Peptide-functionalized polymeric nanoparticles for active targeting of damaged tissue in animals with experimental autoimmune encephalomyelitis

Increased permeability of blood vessels is an indicator for various injuries and diseases, including multiple sclerosis (MS), of the central nervous system. Nanoparticles have the potential to deliver drugs locally to sites of tissue damage, reducing the drug administered and limiting associated side effects, but efficient accumulation still remains a challenge. We developed peptide-functionalized polymeric nanoparticles to target blood clots and the extracellular matrix molecule nidogen, which are associated with areas of tissue damage. Using the induction of experimental autoimmune encephalomyelitis in rats to provide a model of MS associated with tissue damage and blood vessel lesions, all targeted nanoparticles were delivered systemically. In vivo data demonstrates enhanced accumulation of peptide functionalized nanoparticles at the injury site compared to scrambled and naive controls, particularly for nanoparticles functionalized to target fibrin clots. This suggests that further investigations with drug laden, peptide functionalized nanoparticles might be of particular interest in the development of treatment strategies for MS.

Hierarchically structured porous poly(2-oxazoline) hydrogels

A new method for fabricating hydrogels with intricate control over hierarchical 3D porosity using micro-fiber porogens is presented. Melt electrospinning writing of poly(ε-caprolactone) is used to create the sacrificial template leading to hierarchical structuring consisting of pores inside the denser poly(2-oxazoline) hydrogel mesh. This versatile approach provides new opportunities to create well-defined multilevel control over interconnected pores with diameters in the lower micrometer range inside hydrogels with potential applications as cell scaffolds with tunable diffusion and transport of, e.g. nutrients, growth factors or therapeutics.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Risk analysis of prostate cancer in PRACTICAL, a multinational consortium, using 25 known prostate cancer susceptibility loci

Background Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. Methods We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS).We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived agespecific absolute risks of developing prostate cancer by PRS stratum and family history. Results The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Conclusions Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact:We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.

Perylene-based profluorescent nitroxides for the rapid monitoring of polyester degradation upon weathering: An assessment

A profluorescent nitroxide possessing an isoindoline nitroxide moiety linked to a perylene fluorophore was developed to monitor radical mediated degradation of melamine-formaldehyde crosslinked polyester coil coatings in an industry standard accelerated weathering tester. Trapping of polyester-derived radicals (most likely C-radicals) that are generated during polymer degradation leads to fluorescent closed-shell alkoxy amines, which was used to obtain time-dependent degradation profiles to assess the relative stability of different polyesters towards weathering. The nitroxide probe couples excellent thermal stability and satisfactory photostability with high sensitivity and enables detection of free radical damage in polyesters under conditions that mimic exposure to the environment on a time scale of hours rather than months or years required by other testing methods. There are indications that the profluorescent nitroxide undergoes partial photo-degradation in the absence of polymer-derived radicals. Unexpectedly, it was also found that UV-induced fragmentation of the NO–C bond in closed-shell alkoxy amines leads to regeneration of the profluorescent nitroxide and the respective C-radical. The maximum fluorescence intensity that could be achieved with a given probe concentration is therefore not only determined by the amount of polyester radicals formed during accelerated weathering, but also by the light-driven side reactions of the profluorescent nitroxide and the corresponding alkoxy amine radical trapping products. Studies to determine the optimum probe concentration in the polymer matrix revealed that aggregation and re-absorption effects lowered the fluorescence intensity at higher concentrations of the profluorescent nitroxide, but too low probe concentrations, where these effects would be avoided, were not sufficient to trap the amount of polyester radicals formed upon weathering. The optimized experimental conditions were used to assess the impact of temperature and UV irradiance on polymer degradation during accelerated weathering.

Does manure management affect the latent greenhouse gas emitting potential of livestock manures?

With livestock manures being increasingly sought as alternatives to costly synthetic fertilisers, it is imperative that we understand and manage their associated greenhouse gas (GHG) emissions. Here we provide the first dedicated assessment into how the GHG emitting potential of various manures responds to the different stages of the manure management continuum (e.g., from feed pen surface vs stockpiled). The research is important from the perspective of manure application to agricultural soils. Manures studied included: manure from beef feedpen surfaces and stockpiles; poultry broiler litter (8-week batch); fresh and composted egg layer litter; and fresh and composted piggery litter. Gases assessed were methane (CH4) and nitrous oxide (N2O), the two principal agricultural GHGs. We employed proven protocols to determine the manures’ ultimate CH4 producing potential. We also devised a novel incubation experiment to elucidate their N2O emitting potential; a measure for which no established methods exist. We found lower CH4 potentials in manures from later stages in their management sequence compared with earlier stages, but only by a factor of 0.65×. Moreover, for the beef manures this decrease was not significant (P < 0.05). Nitrous oxide emission potential was significantly positively (P < 0.05) correlated with C/N ratios yet showed no obvious relationship with manure management stage. Indeed, N2O emissions from the composted egg manure were considerably (13×) and significantly (P < 0.05) higher than that of the fresh egg manure. Our study demonstrates that manures from all stages of the manure management continuum potentially entail significant GHG risk when applied to arable landscapes. Efforts to harness manure resources need to account for this.

Extract from plants

An extract of organic material from a species selected from the tribe Nicotianeae that comprises a mixture of C26 to C33 alkanes at a purity of at least 90% by volume of total extract.

Home range and habitat use by Kemp's Ridley turtles in West-Central Florida

The Kemp's ridley turtle (Lepidochelys kempii) is an endangered species whose recovery depends in part on the identification and protection of required habitats. We used radio and sonic telemetry on subadult Kemp's ridley turtles to investigate home-range size and habitat use in the coastal waters of west-central Florida from 1994 to 1996. We tracked 9 turtles during May-August up to 70 days after release and fou.ld they occupied 5-30 km2 foraging ranges. Compositional analyses indicated that turtles used rock outcroppings in their foraging ranges at a significantly higher proportion than expected. based on availability within the study area. Additionally. turtles used live bottom (e.g .• sessile invertebrates) and green macroalgae habitats significantly more than seagrass habitat. Similar studies are needed through'mt the Kemp's ridley turtles' range to investigate regional and stage-specific differences in habitat use. which can then be used to conserve important foraging areas.

Variability in spawning frequency and reproductive development of the narrow-barred Spanish mackerel (Scomberomorus commerson) along the west coast of Australia

The narrow-barred Spanish mackerel (Scomberomorus commerson) is widespread throughout the Indo-West Pacific region. This study describes the reproductive biology of S. commerson along the west coast of Australia, where it is targeted for food consumption and sports fishing. Development of testes occurred at a smaller body size than for ovaries, and more than 90% of males were sexually mature by the minimum legal length of 900 mm TL compared to 50% of females. Females dominated overall catches although sex ratios within daily catches vary considerably and females were rarely caught when spaw n ing. Scomberomorus commerson are seasonally abundant in coastal waters and most of the commercial catch is taken prior to the reproductive season. Spawning occurs between about August and November in the Kimberley region and between October and January in the Pilbara region. No spawning activity was recorded in the more southerly West Coast region, and only in the north Kimberley region were large numbers of fish with spawning gonads collected. Catches dropped to a minimum when spawning began in the Pilbara region, when fish became less abundant in inshore waters and inclement weather conditions limited fishing on still productive offshore reefs. Final maturation and ovulation of oocytes took place within a 24-hour period, and females spawned in the afternoon-evening every three days. A third of these spawning females released batches of eggs on consecutive days. Relationships between length, weight, and batch fecundity are presented.

Application of an acoustic–trawl survey design to improve estimates of rockfish biomass

Biomass estimates of several species of Alaskan rockfishes exhibit large interannual variations. Because rockfishes are long lived and relatively slow growing, large, short-term shifts in population abundance are not likely. We attribute the variations in biomass estimates to the high variability in the spatial distribution of rockfishes that is not well accounted for by the survey design currently used. We evaluated the performance of an experimental survey design, the Trawl and Acoustic Presence/Absence Survey (TAPAS), to reduce the variability in estimated biomass for Pacific ocean perch (Sebastes alutus). Analysis of archived acoustic backscatter data produced an acoustic threshold for delineating potential areas of high (“patch”) and low (“background���) catch per unit of effort (CPUE) in real time. In 2009, we conducted a 12-day TAPAS near Yakutat, Alaska. We completed 59 trawls at 19 patch stations and 40 background stations. The design performed well logistically, and Pacific ocean perch (POP) accounted for 55% of the 31 metric tons (t) of the catch from this survey. The resulting estimates of rockfish biomass were slightly less precise than estimates from simple random sampling. This difference in precision was due to the weak relationship of CPUE to mean volume backscattering and the relatively low variability of POP CPUE encountered. When the data were re-analyzed with a higher acoustic threshold than the one used in the field study, performance was slightly better with this revised design than with the original field design. The TAPAS design could be made more effective by establishing a stronger link between acoustic backscatter and CPUE and by deriving an acoustic threshold that allows better identification of backscatter as that from the target species.