We report for the first time the ingestion of microplastics by scleractinian corals, and the presence of microplastics in coral reef waters adjacent to inshore reefs on Australia’s Great Barrier Reef ...(GRE, 18°31′S 146°23′E). Analysis of samples from sub-surface plankton tows conducted in close proximity to inshore reefs on the central GBR revealed microplastics, similar to those used in marine paints and fishing floats, were present in low concentrations at all water sampling locations. Experimental feeding trials revealed that corals mistake microplastics for prey and can consume up to ~50 μg plastic cm
−2
h
−1
, rates similar to their consumption of plankton and
Artemia
nauplii in experimental feeding assays. Ingested microplastics were found wrapped in mesenterial tissue within the coral gut cavity, suggesting that ingestion of high concentrations of microplastic debris could potentially impair the health of corals.
Cyclones are a poorly described disturbance in tropical lakes, with the potential to alter ecosystems and compromise the services they provide. In November 2020, Hurricanes Eta and Iota made landfall ...near the Nicaragua-Honduras border, inundating the region with a large amount of late-season precipitation. To understand the impact of these storms on Lake Yojoa, Honduras, we compared 2020 and 2021 conditions using continuous (every 16 days) data collected from five pelagic locations. The storms resulted in increased Secchi depth and decreased algal abundance in December 2020, and January and February 2021, and lower-than-average accumulation of hypolimnetic nutrients from the onset of stratification (April 2021) until mixus in November 2021. Despite the reduced hypolimnetic nutrient concentrations, epilimnetic nutrient concentrations returned to (and in some cases exceeded) pre-hurricane levels following annual water column turnover in 2021. This response suggests that Lake Yojoa's trophic state had only an ephemeral response to the disturbance imposed by the two hurricanes, likely due to internal input of sediment derived nutrients. These aseasonal storms acted as a large-scale experiment that resulted in nutrient dilution and demonstrated the resilience of Lake Yojoa's trophic state to temporary nutrient reductions.
Increasing demographic diversity is undoubtedly important and can aid in debiasing decision makers. Yet, the promises of demographic diversity are not always realized due to social integration ...problems. We consider why and for whom differences combined with homogeneity make a difference for groups in terms of integratively complex thinking and ideological decision making. Although research has shown that decision makers often rely on political biases, that work has not addressed when and why decision-making groups are able to overcome these biases-a pervasive concern in today's politically polarized social milieu. Drawing on the common in-group identity model and research on integrative complexity, we theorize that demographic diversity ultimately yields less ideological decision making because it prompts integrative complexity; however, demographic diversity only accrues this benefit in the presence of ideological homogeneity. We also reason that the relationship between integrative complexity and reduced ideological decision making emerges for more conservative (versus more liberal) groups. We find support for our expectations using a natural experiment of judges on the U.S. Courts of Appeals. Supplemental analyses indicate that working within a demographically diverse and ideologically homogeneous group also positively predicts integrative complexity in future decision-making groups. Finally, we find that demographic and ideological diversity can substitute for one another, but no additional integrative complexity benefits accrue when both are present. We discuss implications of this research in light of the ongoing conversation about the value of diversity and today's polarized political climate.
Effective delivery of protein therapeutics to the central nervous system (CNS) has been greatly restricted by the blood-brain barrier (BBB). We describe the development of a BBB transport vehicle ...(TV) comprising an engineered Fc fragment that exploits receptor-mediated transcytosis for CNS delivery of biotherapeutics by binding a highly expressed brain endothelial cell target. TVs were engineered using directed evolution to bind the apical domain of the human transferrin receptor (hTfR) without the use of amino acid insertions, deletions, or unnatural appendages. A crystal structure of the TV-TfR complex revealed the TV binding site to be away from transferrin and FcRn binding sites, which was further confirmed experimentally in vitro and in vivo. Recombinant expression of TVs fused to anti-β-secretase (BACE1) Fabs yielded antibody transport vehicle (ATV) molecules with native immunoglobulin G (IgG) structure and stability. Peripheral administration of anti-BACE1 ATVs to hTfR-engineered mice and cynomolgus monkeys resulted in substantially improved CNS uptake and sustained pharmacodynamic responses. The TV platform readily accommodates numerous additional configurations, including bispecific antibodies and protein fusions, yielding a highly modular CNS delivery platform.
Sustained muscle contraction occurs through interactions between actin and myosin filaments within sarcomeres and requires a constant supply of adenosine triphosphate (ATP) from nearby mitochondria. ...However, it remains unclear how different physical configurations between sarcomeres and mitochondria alter the energetic support for contractile function. Here, we show that sarcomere cross-sectional area (CSA) varies along its length in a cell type-dependent manner where the reduction in Z-disk CSA relative to the sarcomere center is closely coordinated with mitochondrial network configuration in flies, mice, and humans. Further, we find myosin filaments near the sarcomere periphery are curved relative to interior filaments with greater curvature for filaments near mitochondria compared to sarcoplasmic reticulum. Finally, we demonstrate variable myosin filament lattice spacing between filament ends and filament centers in a cell type-dependent manner. These data suggest both sarcomere structure and myofilament interactions are influenced by the location and orientation of mitochondria within muscle cells.
Nearly all freshwaters and coastal zones of the US are degraded from inputs of excess reactive nitrogen (Nr), sources of which are runoff, atmospheric N deposition, and imported food and feed. Some ...major adverse effects include harmful algal blooms, hypoxia of fresh and coastal waters, ocean acidification, long-term harm to human health, and increased emissions of greenhouse gases. Nitrogen fluxes to coastal areas and emissions of nitrous oxide from waters have increased in response to N inputs. Denitrification and sedimentation of organic N to sediments are important processes that divert N from downstream transport. Aquatic ecosystems are particularly important denitrification hotspots. Carbon storage in sediments is enhanced by Nr, but whether carbon is permanently buried is unknown. The effect of climate change on N transport and processing in fresh and coastal waters will be felt most strongly through changes to the hydrologic cycle, whereas N loading is mostly climate-independent. Alterations in precipitation amount and dynamics will alter runoff, thereby influencing both rates of Nr inputs to aquatic ecosystems and groundwater and the water residence times that affect Nr removal within aquatic systems. Both infrastructure and climate change alter the landscape connectivity and hydrologic residence time that are essential to denitrification. While Nr inputs to and removal rates from aquatic systems are influenced by climate and management, reduction of N inputs from their source will be the most effective means to prevent or to minimize environmental and economic impacts of excess Nr to the nation’s water resources.
Over the last decade, the United States has seen increasing antidemocratic rhetoric by political leaders. Yet, prior work suggests that such norm-violating rhetoric does not undermine support for ...democracy as a system of government. We argue that, while that may be true, such rhetoric does vitiate support for specific democratic principles. We test this theory by extending prior work to assess the effects of Trump’s norm-violating rhetoric on general support for democracy as well as for the principles of participatory inclusiveness, contestation, the rule of law, and political equality. We find that Trump’s rhetoric does not alter attitudes toward democracy as a preferred system but does reduce support for inclusiveness and equality among his supporters. Our findings suggest that elite rhetoric can undermine basic principles of American democracy.
Abstract
Microglia are activated after spinal cord injury (SCI), but their phagocytic mechanisms and link to neuroprotection remain incompletely characterized. Docosahexaenoic acid (DHA) has been ...shown to have significant neuroprotective effects after hemisection and compression SCI and can directly affect microglia in these injury models. In rodent contusion SCI, we demonstrate that DHA (500 nmol/kg) administered acutely post-injury confers neuroprotection and enhances locomotor recovery, and also exerts a complex modulation of the microglial response to injury. In rodents, at 7 days after SCI, the level of phagocytosed myelin within Iba1-positive or P2Y12-positive cells was significantly lower after DHA treatment, and this occurred in parallel with an increase in intracellular miR-124 expression. Furthermore, intraspinal administration of a miR-124 inhibitor significantly reduced the DHA-induced decrease in myelin phagocytosis in mice at 7 days post-SCI. In rat spinal primary microglia cultures, DHA reduced the phagocytic response to myelin, which was associated with an increase in miR-124, but not miR-155. A similar response was observed in a microglia cell line (BV2) treated with DHA, and the effect was blocked by a miR-124 inhibitor. Furthermore, the phagocytic response of BV2 cells to stressed neurones was also reduced in the presence of DHA. In peripheral monocyte-derived macrophages, the expression of the M1, but not the M0 or M2 phenotype, was reduced by DHA, but the phagocytic activation was not altered. These findings show that DHA induces neuroprotection in contusion injury. Furthermore, the improved outcome is via a miR-124-dependent reduction in the phagocytic response of microglia.
Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair ...defects would respond to poly(adenosine diphosphate ADP-ribose) polymerase (PARP) inhibition with olaparib.
We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. The primary end point was the response rate, defined either as an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1, or as a reduction of at least 50% in the prostate-specific antigen level or a confirmed reduction in the circulating tumor-cell count from 5 or more cells per 7.5 ml of blood to less than 5 cells per 7.5 ml. Targeted next-generation sequencing, exome and transcriptome analysis, and digital polymerase-chain-reaction testing were performed on samples from mandated tumor biopsies.
Overall, 50 patients were enrolled; all had received prior treatment with docetaxel, 49 (98%) had received abiraterone or enzalutamide, and 29 (58%) had received cabazitaxel. Sixteen of 49 patients who could be evaluated had a response (33%; 95% confidence interval, 20 to 48), with 12 patients receiving the study treatment for more than 6 months. Next-generation sequencing identified homozygous deletions, deleterious mutations, or both in DNA-repair genes--including BRCA1/2, ATM, Fanconi's anemia genes, and CHEK2--in 16 of 49 patients who could be evaluated (33%). Of these 16 patients, 14 (88%) had a response to olaparib, including all 7 patients with BRCA2 loss (4 with biallelic somatic loss, and 3 with germline mutations) and 4 of 5 with ATM aberrations. The specificity of the biomarker suite was 94%. Anemia (in 10 of the 50 patients 20%) and fatigue (in 6 12%) were the most common grade 3 or 4 adverse events, findings that are consistent with previous studies of olaparib.
Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate. (Funded by Cancer Research UK and others; ClinicalTrials.gov number, NCT01682772; Cancer Research UK number, CRUK/11/029.).
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