Synthesis and Characterization of 2-Decenoic Acid Modified Chitosan for Infection Prevention and Tissue Engineering

Chitosan nanofiber membranes are recognized as functional antimicrobial materials, as they can effectively provide a barrier that guides tissue growth and supports healing. Methods to stabilize nanofibers in aqueous solutions include acylation with fatty acids. Modification with fatty acids that also have antimicrobial and biofilm-resistant properties may be particularly beneficial in tissue regeneration applications. This study investigated the ability to customize the fatty acid attachment by acyl chlorides to include antimicrobial 2-decenoic acid. Synthesis of 2-decenoyl chloride was followed by acylation of electrospun chitosan membranes in pyridine. Physicochemical properties were characterized through scanning electron microscopy, FTIR, contact angle, and thermogravimetric analysis. The ability of membranes to resist biofilm formation by S. aureus and P. aeruginosa was evaluated by direct inoculation. Cytocompatibility was evaluated by adding membranes to cultures of NIH3T3 fibroblast cells. Acylation with chlorides stabilized nanofibers in aqueous media without significant swelling of fibers and increased hydrophobicity of the membranes. Acyl-modified membranes reduced both S. aureus and P. aeruginosa bacterial biofilm formation on membrane while also supporting fibroblast growth. Acylated chitosan membranes may be useful as wound dressings, guided regeneration scaffolds, local drug delivery, or filtration.     

Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis. After removal, these costimulatory ligands are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via CD28. Acquisition of CD86 from antigen-presenting cells is stimulated by T cell receptor engagement and observed in vitro and in vivo. These data reveal a mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands, accounting for many of the known features of the CD28-CTLA-4 system.     

Conserved structure for single-stranded telomeric DNA recognition

The essential Cdc13 protein in the yeast Saccharomyces cerevisiae is a single-stranded telomeric DNA binding protein required for chromosome end protection and telomere replication. Here we report the solution structure of the Cdc13 DNA binding domain in complex with telomeric DNA. The structure reveals the use of a single OB (oligonucleotide/oligosaccharide binding) fold augmented by an unusually large loop for DNA recognition. This OB fold is structurally similar to OB folds found in the ciliated protozoan telomere end-binding protein, although no sequence similarity is apparent between them. The common usage of an OB fold for telomeric DNA interaction demonstrates conservation of end-protection mechanisms among eukaryotes.     

Domoic Acid Improves the Competitive Ability of Pseudo-nitzschia delicatissima against the Diatom Skeletonema marinoi

Because domoic acid, a neurotoxic secondary metabolite produced by marine diatoms in the genus Pseudo-nitzschia, is hypothesized to be part of a high affinity iron uptake system, we investigated whether domoic acid could improve the competitive ability of Pseudo-nitzschia delicatissima, and whether the availability of iron changed the outcome of competition experiments. We found that domoic acid had a slight negative effect on growth of the diatom Skeletonema marinoi when it was grown in monocultures. However, when S. marinoi was cultured with P. delicatissima the presence of domoic acid resulted in a reduction of S. marinoi cells by up to 38% and an increase in P. delicatissima cell numbers by up to 17% under iron replete conditions. Similar effects were not observed in low iron treatments. Domoic acid was not taken up by P. delicatissima cells. Overall, our results indicate that domoic acid can improve the competitive ability of Pseudo-nitzschia spp. and that iron is likely to be involved. This study provides an unusual example of indirect inhibition of competitor growth mediated by a secondary metabolite.     

Diviner Lunar Radiometer observations of cold traps in the Moon's south polar region

Diviner Lunar Radiometer Experiment surface-temperature maps reveal the existence of widespread surface and near-surface cryogenic regions that extend beyond the boundaries of persistent shadow. The Lunar Crater Observation and Sensing Satellite (LCROSS) struck one of the coldest of these regions, where subsurface temperatures are estimated to be 38 kelvin. Large areas of the lunar polar regions are currently cold enough to cold-trap water ice as well as a range of both more volatile and less volatile species. The diverse mixture of water and high-volatility compounds detected in the LCROSS ejecta plume is strong evidence for the impact delivery and cold-trapping of volatiles derived from primitive outer solar system bodies.     

Main stem movement of Atlantic salmon parr in response to high river temperature

Atlantic salmon become thermally stressed when water temperatures exceed 23 °C. To alleviate this stress, they behaviourally thermoregulate by moving to patches of cold water, often forming large aggregations. These patches are known as thermal refuges. Given the consensus that climate change will increase temperatures in Atlantic salmon catchments, thermal refuges will become increasingly important in minimising summer mortalities. While the behaviour of salmonids within thermal refuges is fairly well understood, less is known about their main stem movement in search of thermal refuges or its thermal and temporal cues. We detail the results of a PIT telemetry study to investigate the main stem movement behaviour of thermally stressed Atlantic salmon parr in a temperature‐impacted river. PIT antennas placed around two thermal refuges and at the upstream and downstream limits of their surrounding reach were used to record the movement of salmonids during a heatwave. We observed parr movement at the upstream and downstream antennas 135 min prior to the occurrence of the midpoint of aggregations in the thermal refuges, indicating that Atlantic salmon parr make reach‐scale movements in search of cool water prior to aggregating. Logistic regression showed that the number of degree hours >28 °C predicted the occurrence of main stem movement with a good degree of accuracy, indicating that this temperature represents a fundamental threshold causing Atlantic salmon parr to move towards cool water. Such data could be instrumental in allowing river managers to place limits on human activity within rivers, allowing salmon populations time to recover following heat stress events.     

Comparing the behavioural thermoregulation response to heat stress by Atlantic salmon parr (Salmo salar) in two rivers

Climate change is expected to increase the frequency and magnitude of extreme thermal events in rivers. The Little Southwest Miramichi River (LSWM) and the Ouelle River (OR) are two Atlantic salmon (Salmo salar) rivers located in eastern Canada, where in recent years, water temperatures have exceeded known thermal limits (~23°C). Once temperature surpasses this threshold, juvenile salmon exploit thermal heterogeneity to behaviourally thermoregulate, forming aggregations in coolwater refuges. This study aimed to determine whether the behavioural thermoregulation response is universal across rivers, arising from common thermal cues. We detailed the temperature and discharge patterns of two geographically distinct rivers from 2010 to 2012 and compared these with aggregation onset temperature. PIT telemetry and snorkelling were used to confirm the presence of aggregations. Mean daily maximum temperature in 2010 was significantly greater in the OR versus the LSWM (p = 0.005), but not in other years (p = 0.090–0.353). Aggregations occurred on 14 and 9 occasions in the OR and LSWM respectively. Temperature at onset of aggregation was significantly greater in the OR (T_onset = 28.3°C) than in the LSWM (T_onset = 27.3°C; p = 0.049). Logistic regression models varied by river and were able to predict the probability of aggregation based on the preceding number of hours >23°C (R² = 0.61 & 0.65; P₅₀ = 27.4°C & 28.9°C; in the OR and LSWM respectively). These results imply the preceding local thermal regime may influence behaviour and indicate a degree of phenotypic plasticity, illustrating a need for localised management strategies.     

Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases

The Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 are critical signaling regulators in mammalian cells. The deletion of both Rac1 and Rac2 murine alleles leads to a massive egress of hematopoietic stem/progenitor cells (HSC/Ps) into the blood from the marrow, whereas Rac1-/- but not Rac2-/- HSC/Ps fail to engraft in the bone marrow of irradiated recipient mice. In contrast, Rac2, but not Rac1, regulates superoxide production and directed migration in neutrophils, and in each cell type, the two GTPases play distinct roles in actin organization, cell survival, and proliferation. Thus, Rac1 and Rac2 regulate unique aspects of hematopoietic development and function.