Seasonal species richness of birds on the world's islands and its geographical correlates

The presence of migratory birds on islands results in seasonal variation in species richness. These patterns and their geographical correlates within the context of island biogeography theory have not been examined. We used 21 years of bird observations on 690 islands from eBird to determine how seasonal species richness estimates vary as a function of island area, isolation and latitude. Species richness was highest on islands within the northern mid-latitudes during migration and on islands within tropical latitudes during the non-breeding season. Area defined positive, nonlinear relationships with species richness across seasons, with the steepest slopes occurring with islands greater than 1100 km2. Distance to mainland defined negative, nonlinear relationships with species richness across seasons, with the strongest slopes occurring with islands located greater than 150 km from the mainland. Species-area relationships were weakest for the most remote islands and strongest for islands at intermediate distances to the mainland. Intermediate proximity to other islands was a poor predictor of species richness. Our findings emphasize the presence of seasonally dynamic geographical relationships, the enhanced role of evolutionary processes on larger islands, the unique ecology of the world's most remote islands, and the importance of islands as stopover sites and wintering grounds for migratory bird species

Avidin as a model for charge driven transport into cartilage and drug delivery for treating early stage post-traumatic osteoarthritis

Local drug delivery into cartilage remains a challenge due to its dense extracellular matrix of negatively charged proteoglycans enmeshed within a collagen fibril network. The high negative fixed charge density of cartilage offers the unique opportunity to utilize electrostatic interactions to augment transport, binding and retention of drug carriers. With the goal of developing particle-based drug delivery mechanisms for treating post-traumatic osteoarthritis, our objectives were, first, to determine the size range of a variety of solutes that could penetrate and diffuse through normal cartilage and enzymatically treated cartilage to mimic early stages of OA, and second, to investigate the effects of electrostatic interactions on particle partitioning, uptake and binding within cartilage using the highly positively charged protein, Avidin, as a model. Results showed that solutes having a hydrodynamic diameter ≤10 nm can penetrate into the full thickness of cartilage explants while larger sized solutes were trapped in the tissue's superficial zone. Avidin had a 400-fold higher uptake than its neutral same-sized counterpart, NeutrAvidin, and >90% of the absorbed Avidin remained within cartilage explants for at least 15 days. We report reversible, weak binding (K[subscript D] ~ 150 μm) of Avidin to intratissue sites in cartilage. The large effective binding site density (N[subscript T] ~ 2920 μm) within cartilage matrix facilitates Avidin's retention, making its structure suitable for particle based drug delivery into cartilage

Transport and equilibrium uptake of a peptide inhibitor of PACE4 into articular cartilage is dominated by electrostatic interactions

The availability of therapeutic molecules to targets within cartilage depends on transport through the avascular matrix. We studied equilibrium partitioning and non-equilibrium transport into cartilage of Pf-pep, a 760 Da positively charged peptide inhibitor of the proprotein convertase PACE4. Competitive binding measurements revealed negligible binding of Pf-pep to sites within cartilage. Uptake of Pf-pep depended on glycosaminoglycan charge density, and was consistent with predictions of Donnan equilibrium given the known charge of Pf-pep. In separate transport experiments, the diffusivity of Pf-pep in cartilage was measured to be ~1 × 10[superscript −6] cm[superscript 2]/s, close to other similarly-sized non-binding solutes. These results suggest that small positively charged therapeutics will have a higher concentration within cartilage than in the surrounding synovial fluid, a desired property for local delivery; however, such therapeutics may rapidly diffuse out of cartilage unless there is additional specific binding to intra-tissue substrates that can maintain enhanced intra-tissue concentration for local delivery.National Institutes of Health (U.S.) (Grant AR45779)National Institutes of Health (U.S.) (Grant AR33236)Pfizer Inc

High-bandwidth AFM-based rheology is a sensitive indicator of early cartilage aggrecan degradation relevant to mouse models of osteoarthritis

Murine models of osteoarthritis (OA) and post-traumatic OA have been widely used to study the development and progression of these diseases using genetically engineered mouse strains along with surgical or biochemical interventions. However, due to the small size and thickness of murine cartilage, the relationship between mechanical properties, molecular structure and cartilage composition has not been well studied. We adapted a recently developed AFM-based nano-rheology system to probe the dynamic nanomechanical properties of murine cartilage over a wide frequency range of 1 Hz to 10 kHz, and studied the role of glycosaminoglycan (GAG) on the dynamic modulus and poroelastic properties of murine femoral cartilage. We showed that poroelastic properties, highlighting fluid–solid interactions, are more sensitive indicators of loss of mechanical function compared to equilibrium properties in which fluid flow is negligible. These fluid-flow-dependent properties include the hydraulic permeability (an indicator of the resistance of matrix to fluid flow) and the high frequency modulus, obtained at high rates of loading relevant to jumping and impact injury in vivo. Utilizing a fibril-reinforced finite element model, we estimated the poroelastic properties of mouse cartilage over a wide range of loading rates for the first time, and show that the hydraulic permeability increased by a factor ~16 from k[subscript normal] = 7.80 × 10[superscript −16] ± 1.3 × 10[superscript −16] m[superscript 4]/N s to k[subscript GAG-depleted] = 1.26 × 10[superscript −14] ± 6.73 × 10[superscript −15] m[superscript 4]/N s after GAG depletion. The high-frequency modulus, which is related to fluid pressurization and the fibrillar network, decreased significantly after GAG depletion. In contrast, the equilibrium modulus, which is fluid-flow independent, did not show a statistically significant alteration following GAG depletion.National Institutes of Health (U.S.) (Grant 060331)Whitaker Foundation (Health Sciences Fund Fellowship)Arthritis Australi

The SINS Survey: Broad Emission Lines in High-Redshift Star-Forming Galaxies

High signal-to-noise, representative spectra of star-forming galaxies at z~2, obtained via stacking, reveal a high-velocity component underneath the narrow H-alpha and [NII] emission lines. When modeled as a single Gaussian, this broad component has FWHM > 1500 km/s; when modeled as broad wings on the H-alpha and [NII] features, it has FWHM > 500 km/s. This feature is preferentially found in the more massive and more rapidly star-forming systems, which also tend to be older and larger galaxies. We interpret this emission as evidence of either powerful starburst-driven galactic winds or active supermassive black holes. If galactic winds are responsible for the broad emission, the observed luminosity and velocity of this gas imply mass outflow rates comparable to the star formation rate. On the other hand, if the broad line regions of active black holes account for the broad feature, the corresponding black holes masses are estimated to be an order of magnitude lower than those predicted by local scaling relations, suggesting a delayed assembly of supermassive black holes with respect to their host bulges.Comment: 11 pages, 5 figures. Accepted version, incorporating referee comments, including changes to title, abstract, figures, and discussion sectio

Stress-vs-time signals allow the prediction of structurally catastrophic events during fracturing of immature cartilage and predetermine the biomechanical, biochemical, and structural impairment

Objective Trauma-associated cartilage fractures occur in children and adolescents with clinically significant incidence. Several studies investigated biomechanical injury by compressive forces but the injury-related stress has not been investigated extensively. In this study, we hypothesized that the biomechanical stress occurring during compressive injury predetermines the biomechanical, biochemical, and structural consequences. We specifically investigated whether the stress-vs-time signal correlated with the injurious damage and may allow prediction of cartilage matrix fracturing. Methods Superficial and deeper zones disks (SZDs, DZDs; immature bovine cartilage) were biomechanically characterized, injured (50% compression, 100%/s strain-rate), and re-characterized. Correlations of the quantified functional, biochemical and histological damage with biomechanical parameters were zonally investigated. Results Injured SZDs exhibited decreased dynamic stiffness (by 93.04 ± 1.72%), unresolvable equilibrium moduli, structural damage (2.0 ± 0.5 on a 5-point-damage-scale), and 1.78-fold increased sGAG loss. DZDs remained intact. Measured stress-vs-time-curves during injury displayed 4 distinct shapes, which correlated with histological damage (p < 0.001), loss of dynamic stiffness and sGAG (p < 0.05). Damage prediction in a blinded experiment using stress-vs-time grades was 100%-correct and sensitive to differentiate single/complex matrix disruptions. Correlations of the dissipated energy and maximum stress rise with the extent of biomechanical and biochemical damage reached significance when SZDs and DZDs were analyzed as zonal composites but not separately. Conclusions The biomechanical stress that occurs during compressive injury predetermines the biomechanical, biochemical, and structural consequences and, thus, the structural and functional damage during cartilage fracturing. A novel biomechanical method based on the interpretation of compressive yielding allows the accurate prediction of the extent of structural damage.National Institutes of Health (U.S.) (Grant R01-AR45779)Deutsche Forschungsgemeinschaft (Grant RO2511/1-1)Deutsche Forschungsgemeinschaft (Grant RO2511/2-1)Germany. Federal Ministry of Education and Research (Grant 01KQ0902B TP2

Transport of anti-IL-6 antigen binding fragments into cartilage and the effects of injury

The efficacy of biological therapeutics against cartilage degradation in osteoarthritis is restricted by the limited transport of macromolecules through the dense, avascular extracellular matrix. The availability of biologics to cell surface and matrix targets is limited by steric hindrance of the matrix, and the microstructure of matrix itself can be dramatically altered by joint injury and the subsequent inflammatory response. We studied the transport into cartilage of a 48 kDa anti-IL-6 antigen binding fragment (Fab) using an in vitro model of joint injury to quantify the transport of Fab fragments into normal and mechanically injured cartilage. The anti-IL-6 Fab was able to diffuse throughout the depth of the tissue, suggesting that Fab fragments can have the desired property of achieving local delivery to targets within cartilage, unlike full-sized antibodies which are too large to penetrate beyond the cartilage surface. Uptake of the anti-IL-6 Fab was significantly increased following mechanical injury, and an additional increase in uptake was observed in response to combined treatment with TNFα and mechanical injury, a model used to mimic the inflammatory response following joint injury. These results suggest that joint trauma leading to cartilage degradation can further alter the transport of such therapeutics and similar-sized macromolecules.National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (Grant AR45779)National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (Grant AR60331)Janssen Pharmaceutical Ltd. (Research and Development Grant