A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog

Adjuvants are often composed of different constituents that can be divided into two groups based on their primary activity: the delivery system which carries and presents the vaccine antigen to antigen-presenting cells, and the immunostimulator that activates and modulates the ensuing immune response. Herein, we have investigated the importance of the delivery system and in particular its physical characteristics by comparing the delivery properties of two lipids which differ only in the degree of saturation of the acyl chains, rendering the liposomes either rigid (DDA, dimethyldioctadecylammonium) or highly fluid (DODA, dimethyldioleoylammonium) at physiological temperature. We show that these delivery systems are remarkably different in their ability to prime a Th1-directed immune response with the rigid DDA-based liposomes inducing a response more than 100 times higher compared to that obtained with the fluid DODA-based liposomes. Upon injection with a vaccine antigen, DDA-based liposomes form a vaccine depot that results in a continuous attraction of antigen-presenting cells that engulf a high amount of adjuvant and are subsequently efficiently activated as measured by an elevated expression of the co-stimulatory molecules CD40 and CD86. In contrast, the fluid DODA-based liposomes are more rapidly removed from the site of injection resulting in a lower up-regulation of co-stimulatory CD40 and CD86 molecules on adjuvant-positive antigen-presenting cells. Additionally, the vaccine antigen is readily dissociated from the DODA-based liposomes leading to a population of antigen-presenting cells that are antigen-positive but adjuvant-negative and consequently are not activated. These studies demonstrate the importance of studying in vivo characteristics of the vaccine components and furthermore show that physicochemical properties of the delivery system have a major impact on the vaccine-induced immune response. © 2012 Elsevier B.V. All rights reserved.

Changes in gene expression and morphology of mouse embryonic stem cells on differentiation into insulin-producing cells in vitro and in vivo

Background Embryonic stem (ES) cells have the potential to produce unlimited numbers of surrogate insulin-producing cells for cell replacement therapy of type I diabetes mellitus. The impact of the in vivo environment on mouse ES cell differentiation towards insulin-producing cells was analysed morphologically after implantation. Methods ES cells differentiated in vitro into insulin-producing cells according to the Lumelsky protocol or a new four-stage differentiation protocol were analysed morphologically before and after implantation for gene expression by in situ reverse transcription polymerase chain reaction and protein expression by immunohistochemistry and ultrastructural analysis. Results In comparison with nestin positive ES cells developed according to the reference protocol, the number of ES cells differentiated with the four-stage protocol increased under in vivo conditions upon morphological analysis. The cells exhibited, in comparison to the in vitro situation, increased gene and protein expression of Pdx1, insulin, islet amyloid polypeptide (IAPP), the GLUT2 glucose transporter and glucokinase, which are functional markers for glucose-induced insulin secretion of pancreatic beta cells. Renal sub-capsular implantation of ES cells with a higher degree of differentiation achieved by in vitro differentiation with a four-stage protocol enabled further significant maturation for the beta-cell-specific markers, insulin and the co-stored IAPP as well as the glucose recognition structures. in contrast, further in vivo differentiation was not achieved with cells differentiated in vitro by the reference protocol. Conclusions A sufficient degree of in vitro differentiation is an essential prerequisite for further substantial maturation in a beta-cell-specific way in vivo, supported by cell-cell contacts and vascularisation. Copyright (c) 2009 John Wiley & Sons, Ltd.

The N-terminus of CD14 acts to bind apoptotic cells and confers rapid-tethering capabilities on non-myeloid cells:CD14 and rapid tethering of apoptotic cells

Cell death and removal of cell corpses in a timely manner is a key event in both physiological and pathological situations including tissue homeostasis and the resolution of inflammation. Phagocytic clearance of cells dying by apoptosis is a complex sequential process comprising attraction, recognition, tethering, signalling and ultimately phagocytosis and degradation of cell corpses. A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within this process. The role of myeloid cell CD14 in mediating apoptotic cell interactions with macrophages has long been known though key molecules and residues involved have not been defined. Here we sought to further dissect the function of CD14 in apoptotic cell clearance. A novel panel of THP-1 cell-derived phagocytes was employed to demonstrate that CD14 mediates effective apoptotic cell interactions with macrophages in the absence of detectable TLR4 whilst binding and responsiveness to LPS requires TLR4. Using a targeted series of CD14 point mutants expressed in non-myeloid cells we reveal CD14 residue 11 as key in the binding of apoptotic cells whilst other residues are reported as key for LPS binding. Importantly we note that expression of CD14 in non-myeloid cells confers the ability to bind rapidly to apoptotic cells. Analysis of a panel of epithelial cells reveals that a number naturally express CD14 and that this is competent to mediate apoptotic cell clearance. Taken together these data suggest that CD14 relies on residue 11 for apoptotic cell tethering and it may be an important tethering molecule on so called 'non-professional' phagocytes thus contributing to apoptotic cell clearance in a non-myeloid setting. Furthermore these data establish CD14 as a rapid-acting tethering molecule, expressed in monocytes, which may thus confer responsiveness of circulating monocytes to apoptotic cell derived material. © 2013 Thomas et al.

Nootropia : a user profiling model based on a self-organising term network

Artificial Immune Systems are well suited to the problem of using a profile representation of an individual’s or a group’s interests to evaluate documents. Nootropia is a user profiling model that exhibits similarities to models of the immune system that have been developed in the context of autopoietic theory. It uses a self-organising term network that can represent a user’s multiple interests and can adapt to both short-term variations and substantial changes in them. This allows Nootropia to drift, constantly following changes in the user’s multiple interests, and, thus, to become structurally coupled to the user.

An enhanced functional ability questionnaire (faVIQ) to measure the impact of rehabilitation services on the visually impaired

AIM To develop a short, enhanced functional ability Quality of Vision (faVIQ) instrument based on previous questionnaires employing comprehensive modern statistical techniques to ensure the use of an appropriate response scale, items and scoring of the visual related difficulties experienced by patients with visual impairment. METHODS Items in current quality-of-life questionnaires for the visually impaired were refined by a multi-professional group and visually impaired focus groups. The resulting 76 items were completed by 293 visually impaired patients with stable vision on two occasions separated by a month. The faVIQ scores of 75 patients with no ocular pathology were compared to 75 age and gender matched patients with visual im pairm ent. RESULTS Rasch analysis reduced the faVIQ items to 27. Correlation to standard visual metrics was moderate (r=0.32-0.46) and to the NEI-VFQ was 0.48. The faVIQ was able to clearly discriminate between age and gender matched populations with no ocular pathology and visual impairment with an index of 0.983 and 95% sensitivity and 95% specificity using a cut off of 29. CONCLUSION The faVIQ allows sensitive assessm ent of quality-of-life in the visually im paired and should support studies which evaluate the effectiveness of low vision rehabilitation services. © Copyright International Journal of Ophthalmology Press.

Tunable coaxial resonators based on silicon optical fibers

Thermal tuning of a coaxial fiber resonator with a silica cladding surrounding an inner silicon core is investigated. By pumping the silicon with below bandgap light, it is possible to redshift the WGM resonances. © 2014 OSA.

In vitro assessment of the combined effect of eicosapentaenoic acid, green tea extract and curcumin C3 on protein loss in C2C12 myotubes

EPA has been clinically shown to reduce muscle wasting during cancer cachexia. This study investigates whether curcumin or green tea extract (GTE) enhances the ability of low doses of eicosapentaenoic acid (EPA) to reduce loss of muscle protein in an in vitro model. A low dose of EPA with minimal anti-cachectic activity was chosen to evaluate any potential synergistic effect with curcumin or GTE. Depression of protein synthesis and increase in degradation was determined in C2C12 myotubes in response to tumour necrosis factor-α (TNF-α) and proteolysis-inducing factor (PIF). EPA (50 μM) or curcumin (10 μg ml−1) alone had little effect on protein degradation caused by PIF but the combination produced complete inhibition, as did the combination with GTE (10 μg ml−1). In response to TNF-α (25 ng ml−1)-induced protein degradation, EPA had a small, but not significant effect on protein degradation; however, when curcumin and GTE were combined with EPA, the effect was enhanced. EPA completely attenuated the depression of protein synthesis caused by TNF-α, but not that caused by PIF. The combination of EPA with curcumin produced a significant increase in protein synthesis to both agents. GTE alone or in combination with EPA had no effect on the depression of protein synthesis by TNF-α, but did significantly increase protein synthesis in PIF-treated cells. Both TNF-α and PIF significantly reduced myotube diameter from 17 to 13 μm for TNF-α (23.5%) and 15 μm (11.8%) for PIF However the triple combination of EPA, curcumin and GTE returned diameters to values not significantly different from the control. These results suggest that either curcumin or GTE or the combination could enhance the anti-catabolic effect of EPA on lean body mass.

The effect of vision congruence on employee empowerment, commitment, satisfaction, and performance

Five models delineating the person-situation fit controversy were developed and tested. Hypotheses were tested to determine the linkages between vision congruence, empowerment, locus of control, job satisfaction, organizational commitment, and employee performance. Vision was defined as a mental image of a possible and desirable future state of the organization.^ Data were collected from 213 employees in a major flower import company. Participants were from various organizational levels and ethnic backgrounds. The data collection procedure consisted of three parts. First, a profile analysis instrument was used which was developed employing a Q-sort based technique, to measure the vision congruence between the CEO and each employee. Second, employees completed a survey instrument which included scales measuring empowerment, locus of control, job satisfaction, organizational commitment, and social desirability. Third, supervisor performance ratings were gathered from employee files. Data analysis consisted of using Kendall's tau to measure the correlation between CEO's and each employee's vision. Path analyses were conducted using the EQS structural equation program to test five theoretical models for goodness-of-fit. Regression analysis was employed to test whether locus of control acted as a moderator variable.^ The results showed that vision congruence is significantly related to job satisfaction and employee commitment, and perceived empowerment acts as an intervening variable affecting employee outcomes. The study also found that people with an internal locus of control were more likely to feel empowered than were those with external beliefs. Implications of these findings for both researchers and practitioners are discussed and suggestions for future research directions are provided. ^

Evaluating heavy episodic drinking effects on educational attainment

Adolescence and emerging adulthood are transition points that offer both opportunities and constraints on individual development. The purpose of this study is threefold: First, to examine two models (i.e., young adolescents in grades 7 and 8 and older adolescents in grade 12) of heavy episodic drinking and examine how heavy episodic drinking affects subsequent educational attainment. By utilizing two different developmental transitions, i.e., middle school to high school and high school to college, it may be possible to better understand the temporal effects of alcohol use and subsequent educational attainment. The second purpose of this study is to examine how alcohol use at Time 1 may lead to the problems in the adolescent's immediate context due to alcohol (i.e., problems with parents, peers, romantic relationships, problems at school) and to examine if these problems affect educational attainment over and above alcohol use alone. The third purpose of this study is to examine the potential gender differences in these models. The study uses data from the National Longitudinal Study of Adolescent Health, which is a large scale, nationally representative school based sample of 20,745 adolescents who were interviewed in grades 7 to 12. Two longitudinal mediational models were evaluated utilizing structural equation modeling. Binge drinking and number of days drunk were used as indicators for a latent variable of heavy episodic drinking (i.e., LHED). In the 7th and 8th grade model, direct effects of LHED were found to predict educational attainment at grade 12. Additionally, in the 7th and 8th grade sample, a mediated relationship was found whereby educational attainment was predicted by problems with parents. Problems with parents were predicted by number of days drunk in the past year. In the 12th grade sample, there were no direct effects or indirect effects of alcohol on educational attainment. This study highlights the need for using a longitudinal framework when examining heavy episodic drinking's effects on educational attainment. ^

An examination of the effects of a summer book-reading program on the language and early literacy outcomes of toddlers from high risk environments

The current study examined the impact of an early summer literacy program and the mediating effects of the home literacy environment on the language and literacy outcomes of a group of children at-risk for long-term developmental and academic delays. Participating children (n=54) were exposed to an intensive book-reading intervention each summer (June through mid August) over a 3-year period. The current study implemented an ex post facto, quasi-experimental design. This nonequivalent group design involved a pretest and posttest over three time points for a non-randomized treatment group and a matched non-treatment comparison group. Results indicated that literacy scores did improve for the children over the 3-year period; however, language scores did not experience the same rate of change over time. Receptive language was significantly impacted by attendance, and race/ethnicity. Expressive language was impacted significantly by gestational age and attendance. Results also indicated that language outcomes for young children who are exposed to a literacy program were higher than those who did not participate; however, only receptive language yielded significance at the p<.05 level. These study results also found that activities in the home that support literacy and learning do indeed impact language and literacy outcomes for these children, specifically, the age at which a child is read to, the number of books in the home, a child’s enjoyment of reading, and whether a child looks at books on his or her own impact language scores. This study concluded that at-risk young children do benefit from center-based literacy intervention. This literacy experience, however, is also driven by the children's home environment, their attendance to the program, whether they were premature or not and the type of caregiver.

Disturbance and the rising tide: the challenge of biodiversity management on low-island ecosystems

Sea-level rise presents an imminent threat to freshwater-dependent ecosystems on small oceanic islands, which often harbor rare and endemic taxa. Conservation of these assemblages is complicated by feedbacks between sea level and recurring pulse disturbances (eg hurricanes, fire). Once sea level reaches a critical level, the transition from a landscape characterized by mesophytic upland forests and freshwater wetlands to one dominated by mangroves can occur suddenly, following a single storm-surge event. We document such a trajectory, unfolding today in the Florida Keys. With sea level projected to rise substantially during the next century, ex-situ actions may be needed to conserve individual species of special concern. However, within existing public conservation units, managers have a responsibility to conserve extant biodiversity. We propose a strategy that combines the identification and intensive management of the most defensible core sites within a broader reserve system, in which refugia for biota facing local extirpation may be sought.

Herbivore and nutrient impact on primary producer assemblages in a tropical marine environment

Globally, human populations are increasing and coastal ecosystems are becoming increasingly impacted by anthropogenic stressors. As eutrophication and exploitation of coastal resources increases, primary producer response to these drivers becomes a key indicator of ecosystem stability. Despite the importance of monitoring primary producers such as seagrasses and macroalgae, detailed studies on the response of these benthic habitat components to drivers remain relatively sparse. Utilizing a multi-faceted examination of turtle-seagrass and sea urchin-macroalgae consumer and nutrient dynamics, I elucidate the impact of these drivers in Akumal, Quintana Roo, Mexico. In Yal Ku Lagoon, macroalgae bioindicators signified high nutrient availability, which is important for further studies, but did not consistently follow published trends reflecting decreased δ 15N content with distance from suspected source. In Akumal Bay, eutrophication and grazing by turtles and fishes combine to structure patches within the seagrass beds. Grazed seagrass patches had higher structural complexity and productivity than patches continually grazed by turtles and fishes. Results from this study indicate that patch abandonment may follow giving-up density theory, the first to be recorded in the marine environment. As Diadema antillarum populations recover after their massive mortality thirty years ago, the role these echinoids will have in reducing macroalgae cover and altering ecosystem state remains to be clear. Although Diadema antillarum densities within the coral reef ecosystem were comparable to other regions within the Caribbean, the echinoid population in Akumal Bay was an insufficient driver to prevent dominance of a turf-algal-sediment (TAS) state. After a four year study, declining coral cover coupled with increased algal cover suggests that the TAS-dominated state is likely to persist over time despite echinoid recovery. Studies on macroalgal diversity and nutrients within this same region of echinoids indicated diversity and nutrient content of macroalgae increased, which may further increase the persistence of the algal-dominated state. This study provides valuable insight into the variable effects of herbivores and nutrients on primary producers within a tropical coastal ecosystem. Results from this work challenge many of the currently accepted theories on primary producer response to nutrients and herbivory while providing a framework for further studies into these dynamics.