Injectable laminin-functionalized hydrogel for nucleus pulposus regeneration.

Cell delivery to the pathological intervertebral disc (IVD) has significant therapeutic potential for enhancing IVD regeneration. The development of injectable biomaterials that retain delivered cells, promote cell survival, and maintain or promote an NP cell phenotype in vivo remains a significant challenge. Previous studies have demonstrated NP cell - laminin interactions in the nucleus pulposus (NP) region of the IVD that promote cell attachment and biosynthesis. These findings suggest that incorporating laminin ligands into carriers for cell delivery may be beneficial for promoting NP cell survival and phenotype. Here, an injectable, laminin-111 functionalized poly(ethylene glycol) (PEG-LM111) hydrogel was developed as a biomaterial carrier for cell delivery to the IVD. We evaluated the mechanical properties of the PEG-LM111 hydrogel, and its ability to retain delivered cells in the IVD space. Gelation occurred in approximately 20 min without an initiator, with dynamic shear moduli in the range of 0.9-1.4 kPa. Primary NP cell retention in cultured IVD explants was significantly higher over 14 days when cells were delivered within a PEG-LM111 carrier, as compared to cells in liquid suspension. Together, these results suggest this injectable laminin-functionalized biomaterial may be an easy to use carrier for delivering cells to the IVD

Cigarette smoke exposure facilitates allergic sensitization in mice

BACKGROUND: Active and passive smoking are considered as risk factors for asthma development. The mechanisms involved are currently unexplained. OBJECTIVE: The aim of this study was to determine if cigarette smoke exposure could facilitate primary allergic sensitization. METHODS: BALB/c mice were exposed to aerosolized ovalbumin (OVA) combined with air or tobacco smoke (4 exposures/day) daily for three weeks. Serology, lung cytopathology, cytokine profiles in bronchoalveolar lavage fluid (BALF) and on mediastinal lymph node cultures as well as lung function tests were performed after the last exposure. The natural history and the immune memory of allergic sensitization were studied with in vivo recall experiments. RESULTS: Exposure to OVA induced a small increase in OVA-specific serum IgE as compared with exposure to PBS (P < 0.05), while no inflammatory reaction was observed in the airways. Exposure to cigarette smoke did not induce IgE, but was characterized by a small but significant neutrophilic inflammatory reaction. Combining OVA with cigarette smoke not only induced a significant increase in OVA-specific IgE but also a distinct eosinophil and goblet cell enriched airway inflammation albeit that airway hyperresponsiveness was not evidenced. FACS analysis showed in these mice increases in dendritic cells (DC) and CD4(+ )T-lymphocytes along with a marked increase in IL-5 measured in the supernatant of lymph node cell cultures. Immune memory experiments evidenced the transient nature of these phenomena. CONCLUSION: In this study we show that mainstream cigarette smoke temporary disrupts the normal lung homeostatic tolerance to innocuous inhaled allergens, thereby inducing primary allergic sensitization. This is characterized not only by the development of persistent IgE, but also by the emergence of an eosinophil rich pulmonary inflammatory reaction

Between-group competition elicits within-group cooperation in children

Aggressive interactions between groups are frequent in human societies and can bear significant fitness costs and benefits (e.g. death or access to resources). During between-group competitive interactions, more cohesive groups (i.e. groups formed by individuals who cooperate in group defence) should out-perform less cohesive groups, other factors being equal (e.g. group size). The cost/benefit of between-group competition are thought to have driven correlated evolution of traits that favour between-group aggression and within-group cooperation (e.g. parochial altruism). Our aim was to analyse whether the proximate relationship between between-group competition and within-group cooperation is found in 3–10 years old children and the developmental trajectory of such a relationship. We used a large cohort of children (n = 120) and tested whether simulated between-group competition increased within-group cooperation (i.e. how much of a resource children were giving to their group companions) in two experiments. We found greater within-group cooperation when groups of four children were competing with other groups then in the control condition (no between-group competition). Within-group cooperation increased with age. Our study suggests that parochial altruism and in-group/out-group biases emerge early during the course of human development

Cooperation under Indirect Reciprocity and Imitative Trust

Indirect reciprocity, a key concept in behavioral experiments and evolutionary game theory, provides a mechanism that allows reciprocal altruism to emerge in a population of self-regarding individuals even when repeated interactions between pairs of actors are unlikely. Recent empirical evidence show that humans typically follow complex assessment strategies involving both reciprocity and social imitation when making cooperative decisions. However, currently, we have no systematic understanding of how imitation, a mechanism that may also generate negative effects via a process of cumulative advantage, affects cooperation when repeated interactions are unlikely or information about a recipient's reputation is unavailable. Here we extend existing evolutionary models, which use an image score for reputation to track how individuals cooperate by contributing resources, by introducing a new imitative-trust score, which tracks whether actors have been the recipients of cooperation in the past. We show that imitative trust can co-exist with indirect reciprocity mechanisms up to a threshold and then cooperation reverses -revealing the elusive nature of cooperation. Moreover, we find that when information about a recipient's reputation is limited, trusting the action of third parties towards her (i.e. imitating) does favor a higher collective cooperation compared to random-trusting and share-alike mechanisms. We believe these results shed new light on the factors favoring social imitation as an adaptive mechanism in populations of cooperating social actors

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

A Test of Evolutionary Policing Theory with Data from Human Societies

In social groups where relatedness among interacting individuals is low, cooperation can often only be maintained through mechanisms that repress competition among group members. Repression-of-competition mechanisms, such as policing and punishment, seem to be of particular importance in human societies, where cooperative interactions often occur among unrelated individuals. In line with this view, economic games have shown that the ability to punish defectors enforces cooperation among humans. Here, I examine a real-world example of a repression-of-competition system, the police institutions common to modern human societies. Specifically, I test evolutionary policing theory by comparing data on policing effort, per capita crime rate, and similarity (used as a proxy for genetic relatedness) among citizens across the 26 cantons of Switzerland. This comparison revealed full support for all three predictions of evolutionary policing theory. First, when controlling for policing efforts, crime rate correlated negatively with the similarity among citizens. This is in line with the prediction that high similarity results in higher levels of cooperative self-restraint (i.e. lower crime rates) because it aligns the interests of individuals. Second, policing effort correlated negatively with the similarity among citizens, supporting the prediction that more policing is required to enforce cooperation in low-similarity societies, where individuals' interests diverge most. Third, increased policing efforts were associated with reductions in crime rates, indicating that policing indeed enforces cooperation. These analyses strongly indicate that humans respond to cues of their social environment and adjust cheating and policing behaviour as predicted by evolutionary policing theory

Effects of laterally wedged insoles on symptoms and disease progression in medial knee osteoarthritis: a protocol for a randomised, double-blind, placebo controlled trial

<p>Abstract</p> <p>Background</p> <p>Whilst laterally wedged insoles, worn inside the shoes, are advocated as a simple, inexpensive, non-toxic self-administered intervention for knee osteoarthritis (OA), there is currently limited evidence to support their use. The aim of this randomised, double-blind controlled trial is to determine whether laterally wedges insoles lead to greater improvements in knee pain, physical function and health-related quality of life, and slower structural disease progression as well as being more cost-effective, than control flat insoles in people with medial knee OA.</p> <p>Methods/Design</p> <p>Two hundred participants with painful radiographic medial knee OA and varus malalignment will be recruited from the community and randomly allocated to lateral wedge or control insole groups using concealed allocation. Participants will be blinded as to which insole is considered therapeutic. Blinded follow up assessment will be conducted at 12 months after randomisation. The outcome measures are valid and reliable measures recommended for OA clinical trials. Questionnaires will assess changes in pain, physical function and health-related quality-of-life. Magnetic resonance imaging will measure changes in tibial cartilage volume. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log-book returned to the assessor on a monthly basis. To test the effect of the intervention using an intention-to-treat analysis, linear regression modelling will be applied adjusting for baseline outcome values and other demographic characteristics.</p> <p>Discussion</p> <p>Results from this trial will contribute to the evidence regarding the effectiveness of laterally wedged insoles for the management of medial knee OA.</p> <p>Trial registration</p> <p>ACTR12605000503628; NCT00415259.</p