Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection

Antiretroviral therapy-naive HIV-1 infected infants experience poor viral containment and rapid disease progression compared to adults. Viral factors (e.g. transmitted cytotoxic T- lymphocyte (CTL) escape mutations) or infant factors (e.g. reduced CTL functional capacity) may explain this observation. We assessed CTL functionality by analysing selection in CTL-targeted HIV-1 epitopes following perinatal infection. HIV-1 gag, pol and nef sequences were generated from a historical repository of longitudinal specimens from 19 vertically infected infants. Evolutionary rate and selection were estimated for each gene and in CTL-restricted and non-restricted epitopes. Evolutionary rate was higher in nef and gag vs. pol, and lower in infants with non-severe immunosuppression vs. severe immunosuppression across gag and nef. Selection pressure was stronger in infants with non-severe immunosuppression vs. severe immunosuppression across gag. The analysis also showed that infants with non-severe immunosuppression had stronger selection in CTL-restricted vs. non-restricted epitopes in gag and nef. Evidence of stronger CTL selection was absent in infants with severe immunosuppression. These data indicate that infant CTLs can exert selection pressure on gag and nef epitopes in early infection and that stronger selection across CTL epitopes is associated with favourable clinical outcomes. These results have implications for the development of paediatric HIV-1 vaccines

αB Crystallin Is Apically Secreted within Exosomes by Polarized Human Retinal Pigment Epithelium and Provides Neuroprotection to Adjacent Cells

αB Crystallin is a chaperone protein with anti-apoptotic and anti-inflammatory functions and has been identified as a biomarker in age-related macular degeneration. The purpose of this study was to determine whether αB crystallin is secreted from retinal pigment epithelial (RPE) cells, the mechanism of this secretory pathway and to determine whether extracellular αB crystallin can be taken up by adjacent retinal cells and provide protection from oxidant stress. We used human RPE cells to establish that αB crystallin is secreted by a non-classical pathway that involves exosomes. Evidence for the release of exosomes by RPE and localization of αB crystallin within the exosomes was achieved by immunoblot, immunofluorescence, and electron microscopic analyses. Inhibition of lipid rafts or exosomes significantly reduced αB crystallin secretion, while inhibitors of classic secretory pathways had no effect. In highly polarized RPE monolayers, αB crystallin was selectively secreted towards the apical, photoreceptor-facing side. In support, confocal microscopy established that αB crystallin was localized predominantly in the apical compartment of RPE monolayers, where it co-localized in part with exosomal marker CD63. Severe oxidative stress resulted in barrier breakdown and release of αB crystallin to the basolateral side. In normal mouse retinal sections, αB crystallin was identified in the interphotoreceptor matrix. An increased uptake of exogenous αB crystallin and protection from apoptosis by inhibition of caspase 3 and PARP activation were observed in stressed RPE cultures. αB Crystallin was taken up by photoreceptors in mouse retinal explants exposed to oxidative stress. These results demonstrate an important role for αB crystallin in maintaining and facilitating a neuroprotective outer retinal environment and may also explain the accumulation of αB crystallin in extracellular sub-RPE deposits in the stressed microenvironment in age-related macular degeneration. Thus evidence from our studies supports a neuroprotective role for αB crystallin in ocular diseases

Motivational component profiles in university students learning histology: a comparative study between genders and different health science curricula

Background: The students' motivation to learn basic sciences in health science curricula is poorly understood. The purpose of this study was to investigate the influence of different components of motivation (intrinsic motivation, self-determination, self-efficacy and extrinsic -career and grade-motivation) on learning human histology in health science curricula and their relationship with the final performance of the students in histology. Methods: Glynn Science Motivation Questionnaire II was used to compare students' motivation components to learn histology in 367 first-year male and female undergraduate students enrolled in medical, dentistry and pharmacy degree programs. Results: For intrinsic motivation, career motivation and self-efficacy, the highest values corresponded to medical students, whereas dentistry students showed the highest values for self-determination and grade motivation. Genders differences were found for career motivation in medicine, self-efficacy in dentistry, and intrinsic motivation, self-determination and grade motivation in pharmacy. Career motivation and self-efficacy components correlated with final performance in histology of the students corresponding to the three curricula. Conclusions: Our results show that the overall motivational profile for learning histology differs among medical, dentistry and pharmacy students. This finding is potentially useful to foster their learning process, because if they are metacognitively aware of their motivation they will be better equipped to self-regulate their science-learning behavior in histology. This information could be useful for instructors and education policy makers to enhance curricula not only on the cognitive component of learning but also to integrate students' levels and types of motivation into the processes of planning, delivery and evaluation of medical education.This research was supported by the Unidad de Innovación Docente, University of Granada, Spain through grants UGR11-294 and UGR11-303

Oxidative coupling of methane to ethylene with 85% yield in a gas recycle electrocatalytic or catalytic reactor-separator

Methane was oxidatively coupled to ethylene with very high yield in a novel gas recycle reactor-separator operated in a batch or continuous flow mode. The recycled gas passes continuously through a molecular sieve trap in the recycle loop which adsorbs and thus protects from further oxidation a controllable percentage of ethylene and ethane. The products are obtained by subsequent heating of the molecular sieve trap. Ethylene yield up to 85%, i.e. 88% selectivity to ethylene at 97% CH4 conversion, has been obtained in the batch mode of operation using a Ag-Sm2O3 or Ag electrocatalyst and electrochemical supply of oxygen through a ZrO2-Y2O3 solid electrolyte. Using the continuous flow mode of operation with gaseous O-2 supply in the recycle loop and a Sr(1wt%)/La2O3 catalyst we have obtained ethylene yields up to 50%, i.e. 65% C2H4 selectivity at 76% CH4 conversion. The synergy of the catalytic and molecular sieve materials is discussed and modelled in view of the predominantly consecutive nature of the oxidative coupling of methane (OCM) network

The oxidative transformation of methane over the nickel-based catalysts modified by alkali metal oxide and rare earth metal oxide

Two completely different behaviors of the oxidative transformation of methane were performed over the nickel-based catalysts because of the different modifications by alkali metal oxide and rare earth metal oxide and the different interactions between nickel and supports, and two types of catalysts, namely the LiNiLaOx catalyst with a good Oxidative Coupling of Methane (OCM) performance and the LiNiLaOx/Al2O3 supported catalyst with an excellent performance of the Partial Oxidation of Methane to Syngas (POM) reaction were obtained. Several techniques, such as now-reaction, pulse-reaction, XRD, H-2-TPR, XPS, TPO, and TG, etc., were employed to investigate the relation among the preparation and composition of catalysts, the structures of catalysts and the catalytic performances, especially effects of each component, the active phases and their precursors, the redox behaviors and the states of nickel present in those nickel-based catalysts.' The effects of acid-base properties on the states of nickel present and on the directions of the oxidative transformation of methane, the interaction between nickel and other components and the deposition of surface carbon over catalysts were studied. The types of active centers, the modes of the activation of methane and the reaction mechanisms were discussed in detail

Uncertainty model and singularities of 3-2-1 wire-based tracking systems

This paper presents an ellipsoidal set-membership uncertainty model for wire-based tracking systems with wire length uncertainties and joint clearances. Although the proposed model is valid for any number of wires and configurations, including singularities, it has been particularized to a 3-2-1 parallel wire mechanism. The Euler’s tetrahedron formula has been used to obtain a numerically stable solution to the direct kinematics of this particular tracking system as well as a compact characterization of its singularities directly expressed in terms of the wire lengths. It is also shown that these singularities, when expressed in the configuration space of the moving element, can be identified as C-surfaces associated with the three basic contacts between polyhedra, which have been widely studied in the context of path planning

Manual versus mechanical cardiopulmonary resuscitation. An experimental study in pigs

<p>Abstract</p> <p>Background</p> <p>Optimal manual closed chest compressions are difficult to give. A mechanical compression/decompression device, named LUCAS, is programmed to give compression according to the latest international guidelines (2005) for cardiopulmonary resuscitation (CPR). The aim of the present study was to compare manual CPR with LUCAS-CPR.</p> <p>Methods</p> <p>30 kg pigs were anesthetized and intubated. After a base-line period and five minutes of ventricular fibrillation, manual CPR (n = 8) or LUCAS-CPR (n = 8) was started and run for 20 minutes. Professional paramedics gave manual chest compression's alternating in 2-minute periods. Ventilation, one breath for each 10 compressions, was given to all animals. Defibrillation and, if needed, adrenaline were given to obtain a return of spontaneous circulation (ROSC).</p> <p>Results</p> <p>The mean coronary perfusion pressure was significantly (p < 0.01) higher in the mechanical group, around 20 mmHg, compared to around 5 mmHg in the manual group. In the manual group 54 rib fractures occurred compared to 33 in the LUCAS group (p < 0.01). In the manual group one severe liver injury and one pressure pneumothorax were also seen. All 8 pigs in the mechanical group achieved ROSC, as compared with 3 pigs in the manual group.</p> <p>Conclusions</p> <p>LUCAS-CPR gave significantly higher coronary perfusion pressure and significantly fewer rib fractures than manual CPR in this porcine model.</p