Anti-angiogenic potential of VEGF blocker dendron-laden gellan gum hydrogels for tissue engineering applications

Damage of non-vascularised tissues such as cartilage and cornea can result in healing processes accompanied by a non-physiological angiogenesis. Peptidic aptamers have recently been reported to block the vascular endothelial growth factor (VEGF). However, the therapeutic applications of these aptamers is limited due to their short half-life in vivo. In this work, an enhanced stability and bioavailability of a known VEGF blocker aptamer sequence (WHLPFKC) was pursued through its tethering of molecular scaffolds based on hyperbranched peptides, the poly(É -lysine) dendrons, bearing three branching generations. The proposed design allowed simultaneous and orderly-spaced exposure of sixteen aptamers per dendrimer to the surrounding biological microenvironent, as well as a relatively hydrophobic core based on di-phenylalanine aiming to promote an hydrophobic interaction with the hydrophobic moieties of ionically-crosslinked metacrylated gellan gum (iGG-MA) hydrogels. The VEGF blocker dendrons were entrapped in iGG-MA hydrogels and their capacity to prevent endothelial cell sprouting was assessed qualitatively and quantitatively using 3D in vitro models and the in vivo chick chorioallantoic membrane (CAM) assay. The data demonstrate that at nanoscale concentrations, the dendronised structures were able to enhance control of the biological actvity of WHLPFKC at the material/tissue interface and hence the anti-angiogenic capacity of iGG-MA hydrogels not only preventing blood vessel invasion, but also inducing their regression at the tissue/iGG-MA interface. The in ovo study confirmed that iGG-MA functionalised with the dendron VEGF blockers do inhibit angiogenesis by controlling both size and ramifications of blood vessels in proximity of the implanted gel surface.This work was mainly supported by the EC FP7 project Disc Regeneration (Contract No NMP3-LA-2008-213904). This study was also funded by the EC FP7 Programme contract agreement no REGPOT-CT2012-316331-POLARIS

Functionalisation of methacrylated gellan gum hydrogels by anti-angiogenic dendrons

The regeneration of cartilage in the intervertebral disc nucleus pulposus and joints is impaired by the formation of fibrocartilage that is caused by the invasion of the tissue by blood vessels. Peptides have been identified by phage display technique which are able to bind VEGF thus inhibiting angiogenesis. The present works focusses on the synthesis of poly(epsilon-lysine) dendrons of three branching generations in which the molecular root of the dendron bears a di-phenylalanine sequence to promote hydrophobic interactions with material surfaces and the uppermost molecular branches are functionalised with the amino acid sequenceWHLPFKC that is known to block VEGF. These biofunctionalised dendrons were entrapped in methacrylated Gellan Gum (GG-MA) hydrogels and tested for their ability to inhibit endothelial cell sprouting by both a 3D in vitro cell models and an in ovo model. The results show that when GG-MA is functionalised with the dendronised VEGF blockers, a regression of angiogenesis takes place around the hydrogel boundary. The in ovo study supports these findings as the GG-MA functionalised with the dendronised VEGF blockers did not elicit any acute inflammatory response, and decrease the number of converging macroscopic blood vessels as compared to positive controls. Moreover, the hydrogels prevented the infiltration of blood vessels, after 4 days of implantation.Fundação para a Ciência e TecnologiaEU 7th Framework ProgrammeMICINNJunta de Castilla y LeónCIBER-BBNFundo Social EuropeuPrograma Operacional Potencial Human

Heritable risk factors associated with language impairments

There is a strong genetic contribution to children’s language and literacy impairments. The aim of this study was to determine which aspects of the phenotype are familial by comparing 34 parents of probands with language/literacy impairments and 33 parents of typically developing probands. The parents responded to questionnaires regarding previous history for language/reading impairment and participated in psychometric testing. The psychometric test battery consisted of tests assessing non-verbal IQ, short-term memory, articulation, receptive grammar, reading abilities and spelling. Self-report measures demonstrated a higher prevalence of language and literacy impairments in parents of affected probands (32%) compared with parents of unaffected probands (6%). The two groups of parents differed significantly in their performance on the non-word repetition, oromotor and digit span tasks. Non-word repetition gave the best discrimination between the parent groups even when the data from the parents who actually were impaired as ascertained by direct testing or self-report were removed from the analyses. This suggests that non-word repetition serves as a marker of a family risk for language impairment. The paper concludes with a discussion of issues associated with ascertainment of specific language impairment (SLI)

Dielectric barrier plasma discharge exsolution of nanoparticles at room temperature and atmospheric pressure Dataset

The dataset that corresponds to the results reported in the paper are included within this record as an Excel file and with tabs corresponding to each figure. Additional results and raw data underlying this work (full set of microscopy images and size analysis and statistics, high resolution deconvoluted x-ray photoelectron spectra and control magnetic measurements) are available in the Supporting Information (in PDF format) or on request following instructions provided here. This work has been supported by EPSRC through the UK Catalysis Hub (EP/R027129/1) and the Emergent Nanomaterials-Critical Mass Initiative (EP/R023638/1, EP/R023921/1, EP/R023522/1, EP/R008841/1) as well as the Royal Society (IES\R2\212049). F.F. gratefully acknowledges support from the National Research Council of Italy (2020 STM program). I.S.M. acknowledges funding from the Royal Academy of Engineering through a Chair in Emerging Technologies Award entitled “Engineering Chemical Reactor Technologies for a Low-Carbon Energy Future” (Grant CiET1819\2\57). KK acknowledges funding from the Henry Royce Institute (EP/X527257/1)

Effects of Total Resources, Resource Ratios, and Species Richness on Algal Productivity and Evenness at Both Metacommunity and Local Scales

The study of the interrelationship between productivity and biodiversity is a major research field in ecology. Theory predicts that if essential resources are heterogeneously distributed across a metacommunity, single species may dominate productivity in individual metacommunity patches, but a mixture of species will maximize productivity across the whole metacommunity. It also predicts that a balanced supply of resources within local patches should favor species coexistence, whereas resource imbalance would favor the dominance of one species. We performed an experiment with five freshwater algal species to study the effects of total supply of resources, their ratios, and species richness on biovolume production and evenness at the scale of both local patches and metacommunities. Generally, algal biovolume increased, whereas algal resource use efficiency (RUE) and evenness decreased with increasing total supply of resources in mixed communities containing all five species. In contrast to predictions for biovolume production, the species mixtures did not outperform all monocultures at the scale of metacommunities. In other words, we observed no general transgressive overyielding. However, RUE was always higher in mixtures than predicted from monocultures, and analyses indicate that resource partitioning or facilitation in mixtures resulted in higher-than-expected productivity at high resource supply. Contrasting our predictions for the local scale, balanced supply of resources did not generally favor higher local evenness, however lowest evenness was confined to patches with the most imbalanced supply. Thus, our study provides mixed support for recent theoretical advancements to understand biodiversity-productivity relationships

Connecting the Dots: Responses of Coastal Ecosystems to Changing Nutrient Concentrations

Empirical relationships between phytoplankton biomass and nutrient concentrations established across a wide range of different ecosystems constitute fundamental quantitative tools for predicting effects of nutrient management plans. Nutrient management plans based on such relationships, mostly established over trends of increasing rather than decreasing nutrient concentrations, assume full reversibility of coastal eutrophication. Monitoring data from 28 ecosystems located in four well-studied regions were analyzed to study the generality of chlorophyll a versus nutrient relationships and their applicability for ecosystem management. We demonstrate significant differences across regions as well as between specific coastal ecosystems within regions in the response of chlorophyll a to changing nitrogen concentrations. We also show that the chlorophyll a versus nitrogen relationships over time constitute convoluted trajectories rather than simple unique relationships. The ratio of chlorophyll a to total nitrogen almost doubled over the last 30-40 years across all regions. The uniformity of these trends, or shifting baselines, suggest they may result from large-scale changes, possibly associated with global climate change and increasing human stress on coastal ecosystems. Ecosystem management must, therefore, develop adaptation strategies to face shifting baselines and maintain ecosystem services at a sustainable level rather than striving to restore an ecosystem state of the past. © 2011 American Chemical Society.This research is a contribution to the Thresholds Integrated Project (contract FP6-003933-2) and WISER (contract FP7-226273), funded by the European Commission.Peer Reviewe