Search

While juvenile white sharks (JWS) can display regional endothermy, the need to maintain internal temperatures within an energetically favorable range likely drives thermoregulatory movements to maximize growth and foraging efficiency. Many JWS from the northeastern Pacific population aggregate seasonally in nearshore nursery habitats throughout the Southern California Bight and historic data show that inter-seasonal movement patterns may be heavily dependent on ambient water temperature. However, the degree to which micro-scale (e.g., ~10 m²) water temperature heterogeneity influences JWS three-dimensional movement within nearshore aggregation sites is unknown. High-resolution temperature and passive acoustic-telemetry geo-positional data were used to quantify how temperature and vertical thermal stratification influenced JWS movement using several modeling approaches. JWS selected for water temperatures between 16 - 22°C and depths shallower than 2 m. Sharks occupied deeper waters during dawn and dusk periods, and their distance from the seafloor and spatial orientation of their depth distribution was significantly related to the thermal structure of the water column across the monitored area. Tagged sharks remained above a 16°C thermal threshold and altered their horizontal and vertical distributions accordingly. While high-resolution movement and environmental data provide improved predictability of microscale habitat use and distribution, other variables such as prey distribution, behavior, and competition would further improve habitat use models for this highly mobile species. [ABSTRACT FROM AUTHOR]

Juvenile white sharks (Carcharodon carcharias) typically aggregate along coastal beaches; however, high levels of recruitment and shifting oceanographic conditions may be causing habitat use expansions. Telemetry data indicate increased habitat use at the Northern Channel Islands (California, USA) by juvenile white shark that may be in response to increased population density at aggregation locations, or anomalous oceanographic events that impact habitat use or expand available habitat. Findings illustrate the need for long‐term movement monitoring and understanding drivers of habitat use shifts and expansion to improve ecosystem management. [ABSTRACT FROM AUTHOR]

We present results from the first 22 GHz space very long baseline interferometric (VLBI) imaging observations of M87 by RadioAstron. As a part of the Nearby AGN Key Science Program, the source was observed in 2014 February at 22 GHz with 21 ground stations, reaching projected (u, v) spacings up to ∼11 G λ. The imaging experiment was complemented by snapshot RadioAstron data of M87 obtained during 2013–2016 from the AGN Survey Key Science Program. Their longest baselines extend up to ∼25 G λ. For all of these measurements, fringes are detected only up to ∼2.8 Earth diameter or ∼3 G λ baseline lengths, resulting in a new image with angular resolution of ∼150 μ as or ∼20 Schwarzschild radii spatial resolution. The new image not only shows edge-brightened jet and counterjet structures down to submilliarcsecond scales but also clearly resolves the VLBI core region. While the overall size of the core is comparable to those reported in the literature, the ground-space fringe detection and slightly superresolved RadioAstron image suggest the presence of substructures in the nucleus, whose minimum brightness temperature exceeds T B , min ∼ 10 12 K. It is challenging to explain the origin of this record-high T B , min value for M87 by pure Doppler boosting effect with a simple conical jet geometry and known jet speed. Therefore, this can be evidence for more extreme Doppler boosting due to a blazar-like small jet viewing angle or highly efficient particle acceleration processes occurring already at the base of the outflow. [ABSTRACT FROM AUTHOR]

With the ripening of 3D printing technology and the discovery of a variety of printable materials, 3D‐printed vascular stents provide new treatment options for patients with angiocardiopathy. Bioresorbable stent not only combines the advantages of metallic stent and drug‐coated balloon, but also avoids the disadvantages of them. 3D printing is also an economical and efficient way to produce stents and makes it possible to construct complex structures. In this study, stents made from poly(l‐lactic acid) (PLLA), poly(ε‐caprolactone) (PCL) and poly(l‐lactide‐co‐caprolactone) (PLCL) were manufactured by 3D printing and evaluated for radial strength, crystallinity and molecular weight. PLCL copolymerized by different proportions of lactic acid and caprolactone showed different mechanical and degradation properties. This demonstrated the potential of 3D printing as a low‐cost and high throughput method for stent manufacturing. The PLLA and PLCL 95/5 stents had similar mechanical properties, whereas PLCL 85/15 and PCL stents both had relatively low radial strength. In general, PLCL 95/5 had a faster degradation rate than PLLA. These two materials were made into peripheral vascular bioresorbable scaffolds (BRS) and further studied by additional bench testing. PLCL 95/5 peripheral BRS had superior mechanical properties in terms of flexural/bending fatigue and compression resistance. [ABSTRACT FROM AUTHOR]

Stress urinary incontinence (SUI) impacts ~1/3 of women over age 50. Negative publicity around PP meshes used in pelvic prolapse repair drives the need for identifying alternative biomaterials for SUI repair. Our study evaluated in vivo response to collagen sling implanted in an ovine model. Electrocompacted collagen threads were filament wound as slings and crosslinked in genipin. Collagen slings were implanted suburethrally mimicking the transvaginal tape technique. Main study groups were: Collagen sling (n = 3, 6 months) and PP sling (n = 3, 6 months). Collagen sling was also tested at 3‐weeks (n = 1) to observe early‐stage tissue response and 1‐year (n = 2) to assess biomaterial longevity in a preliminary capacity. Collagen slings healed to a fibrous ligament texture at 6 months and maintained such texture to 1 year. Histological scoring indicated biocompatible responses to collagen slings with no adverse events. All study groups exhibited complete tissue ingrowth and interstitial de novo collagen deposition at all time points. Collagen threads induced orderly de novo collagen deposition that was aligned along long axes of threads. Tissue infiltrated collagen slings that were explanted at 6 and 12 months presented similar structural strength with native tissues such as vagina and fascia, and PP (Lynx) slings (p >.05). With the limitation of low number of animals per time point in hindsight, this preliminary study justifies evaluation of collagen slings in a larger sample size of animals, particularly to assess persistence of ligamentous tissue response over longer durations than 1‐year. [ABSTRACT FROM AUTHOR]

While the function of migration varies among species, environmental temperature is known to be one of the most important abiotic variables that drive animal migration; however, quantifying the thresholds and timing of the cues that influence a mass emigration is difficult, often due to lack of monitoring resolution, particularly for large, highly mobile species. We used acoustic telemetry tracking and high-resolution water temperature data over a relatively large spatial scale (5.5 km2) to identify and quantify a thermal threshold for mass emigration of juvenile white sharks. Sixteen tagged sharks were observed to initiate a search for warmer water within 10–12 hours of an upwelling event where water temperatures dropped below 14 °C. Eleven sharks traveled ~ 35 km away where they experienced similar cold temperatures before returning to the aggregation site within 24 hours. Five days following the upwelling event, most sharks emigrated from the site for the season. Quantifying movement patterns across different spatial and temporal scales is necessary to understand cues and thresholds influencing animal migration, which may be greatly affected by climate anomalies and climate change, resulting in potential impacts on the dynamics of local prey species, management, and conservation policy and practice. [ABSTRACT FROM AUTHOR]

A female scalloped hammerhead shark (Sphyrna lewini) conducted a species record deep dive to 1240 m in coastal‐pelagic waters off Hawaii Island. This extends the deepest known depth range of the species by over 200 m (650 ft) and highlights the question of the extent to which deep‐diving activity is mediated by physiological constraints, such as temperature and oxygen availability. [ABSTRACT FROM AUTHOR]

Background: Successful management of massive rotator cuff (RC) tendon tears represents a treatment challenge because of the limited intrinsic healing capacity of native tendons and the risk of repair failure. Biologic augmentation of massive RC tears utilizing scaffolds—capable of regenerating bulk tendon tissue to achieve a mechanically functional repair—represents an area of increasing clinical interest. Purpose: To investigate the histological and biomechanical outcomes after the use of a novel biologic scaffold fabricated from woven electrochemically aligned collagen (ELAC) threads as a suture-holding, fully load-bearing, defect-bridging scaffold with or without mesenchymal stem cells (MSCs) compared with direct repair in the treatment of critically sized RC defects using a rabbit model. Study Design: Controlled laboratory study. Methods: A total of 34 New Zealand White rabbits underwent iatrogenic creation of a critically sized defect (6 mm) in the infraspinatus tendon of 1 shoulder, with the contralateral shoulder utilized as an intact control. Specimens were divided into 4 groups: (1) gap—negative control without repair; (2) direct repair of the infraspinatus tendon—operative control; (3) tendon repair using ELAC; and (4) tendon repair using ELAC + MSCs. Repair outcomes were assessed at 6 months using micro–computed tomography, biomechanical testing, histology, and immunohistochemistry. Results: Specimens treated with ELAC demonstrated significantly less tendon retraction when compared with the direct repair group specimens (P =.014). ELAC + MSCs possessed comparable biomechanical strength (178 ± 50 N) to intact control shoulders (199 ± 35 N) (P =.554). Histological analyses demonstrated abundant, well-aligned de novo collagen around ELAC threads in both the ELAC and the ELAC + MSC shoulders, with ELAC + MSC specimens demonstrating increased ELAC resorption (7% vs 37%, respectively; P =.002). The presence of extracellular matrix components, collagen type I, and tenomodulin, indicating tendon-like tissue formation, was appreciated in both the ELAC and the ELAC + MSC groups. Conclusion: The application of MSCs to ELAC scaffolds improved biomechanical and histological outcomes when compared with direct repair for the treatment of critically sized defects of the RC in a rabbit model. Clinical Relevance: This study demonstrates the feasibility of repairing segmental tendon defects with a load-bearing, collagen biotextile in an animal model, showing the potential applicability of RC repair supplementation using allogeneic stem cells. [ABSTRACT FROM AUTHOR]

White sharks (Carcharodon carcharias) are the largest shark species to display regional endothermy. This capability likely facilitates exploitation of resources beyond thermal tolerance thresholds of potential sympatric competitors as well as sustained elevated swim speeds, but results in increased metabolic costs of adults, which has been documented in different studies. Little, however, is known of the metabolic requirements in free-swimming juveniles of the species, due to their large size at birth and challenges in measuring their oxygen consumption rates in captivity. We used trilateration of positional data from high resolution acoustic-telemetry to derive swim speeds from speed-over-ground calculations for eighteen free-swimming individual juvenile white sharks, and subsequently estimate associated mass-specific oxygen consumption rates as a proxy for field routine metabolic rates. Resulting estimates of mass-specific field routine metabolic rates (368 mg O2 kg−1 h−1 ± 27 mg O2 kg−1 h−1 [mean ± S.D.]) are markedly lower than those reported in sub-adult and adult white sharks by previous studies. We argue that median cruising speeds while aggregating at nearshore nursery habitats (0.6 m s-1 [mean ± S.E = 0.59 ± 0.001], 0.3 TL s-1) are likely a feature of behavioral strategies designed to optimize bioenergetic efficiency, by modulating activity rates in response to environmental temperature profiles to buffer heat loss and maintain homeostasis. Such behavioral strategies more closely resemble those exhibited in ectotherm sharks, than mature conspecifics. [ABSTRACT FROM AUTHOR]

Species occurrence records are vital data streams in marine conservation with a wide range of important applications. From 2001–2020, the Monterey Bay Aquarium led an international research collaboration to understand the life cycle, ecology, and behavior of white sharks (Carcharodon carcharias) in the southern California Current. The collaboration was devoted to tagging juveniles with animal-borne sensors, also known as biologging. Here we report the full data records from 59 pop-up archival (PAT) and 20 smart position and temperature transmitting (SPOT) tags that variously recorded pressure, temperature, and light-level data, and computed depth and geolocations for 63 individuals. Whether transmitted or from recovered devices, raw data files from successful deployments (n = 70) were auto-ingested from the manufacturer into the United States (US) Animal Telemetry Network's (ATN) Data Assembly Center (DAC). There they have attributed a full suite of metadata, visualized within their public-facing data portal, compiled for permanent archive under the DataONE Research Workspace member node, and are accessible for download from the ATN data portal. Measurement(s) animal migration, animal movements, environmental data Technology Type(s) biologging, telemetry tags, satellite transmitters Factor Type(s) depth • temperature • longitude • latitude Sample Characteristic - Organism Carcharodon carcharias Sample Characteristic - Environment ocean, nearshore marine environment, coastal aquatic habitat Sample Characteristic - Location State of Baja California • State of California • North East Pacific Ocean [ABSTRACT FROM AUTHOR]

As the fourth wave of the SARS-CoV-2 pandemic encircles the globe, there remains an urgent challenge to identify safe and effective treatment and prevention strategies that can be implemented in a range of health care and clinical settings. Substantial advances have been made in the use of anti-SARS-CoV-2 antibodies to mitigate the morbidity and mortality associated with COVID-19. On 15 June 2021, the National Institutes of Health, in collaboration with the U.S. Food and Drug Administration, convened a virtual summit to summarize existing knowledge on anti-SARS-CoV-2 antibodies and to identify key unanswered scientific questions to further catalyze the clinical development and implementation of antibodies. [ABSTRACT FROM AUTHOR]

The NIH Virtual SARS-CoV-2 Antiviral Summit, held on 6 November 2020, was organized to provide an overview on the status and challenges in developing antiviral therapeutics for coronavirus disease 2019 (COVID-19), including combinations of antivirals. Scientific experts from the public and private sectors convened virtually during a live videocast to discuss severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets for drug discovery as well as the preclinical tools needed to develop and evaluate effective small-molecule antivirals. The goals of the Summit were to review the current state of the science, identify unmet research needs, share insights and lessons learned from treating other infectious diseases, identify opportunities for public-private partnerships, and assist the research community in designing and developing antiviral therapeutics. This report includes an overview of therapeutic approaches, individual panel summaries, and a summary of the discussions and perspectives on the challenges ahead for antiviral development. [ABSTRACT FROM AUTHOR]

This paper presents the results from one of the first observations of ionospheric scintillation taken using the Low-Frequency Array (LOFAR). The observation was of the strong natural radio source Cassiopeia A, taken overnight on 18–19 August 2013, and exhibited moderately strong scattering effects in dynamic spectra of intensity received across an observing bandwidth of 10–80 MHz. Delay-Doppler spectra (the 2-D FFT of the dynamic spectrum) from the first hour of observation showed two discrete parabolic arcs, one with a steep curvature and the other shallow, which can be used to provide estimates of the distance to, and velocity of, the scattering plasma. A cross-correlation analysis of data received by the dense array of stations in the LOFAR "core" reveals two different velocities in the scintillation pattern: a primary velocity of ~20–40 ms−1 with a north-west to south-east direction, associated with the steep parabolic arc and a scattering altitude in the F-region or higher, and a secondary velocity of ~110 ms−1 with a north-east to south-west direction, associated with the shallow arc and a scattering altitude in the D-region. Geomagnetic activity was low in the mid-latitudes at the time, but a weak sub-storm at high latitudes reached its peak at the start of the observation. An analysis of Global Navigation Satellite Systems (GNSS) and ionosonde data from the time reveals a larger-scale travelling ionospheric disturbance (TID), possibly the result of the high-latitude activity, travelling in the north-west to south-east direction, and, simultaneously, a smaller-scale TID travelling in a north-east to south-west direction, which could be associated with atmospheric gravity wave activity. The LOFAR observation shows scattering from both TIDs, at different altitudes and propagating in different directions. To the best of our knowledge this is the first time that such a phenomenon has been reported. [ABSTRACT FROM AUTHOR]

Dextran-coated superparamagnetic iron oxide nanoparticles (Dex-SPIONs) are excellent magnetic resonance imaging contrast agents for disease diagnosis and therapy. They can be delivered to target tissues mainly though vascular endothelium cells, which are major targets of oxidative stress. In cardiovascular cells, autophagy serves primarily on a pro-survival approach that protects the cells from oxidative stress even some autophagy inducers have been developed for adjuvant therapy of cardiovascular disorders. Our study demonstrated that the nanoparticles could be taken up by human umbilical vein endothelial cells (HUVECs) without causing obvious cytotoxicity but triggering autophagy. Furthermore, our results revealed that Dex-SPIONs could enhance HUVECs survival and reverse the reduction of nitric oxide secretion under the condition of H2O2 damage. However, these effects could be diminished by the autophagy inhibitor. In particular, we discovered that Dex-SPIONs evoked autophagy in HUVECs by reducing the phosphorylation of PRAS40, an upstream regulator of autophagy initiation. These results suggested that Dex-SPIONs functions as an autophagic-related antioxidant in HUVECs which may be utilized as an adjuvant therapy to cardiovascular disease associated with oxidative stress. [ABSTRACT FROM AUTHOR]

Despite advancements in surgical techniques and materials for rotator cuff repair procedures, primary repair failures remain common. This study examines the use of electrochemically aligned collagen (ELAC) threads woven into biotextile scaffolds as grafts to repair critical infraspinatus tendon defects in New Zealand White rabbits. Three surgical treatment groups were evaluated: rabbits undergoing direct repair as operative controls, rabbits receiving ELAC scaffolds alone, and rabbits treated with mesenchymal stem cell (MSC)‐seeded ELAC scaffolds. In each animal, the intact, contralateral infraspinatus served as an internal positive control. Tendon–bone constructs were harvested after 3 months in vivo and outcome measures included biomechanical testing, histological staining, and immunohistochemical staining. Biomechanical testing revealed that maximum load‐bearing capacity was comparable between all groups, while MSC‐seeded scaffold repairs exhibited increased stiffness relative to non‐seeded scaffold repairs. Histological staining revealed robust collagen deposition around ELAC fibers and increased cellularity within the continuum of woven scaffolds as compared to native tendon. Immunohistochemical staining revealed presence of collagens I and III in all groups, but procollagen I and the tendon‐specific marker tenomodulin were only observed in seeded and non‐seeded ELAC scaffold repairs. Findings of this pilot study warrant continued investigation of ELAC biotextile scaffolds for repair of critically‐sized rotator cuff tendon defects. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1864–1876, 2019. [ABSTRACT FROM AUTHOR]

Dogfish sharks of the genus Squalus are small, deep-water sharks with a slow rate of molecular evolution that has led to their designation as a series of species complexes, with low between-species diversity relative to other taxa. The largest of these complexes is named for the Shortspine spurdog (Squalus mitsukurii Jordan & Snyder), a medium-sized dogfish shark common to warm upper slope and seamount habitats, with a putative circumglobal distribution that has come under investigation recently due to geographic variation in morphology and genetic diversity. The Hawaiian population of Squalus mitsukurii was examined using both morphological and molecular analyses, putting this group in an evolutionary context with animals from the type population in Japan and closely-related congeners. External morphology differs significantly between the Hawaiian and Japanese S. mitsukurii, especially in dorsal fin size and relative interdorsal length, and molecular analysis of 1,311 base pairs of the mitochondrial genes ND2 and COI show significant, species-level divergence on par with other taxonomic studies of this genus. The dogfish shark in Hawaii represents a new species in the genus, and the name Squalus hawaiiensis, the Hawaiian spurdog, is designated after the type location. [ABSTRACT FROM AUTHOR]

We performed Monte Carlo simulations of very-long-baseline interferometry (VLBI) observations of Earth-orbiting satellites incorporating co-located space-geodetic instruments in order to study how well the VLBI frame and the spacecraft frame can be tied using such measurements. We simulated observations of spacecraft by VLBI observations, time-of-flight (TOF) measurements using a time-encoded signal in the spacecraft transmission, similar in concept to precise point positioning, and differential VLBI (D-VLBI) observations using angularly nearby quasar calibrators to compare their relative performance. We used the proposed European Geodetic Reference Antenna in Space (E-GRASP) mission as an initial test case for our software. We found that the standard VLBI technique is limited, in part, by the present lack of knowledge of the absolute offset of VLBI time to Coordinated Universal Time at the level of microseconds. TOF measurements are better able to overcome this problem and provide frame ties with uncertainties in translation and scale nearly a factor of three smaller than those yielded from VLBI measurements. If the absolute time offset issue can be resolved by external means, the VLBI results can be significantly improved and can come close to providing 1 mm accuracy in the frame tie parameters. D-VLBI observations with optimum performance assumptions provide roughly a factor of two higher uncertainties for the E-GRASP orbit. We additionally simulated how station and spacecraft position offsets affect the frame tie performance. [ABSTRACT FROM AUTHOR]

Abstract: The redistribution of species has emerged as one of the most pervasive impacts of anthropogenic climate warming, and presents many societal challenges. Understanding how temperature regulates species distributions is particularly important for mobile marine fauna such as sharks given their seemingly rapid responses to warming, and the socio‐political implications of human encounters with some dangerous species. The predictability of species distributions can potentially be improved by accounting for temperature's influence on performance, an elusive relationship for most large animals. We combined multi‐decadal catch data and bio‐logging to show that coastal abundance and swimming performance of tiger sharks Galeocerdo cuvier are both highest at ~22°C, suggesting thermal constraints on performance may regulate this species' distribution. Tiger sharks are responsible for a large proportion of shark bites on humans, and a focus of controversial control measures in several countries. The combination of distribution and performance data moves towards a mechanistic understanding of tiger shark's thermal niche, and delivers a simple yet powerful indicator for predicting the location and timing of their occurrences throughout coastlines. For example, tiger sharks are mostly caught at Australia's popular New South Wales beaches (i.e. near Sydney) in the warmest months, but our data suggest similar abundances will occur in winter and summer if annual sea surface temperatures increase by a further 1–2°C. [ABSTRACT FROM AUTHOR]

Maintenance of epithelial tissue integrity requires coordination between cell-cell adherens junctions, tight junctions (TJ), and the perijunctional actomyosin cytoskeleton. Here we addressed the hypothesis that alterations in TJ structure and remodeling of the actomyosin cytoskeleton modify epithelial mechanics. Current methods to measure supracellular mechanical properties disrupt intact monolayers, therefore, we developed a novel method using noncontact acoustic frequency-modulation atomic force microscopy (FM-AFM) and tested it on MDCK polarized monolayers. Our results show that double knockdown (dKD) of ZO-1/ZO-2 elevates the apical epithelial tension and effective viscosity. Interestingly, epithelial tension is more sensitive to inhibition of myosin II ATPase activity than to inhibition of ROCK activity, but viscosity is highly sensitive to both. Additionally, we showed epithelial intercellular pulling forces at tricellular junctions and adhesion forces in dKD cells are elevated with an increase in contractility. In conclusion, FM-AFM enables the physiological and quantitative investigation of mechanics in intact epithelium. [ABSTRACT FROM AUTHOR]

SORBS2 is a scaffolding protein associated with Abl/Arg non-receptor tyrosine kinase pathways and is known to interact with actin and several other cytoskeletal proteins in various cell types. Previous BioID proximity labeling of tight and adherens junction proteins suggested that SORBS2 is a component of the apical junction complex of epithelial cells. We asked whether SORBS2 plays a previously unappreciated role in controlling perijunctional actin and tight junction barrier function. Using super resolution imaging we confirmed that SORBS2 is localized at the apical junction complex but farther from the membrane than ZO-1 and located partially overlapping both the tight- and adherens junctions with a periodic concentration that alternates with myosin IIB in polarized epithelial cells. Overexpression of GFP-SORBS2 recruited alpha-actinin, vinculin and N-WASP, and possibly CIP4 to cellular junctions. However, CRISPR-Cas9 knock-out of SORBS2 did not alter the localization- or immunofluorescent staining intensity of these or several other junctional- and cytoskeletal proteins. SORBS2 knock-out also did not affect the barrier function as measured by TER and dextran flux; nor did it change actin-dependent junction re-assembly as measured by Ca2+-switch and Latrunculin-B wash-out assays. The kinetics of HGF-induced cell scattering and wound healing, and dextran flux increase induced by PDGF also were unaffected by SORBS2 knock-out. SORBS2 concentrates with apical junctional actin that accumulates in response to knock-down of ZO-1 and ZO-2. In spite of our finding that SORBS2 is clearly a component of the apical junction complex, it does not appear to be required for either normal tight- or adherens junction assembly, structure or function or for growth factor-mediated changes in tight junction dynamics. [ABSTRACT FROM AUTHOR]

Background: While mesh reinforcement is recognized as the optimal strategy for many hernia repairs, there remains debate on the optimal position for deployment and characteristics that lead to improved biocompatibility. Coatings are an avenue by which integration may be improved. Our aim was to evaluate tissue integration between uncoated, fibroblast- and mesenchymal stem cell-coated meshes placed as subcutaneous onlay (ON) or intraperitoneal underlay (UN).Methods: Three commonly used biologic and synthetic hernia meshes were tested including Parietex, TIGR and Strattice. Each mesh was coated with rat kidney fibroblasts (NRKs) or rat mesenchymal stem cells (MSCs) along with an uncoated group. In the ON group, mesh was fixated on top of the external oblique fascia. In the UN group, mesh was placed against the intact peritoneum. Animals were survived for 30 days and killed for biomechanical and histologic analysis. A "T"-peel test was performed on a mesh-tissue explant from each sample to analyze the strength of integration at the mesh-tissue interface. Tissue integration was evaluated histologically using an established scoring system.Results: All uncoated meshes demonstrated significantly higher tissue ingrowth in the UN compared to ON position. Cell-coating of synthetic meshes decreased tissue ingrowth as UN, but increased it as ON, with a net effect of minimizing biomechanical difference between the two positions. In the biologic group however, NRK-coating decreased tissue ingrowth regardless of position, while MSC-coating increased it in both ON and UN positions.Conclusions: Both cell-coating and positioning affect mesh-tissue integration. Integration is superior in the underlay position compared to onlay when uncoated. Cell-coating of selected synthetic meshes can improve integration, particularly in the onlay position. Furthermore, MSCs appear to be a viable choice for biologic mesh coating, especially when implanted as an onlay. Overall, cell-coating of surgical meshes appears to a have a potential to improve mesh-tissue integration. [ABSTRACT FROM AUTHOR]

Despite their recognized limitations, bibliometric assessments of scientific productivity have been widely adopted. We describe here an improved method to quantify the influence of a research article by making novel use of its co-citation network to field-normalize the number of citations it has received. Article citation rates are divided by an expected citation rate that is derived from performance of articles in the same field and benchmarked to a peer comparison group. The resulting Relative Citation Ratio is article level and field independent and provides an alternative to the invalid practice of using journal impact factors to identify influential papers. To illustrate one application of our method, we analyzed 88,835 articles published between 2003 and 2010 and found that the National Institutes of Health awardees who authored those papers occupy relatively stable positions of influence across all disciplines. We demonstrate that the values generated by this method strongly correlate with the opinions of subject matter experts in biomedical research and suggest that the same approach should be generally applicable to articles published in all areas of science. A beta version of iCite, our web tool for calculating Relative Citation Ratios of articles listed in PubMed, is available at . [ABSTRACT FROM AUTHOR]

The article discusses a study related to the Relative Citation Ratio (RCR) that emerges objecting to the construction of both the numerator and denominator of the metric. It mentions addition of data on the stability of RCR values with reference to article citation rates of older articles. It also highlights analysis of the year-by-year changes in RCR values of articles funded by the U.S. National Institutes of Health (NIH).

ABSTRACT The effects of different material surfaces on phenotypic expression in macrophages and foreign body giant cells (FBGC) were addressed using our in vitro system of interleukin (IL)-4-induced macrophage fusion and FBGC formation. Arginine-glycine-aspartate (RGD)-, vitronectin (VN)-, and chitosan (CH)-adsorbed cell culture polystyrene, carboxylated (C, negatively charged) polystyrene, and unmodified (PS, non-cell culture treated) polystyrene were compared for their abilities to support monocyte/macrophage adhesion and IL-4-induced macrophage fusion. Pooled whole cell lysates from four different donors were evaluated by immunoblotting for expression of selected components in monocytes, macrophages, and FBGC. In addition to RGD and VN as previously shown, we find that CH supports macrophage adhesion and FBGC formation, whereas C or PS support macrophage adhesion but do not permit macrophage fusion under otherwise identical conditions of IL-4 stimulation. Likewise, components related to macrophage fusion (CD206, CD98, CD147, CD13) are strongly expressed on RGD-, VN-, and CH-adsorbed surfaces but are greatly diminished or not detected on C or PS. Importantly, material surfaces also influence the FBGC phenotype itself, as demonstrated by strong differences in patterns of expression of HLA-DR, B7-2, B7-H1, and toll-like receptor (TLR)-2 on RGD, VN, and CH despite morphologic similarities between FBGC on these surfaces. Likewise, we observe differences in the expression of B7-2, α2-macroglobulin, TLR-2, and fascin-1 between mononuclear macrophages on C and PS. Collectively, these findings reveal the extent to which material surface chemistry influences macrophage/FBGC phenotype beyond evident morphological similarities or differences and identify CH as an FBGC-supportive substrate. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1380-1390, 2015. [ABSTRACT FROM AUTHOR]

Tight junctions are complex membrane structures that regulate paracellular movement of material across epithelia and play a role in cell polarity, signaling and cytoskeletal organization. In order to expand knowledge of the tight junction proteome, we used biotin ligase (BioID) fused to occludin and claudin-4 to biotinylate their proximal proteins in cultured MDCK II epithelial cells. We then purified the biotinylated proteins on streptavidin resin and identified them by mass spectrometry. Proteins were ranked by relative abundance of recovery by mass spectrometry, placed in functional categories, and compared not only among the N- and C- termini of occludin and the N-terminus of claudin-4, but also with our published inventory of proteins proximal to the adherens junction protein E-cadherin and the tight junction protein ZO-1. When proteomic results were analyzed, the relative distribution among functional categories was similar between occludin and claudin-4 proximal proteins. Apart from already known tight junction- proteins, occludin and claudin-4 proximal proteins were enriched in signaling and trafficking proteins, especially endocytic trafficking proteins. However there were significant differences in the specific proteins comprising the functional categories near each of the tagging proteins, revealing spatial compartmentalization within the junction complex. Taken together, these results expand the inventory of known and unknown proteins at the tight junction to inform future studies of the organization and physiology of this complex structure. [ABSTRACT FROM AUTHOR]

A novel biofabrication modality, electrophoretic compaction with macromolecular alignment, is utilized to make collagen threads that mimic the native tendon's structure and mechanical properties. A device with kinematic electrodes is designed to fabricate collagen threads in continuous length. For the first time, a 3D-biotextile is woven purely from collagen. Mechanical properties and load-displacement behavior of the biotextile mimic those of the native tendon while presenting a porosity of 80%. The open pore network facilitates cell seeding across the continuum of the bioscaffold. Mesenchymal stem cells (MSCs) seeded in the woven scaffold undergo tenogenic differentiation in the absence of growth factors and synthesize a matrix that is positive for tenomodulin, COMP and type I collagen. Up-regulation of tenomodulin, a tendon specific marker, is 11.6 ± 3.5 fold, COMP is up-regulated 16.7 ± 5.5 fold, and Col I is up-regulated 6.9 ± 2.7 fold greater on ELAC threads when compared to randomly oriented collagen gels. These results demonstrate that a bioscaffold woven using collagen threads with densely compacted and anisotropically aligned substrate texture stimulates tenogenesis topographically, rendering the electrochemically aligned collagen as a promising candidate for functional repair of tendons and ligaments. [ABSTRACT FROM AUTHOR]

In previous studies that explored the influence of cytokines on foreign body giant cell (FBGC) formation, we focused on interleukin (IL)−4 and IL-13, each of which was discovered to induce macrophage fusion leading to FBGC formation in vitro. Two correlative in vivo studies also confirmed that IL-4 plays a role in FBGC formation on implanted biomaterials, but that T lymphocytes are not the source of IL-4 or other cytokines that support this process. The present study focused on identification of the cellular source of macrophage fusion-inducing cytokines, including natural killer (NK) or NKT lymphocytes and mast cells using mouse models genetically deficient in each of these cell types, as well as IL-4 receptor alpha(IL-4Rα)-deficient and severe combined immunodeficient (SCID) mice. Polyetherurethane (PEU) and polyethylene terephthalate (PET) polymers were subcutaneously implanted and retrieved after 14, 21, or 28 days. FBGC formation was evaluated using quantitative and qualitative data from retrieved polymer surfaces. Both types of data indicate that, compared to normal control mice, neither NK or NKT lymphocytes nor mast cells are required for FBGC formation. Furthermore, FBGC formation on biomaterials can proceed in IL-4Rα-deficient and in SCID mice. Similar conclusions were made regarding FBGC formation on both PEU and PET biomaterials. These data suggest that other sources of IL-4/IL-13 and/or additional macrophage fusion-inducing cytokines can mediate FBGC formation on implanted biomaterials, or that, in the absence of normal primary pathways, FBGC formation is nevertheless supported by redundant innate mechanisms. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2017-2023, 2014. [ABSTRACT FROM AUTHOR]

Coating of various synthetic, absorbable, and biologic meshes with mesenchymal stem cells (MSCs) and fibroblasts was analyzed qualitatively and quantitatively. Five hernia meshes-light weight monofilament polypropylene (Soft Mesh), polyester (Parietex-TET), polylactide composite (TIGR), heavy weight monofilament polypropylene (Marlex), and porcine dermal collagen (Strattice)-were coated with three cell lines: human dermal fibroblasts (HFs), rat kidney fibroblasts (NRKs), and rat MSCs. Cell densities were determined at different time points. Samples also underwent histology and transmission electron microscopic (TEM) analyses. It required HFs 3 weeks to cover the entire mesh, while only 2 weeks for NRKs and MSCs to do so. MSCs had no preference for any of the meshes and produced the highest cell densities on Parietex and TIGR. Substrate-preference accounted for the significantly lower fibroblast densities on TIGR than Parietex. Fibroblasts failed to coat Marlex. Strattice, which had the least surface area, generated comparable cell densities to Parietex. Both histology and TEM confirmed cell coating of mesh surface. Various prosthetics can be coated by certain cell strains. Both mesh composition and cell preference dramatically influence the coating process. This methodology provides foundation for novel avenues of modulation of host response to various modern synthetic and biologic meshes. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 797-805, 2014. [ABSTRACT FROM AUTHOR]

Tiger sharks (Galecerdo cuvier) are apex predators characterized by their broad diet, large size and rapid growth. Tiger shark maximum size is typically between 380 & 450 cm Total Length (TL), with a few individuals reaching 550 cm TL, but the maximum size of tiger sharks in Hawaii waters remains uncertain. A previous study suggested tiger sharks grow rather slowly in Hawaii compared to other regions, but this may have been an artifact of the method used to estimate growth (unvalidated vertebral ring counts) compounded by small sample size and narrow size range. Since 1993, the University of Hawaii has conducted a research program aimed at elucidating tiger shark biology, and to date 420 tiger sharks have been tagged and 50 recaptured. All recaptures were from Hawaii except a single shark recaptured off Isla Jacques Cousteau (24°13′17″N 109°52′14″W), in the southern Gulf of California (minimum distance between tag and recapture sites  =  approximately 5,000 km), after 366 days at liberty (DAL). We used these empirical mark-recapture data to estimate growth rates and maximum size for tiger sharks in Hawaii. We found that tiger sharks in Hawaii grow twice as fast as previously thought, on average reaching 340 cm TL by age 5, and attaining a maximum size of 403 cm TL. Our model indicates the fastest growing individuals attain 400 cm TL by age 5, and the largest reach a maximum size of 444 cm TL. The largest shark captured during our study was 464 cm TL but individuals >450 cm TL were extremely rare (0.005% of sharks captured). We conclude that tiger shark growth rates and maximum sizes in Hawaii are generally consistent with those in other regions, and hypothesize that a broad diet may help them to achieve this rapid growth by maximizing prey consumption rates. [ABSTRACT FROM AUTHOR]

Ecological and societal disruptions by modern climate change are critically determined by the time frame over which climates shift beyond historical analogues. Here we present a new index of the year when the projected mean climate of a given location moves to a state continuously outside the bounds of historical variability under alternative greenhouse gas emissions scenarios. Using 1860 to 2005 as the historical period, this index has a global mean of 2069 (±18 years s.d.) for near-surface air temperature under an emissions stabilization scenario and 2047 (±14 years s.d.) under a 'business-as-usual' scenario. Unprecedented climates will occur earliest in the tropics and among low-income countries, highlighting the vulnerability of global biodiversity and the limited governmental capacity to respond to the impacts of climate change. Our findings shed light on the urgency of mitigating greenhouse gas emissions if climates potentially harmful to biodiversity and society are to be prevented. [ABSTRACT FROM AUTHOR]

Tight junctions (TJs) regulate the paracellular movement of ions, macromolecules and immune cells across epithelia. Zonula occludens (ZO)-1 is a multi-domain polypeptide required for the assembly of TJs. MDCK II cells lacking ZO-1, and its homolog ZO-2, have three distinct phenotypes: reduced localization of occludin and some claudins to the TJs, increased epithelial permeability, and expansion of the apical actomyosin contractile array found at the apical junction complex (AJC). However, it is unclear exactly which ZO-1 binding domains are required to coordinate these activities. We addressed this question by examining the ability of ZO-1 domain-deletion transgenes to reverse the effects of ZO depletion. We found that the SH3 domain and the U5 motif are required to recruit ZO-1 to the AJC and that localization is a prerequisite for normal TJ and cytoskeletal organization. The PDZ2 domain is not required for localization of ZO-1 to the AJC, but is necessary to establish the characteristic continuous circumferential band of ZO-1, occludin and claudin-2. PDZ2 is also required to establish normal permeability, but is not required for normal cytoskeletal organization. Finally, our results demonstrate that PDZ1 is crucial for the normal organization of both the TJ and the AJC cytoskeleton. Our results establish that ZO-1 acts as a true scaffolding protein and that the coordinated activity of multiple domains is required for normal TJ structure and function. [ABSTRACT FROM AUTHOR]

Biomaterial-centered infections are initiated by adhesion of bacteria to an implant, followed by colonization and mature biofilm formation. Staphylococcus epidermidis is commonly identified as the cause of these device-centered infections. This study used an in vitro model to evaluate temporal changes in the expression of genes- icaADBC, agrBDCA, aap, and atle-that have been identified to play a role in the pathogenesis of S. epidermidis infections. Real-time reverse transcription-polymerase chain reaction was used to determine changes in gene expression from S epidermidis biofilm grown on polyurethanes (Elasthane 80A, hydrophobic) modified with polyethylene oxide (Elasthane 80A-6PEO, hydrophilic) and fluorocarbon (Elasthane 80A-6F, hydrophobic). In vitro expression of the ica locus, which is involved in initial adhesion and intracellular aggregation, increased up to 100-fold from 2 to 48 h, whereas gene expression for autolysin AtlE decreased slightly from 2 to 12 h, followed by a 10-fold increase by 48 h. Upregulation of the aap gene associated with bacterial accumulation and the agr quorum-sensing system was observed during biofilm formation over 48 h. In addition, no correlation was observed between S. epidermidis gene expression and biomaterial surface chemistry. This study used an in vitro model to demonstrate that enhanced expression of the atle, aap, agr, and ica genes plays an important role in initial foreign body colonization and potentially in the establishment of a device-associated infection. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:2863-2869, 2012. [ABSTRACT FROM AUTHOR]

Claudins are critical components of epithelial and endothelial tight junction seals, but their post-transcriptional regulation remains poorly understood. Several studies have implicated phosphorylation in control of claudin localisation and/or function, but these have focused on single sites or pathways with differing results, so that it has been difficult to draw general functional conclusions. In this study, we used mass spectrometry (MS) analysis of purified claudin-2 from MDCK II cells and found that the cytoplasmic tail is multiply phosphorylated on serines, a threonine and tyrosines. Phos-tag SDS PAGE revealed that one site, S208, is heavily constitutively phosphorylated in MDCK II cells and in mouse kidney; this site was targeted for further study. Mutational analysis revealed that the phosphomimetic mutant of claudin-2, S208E, was preferentially localised to the plasma membrane while claudin-2 S208A, which could not be phosphorylated at this site, both immunolocalized and co-fractionated with lysosomal markers. Mutations at sites that were previously reported to interfere with plasma membrane targeting of claudin-2 reduced phosphorylation at S208, suggesting that membrane localisation is required for phosphorylation; however phosphorylation at S208 did not affect binding to ZO-1 or ZO-2 Administration of forskolin or PGE2 resulted in dephosphorylation at S208 and transient small increases in transepithelial electrical resistance (TER). Together these data are consistent with phosphorylation at S208 playing a major role in the retention of claudin-2 at the plasma membrane. [ABSTRACT FROM AUTHOR]