measure need of oxytocin and complications. Results: Maternal age, parity and period of gestation were comparable between groups. Number of misoprostol dose needed in group A was significantly less than group B. Mann Whitney U test showed, women in group A had significantly earlier onset of labor, however total induction to delivery interval was not significant. In group A, 85.7% delivered within 24 hours of first dose of misoprostol while in group B 70% delivered within 24 hours (p=0.07). More women in Group B required oxytocin. Conclusions: Pretreatment with mifepristone before induction of labor following late intrauterine fetal death is an effective and safe regimen. It appears to shorten the duration of induction to onset of labor. Keywords: induction of labor; intrauterine fetal death; mifepristone; misoprostol.

ESOPHAGEAL MOTILITY IN TROUBLESOME BELCHING

Context Supragastric belches are the main determinants of troublesome belching symptoms. In supragastric belches, air is rapidly brought into the esophagus and is immediately followed by a rapid expulsion before it has reached the stomach. Objective To evaluate the esophageal contraction and transit after wet swallows in patients with troublesome belching. Methods Esophageal contraction and transit were evaluated in 16 patients with troublesome belching and 15 controls. They were measured at 5, 10, 15, and 20 cm from the lower esophageal sphincter (LES) by a solid state manometric and impedance catheter. Each subject swallowed five 5 mL boluses of saline. Results The amplitude, duration and area under the curve of contractions were similar in patients with troublesome belching and control subjects. The total esophageal bolus transit time was 6.2 (1.8) s in patients with troublesome belching and 6.1 (2.3) s in controls (P = 0.55). The bolus presence time was longer in controls than in patients at 5 cm from the LES [controls: 6.0 (1.1) s, patients: 4.9 (1.2) s, P = 0.04], without differences at 10, 15 and 20 cm from the LES. The bolus head advanced time was longer in patients than controls from 20 cm to 15 cm [controls: 0.1 (0.1) s, patients: 0.7(0.8)s, P = 0.01] and from 15 cm to 10 cm [controls: 0.3 (0.1) s, patients: 1.6 (2.6) s, P = 0.01] of the LES, without difference from 10 cm to 5 cm [controls: 0.7 (0.3) s, patients: 1.0 (1.1) s, P = 0.37]. There was no difference in segment transit time. Conclusion There was no difference in esophageal contractions between patients with troublesome belching and controls. The swallowed bolus went slower into the proximal and middle esophageal body in patients than in control, but cross the distal esophageal body faster in patients than in controls.

Expulsion of Dust from Young Stellar Clusters

Young stellar clusters were identified on deep near-infrared images of 6 nearby, grand-design spirals observed with HAWK-I/VLT. A 90% completeness was reached for cluster complexes with MK = −11.5m (corresponding to masses around 104 M⊙) while the linear resolution was around 40 pc. The distribution of clusters in the (H-K)–(J-H) diagrams revealed two groups of clusters. Comparing with Starburst99 model tracks, the groups could be interpreted as one old population of clusters with low extinction and one consisting of young clusters with visual extinction as high as AV = 7m. The clear separation between the two groups suggests a rapid expulsion of dust from the young clusters.Monte-Carlo models were made assuming a cluster distribution function g(Mc, τ) = Mc−a τ−γ where Mc and τ are cluster mass and age, respectively. Fitting such models to the observed NIR color distributions, it was concluded that the cluster mortality had to be significant with γ = 0.8-1.0. Further, the star formation phase of clusters has to extend over several Myr. Young clusters have high extinctions at least the first 3 Myr but then lose their reddening over a period of around 5 Myr, depending on the exact evolutionary tracks used.

Ionisation Feedback in Star and Cluster Formation Simulations

Feedback from photoionisation may dominate on parsec scales in massive star-forming regions. Such feedback may inhibit or enhance the star formation efficiency and sustain or even drive turbulence in the parent molecular cloud. Photoionisation feedback may also provide a mechanism for the rapid expulsion of gas from young clusters' potentials, often invoked as the main cause of ‘infant mortality’. There is currently no agreement, however, with regards to the efficiency of this process and how environment may affect the direction (positive or negative) in which it proceeds. The study of the photoionisation process as part of hydrodynamical simulations is key to understanding these issues, however, due to the computational demand of the problem, crude approximations for the radiation transfer are often employed.We will briefly review some of the most commonly used approximations and discuss their major drawbacks. We will then present the results of detailed tests carried out using the detailed photoionisation code mocassin and the SPH+ionisation code iVINE code, aimed at understanding the error introduced by the simplified photoionisation algorithms. This is particularly relevant as a number of new codes have recently been developed along those lines.We will finally propose a new approach that should allow to efficiently and self-consistently treat the photoionisation problem for complex radiation and density fields.

Search for an onset mechanism that operates for both CMEs and substorms

Substorms and coronal mass ejections have been cited as the most accessible examples of the explosive energy conversion phenomenon that seems to characterize one of the behavior modes of cosmic plasmas. This paper addresses the question of whether these two examples – substorms and CMEs – support or otherwise the idea that explosive energy conversion is the result of a single process operating in different places and under different conditions. As a candidate mechanism that might be common to both substorms and CMEs we use the Forbes catastrophe model for CMEs because before testing it appears to have the potential, suitably modified, to operate also for substorms. The essence of the FCM is a sudden onset of an imbalance of the forces acting on an incipient CME. The imbalance of forces causes the CME to start to rise. Beneath the rising CME conditions develop that favor the onset of magnetic reconnection which then releases the CME and assists its expulsion. Thus the signature of the FCM is a temporally ordered sequence in which there is first the appearance of force imbalance which leads to upward (or outward) motion of the CME which leads to magnetic reconnection under it which expedites rapid expulsion. We look for the FCM signature in the output of two global magnetospheric MHD simulations that produce substorm-like events. We find the ordered sequence of events as stated but with a significant difference: there is no plasmoid prior to the onset of rapid reconnection, that is, there is no counterpart to the incipient CME on which an imbalance of forces acts to initiate the action in the FCM. If this result – that rapid tailward motion precedes the rapid reconnection of substorm expansion – is ultimately verified by other studies, it suggests that a description of the cause of substorm expansion should identify the cause of the preceding rapid tailward motion, since this leads necessarily to rapid reconnection, whatever the reconnection mechanism turns out to be. Clearly then, it is important to identify the cause of the preceding tailward motion.