Feeding ecology of broadbill swordfish (Xiphias gladius) in the California current

Funding: Support for our study includes salary funding from the NOAA Fisheries’ Office of Science and Technology and contract funds from the Cooperative Institute for Marine, Earth, and Atmospheric Systems. The National Observer Program within NOAA Fisheries’ Office of Science and Technology carried out sample collection. While the study fits the scope of work under the coauthors’ performance plans, they received no specific funding for this work. The funders had no role in study design, analysis, decision to publish, or preparation of the manuscript. Acknowledgments This work would not have been possible without the assistance and samples provided by the NMFS Southwest Region Fishery Observer Program and the participating drift gillnet fishermen. We thank several assistant volunteers who helped process the stomach samples. Alexandra Stohs provided research assistance. Mark Lowry, Eric Hochberg and John Hyde helped identify some prey specimens. John Field, Chugey Sepulveda and Scott Aalbers offered science feedback. Barbara Muhling helped create the map. Kristen Koch, Annie Yau, Brad Erisman, Heidi Dewar, Stephanie Flores, Crystal Dombrow, Elan Portner and Ruben Bergtraun provided useful comments on the draft. Debra Losey assisted with library research. We also thank Hiroshi Ohizumi and two anonymous reviewers for their careful critiques that helped improve the manuscript.Peer reviewedPublisher PD

Mutational analysis of the transferrin receptor reveals overlapping HFE and transferrin binding sites

The transferrin receptor (TfR) binds two proteins critical for iron metabolism: transferrin (Tf) and HFE, the protein mutated in hereditary hemochromatosis. Previous results demonstrated that Tf and HFE compete for binding to TfR, suggesting that Tf and HFE bind to the same or an overlapping site on TfR. TfR is a homodimer that binds one Tf per polypeptide chain (2:2, TfR/Tf stoichiometry), whereas both 2:1 and 2:2 TfR/HFE stoichiometries have been observed. In order to more fully characterize the interaction between HFE and TfR, we determined the binding stoichiometry using equilibrium gel-filtration and analytical ultracentrifugation. Both techniques indicate that a 2:2 TfR/HFE complex can form at submicromolar concentrations in solution, consistent with the hypothesis that HFE competes for Tf binding to TfR by blocking the Tf binding site rather than by exerting an allosteric effect. To determine whether the Tf and HFE binding sites on TfR overlap, residues at the HFE binding site on TfR were identified from the 2.8 Å resolution HFE-TfR co-crystal structure, then mutated and tested for their effects on HFE and Tf binding. The binding affinities of soluble TfR mutants for HFE and Tf were determined using a surface plasmon resonance assay. Substitutions of five TfR residues at the HFE binding site (L619A, R629A, Y643A, G647A and F650Q) resulted in significant reductions in Tf binding affinity. The findings that both HFE and Tf form 2:2 complexes with TfR and that mutations at the HFE binding site affect Tf binding support a model in which HFE and Tf compete for overlapping binding sites on TfR

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Condensed-Phase Photochemistry in the Absence of Radiation Chemistry

We report post-irradiation photochemistry studies of condensed ammonia using photons of energies below condensed ammonia’s ionization threshold of ~ 9 eV. Hydrazine (N2H4), diazene (also known as diimide and diimine) (N2H2), triazane (N3H5), and one or more isomers of N3H3 are detected as photochemistry products during temperature-programmed desorption. Product yields increase monotonically with (1) photon fluence and (2) film thickness. In the studies reported herein, the energies of photons responsible for product formation are constrained to less than 7.4 eV. Previous post-irradiation photochemistry studies of condensed ammonia employed photons sufficiently energetic to ionize condensed ammonia and initiate radiation chemistry. Such studies typically involve ion-molecule reactions and electron-induced reactions in addition to photochemistry. Although photochemistry is cited as a dominant mechanism for the synthesis of prebiotic molecules in interstellar ices, to the best of our knowledge, ours is one of the first astrochemically-relevant studies that has found unambiguous evidence for condensed-phase chemical synthesis induced by photons in the absence of ionization

Age-dependent effects of low-dose nicotine treatment on cocaine-induced behavioral plasticity in rats

Epidemiological evidence of early adolescent tobacco use, prior to that of marijuana and other illicit drugs, has led to the hypothesis that nicotine is a “gateway” drug that sensitizes reward pathways to the addictive effects of other psychostimulants. To test this hypothesis, we have compared the effect of a brief, low-dose nicotine pretreatment of adolescent and adult rats on subsequent locomotor response to acute and chronic cocaine. Adolescents, aged postnatal day (P) 28, and adults, aged P86, were given four daily injections of saline or nicotine (0.06 mg/kg, i.v.). At P32 and P90, rats were given acute injections of cocaine (0, 0.4 or 1.0 mg/kg, i.v.) and monitored for locomotor activity in either a habituated or novel test environment. To examine cocaine sensitization, rats were treated for 3 days with saline or cocaine (0.4 mg/kg, i.v.), and, after 1 day of withdrawal, were given a challenge dose of cocaine (0.4 mg/kg, i.v.). Nicotine pretreatment did not affect acute, drug-induced locomotor activity at either age. However, age differences in cocaine response were observed, with adolescent animals showing enhanced locomotor activity in the novel environment. Adolescent controls did not exhibit cocaine-induced locomotor sensitization, whereas adults did. Nicotine pretreatment during adolescence promoted the development and expression of a sensitized response to repeated cocaine exposure similar to that observed in saline-pretreated adult controls. These findings show that brief pretreatment with nicotine, in a low dose comparable to that inhaled in 2–4 cigarettes, enhances cocaine-induced behavioral plasticity in adolescent rats

Identifying anomalous radio sources in the Evolutionary Map of the Universe Pilot Survey using a complexity-based approach

The Evolutionary Map of the Universe (EMU) large-area radio continuum survey will detect tens of millions of radio galaxies, giving an opportunity for the detection of previously unknown classes of objects. To maximize the scientific value and make new discoveries, the analysis of these data will need to go beyond simple visual inspection. We propose the coarse-grained complexity, a simple scalar quantity relating to the minimum description length of an image that can be used to identify unusual structures. The complexity can be computed without reference to the broader sample or existing catalogue data, making the computation efficient on new surveys at very large scales (such as the full EMU survey). We apply our coarse-grained complexity measure to data from the EMU Pilot Survey to detect and confirm anomalous objects in this data set and produce an anomaly catalogue. Rather than work with existing catalogue data using a specific source detection algorithm, we perform a blind scan of the area, computing the complexity using a sliding square aperture. The effectiveness of the complexity measure for identifying anomalous objects is evaluated using crowd-sourced labels generated via the Zooniverse.org platform. We find that the complexity scan identifies unusual sources, such as odd radio circles, by partitioning on complexity. We achieve partitions where 5 per cent of the data is estimated to be 86 per cent complete, and 0.5 per cent is estimated to be 94 per cent pure, with respect to anomalies and use this to produce an anomaly catalogue

Hypoxia-Induced Retinal Angiogenesis in Zebrafish as a Model to Study Retinopathy

Mechanistic understanding and defining novel therapeutic targets of diabetic retinopathy and age-related macular degeneration (AMD) have been hampered by a lack of appropriate adult animal models. Here we describe a simple and highly reproducible adult fli-EGFP transgenic zebrafish model to study retinal angiogenesis. The retinal vasculature in the adult zebrafish is highly organized and hypoxia-induced neovascularization occurs in a predictable area of capillary plexuses. New retinal vessels and vascular sprouts can be accurately measured and quantified. Orally active anti-VEGF agents including sunitinib and ZM323881 effectively block hypoxia-induced retinal neovascularization. Intriguingly, blockage of the Notch signaling pathway by the inhibitor DAPT under hypoxia, results in a high density of arterial sprouting in all optical arteries. The Notch suppression-induced arterial sprouting is dependent on tissue hypoxia. However, in the presence of DAPT substantial endothelial tip cell formation was detected only in optic capillary plexuses under normoxia. These findings suggest that hypoxia shifts the vascular targets of Notch inhibitors. Our findings for the first time show a clinically relevant retinal angiogenesis model in adult zebrafish, which might serve as a platform for studying mechanisms of retinal angiogenesis, for defining novel therapeutic targets, and for screening of novel antiangiogenic drugs

Passive and Motivated Perception of Emotional Faces: Qualitative and Quantitative Changes in the Face Processing Network

Emotionally expressive faces are processed by a distributed network of interacting sub-cortical and cortical brain regions. The components of this network have been identified and described in large part by the stimulus properties to which they are sensitive, but as face processing research matures interest has broadened to also probe dynamic interactions between these regions and top-down influences such as task demand and context. While some research has tested the robustness of affective face processing by restricting available attentional resources, it is not known whether face network processing can be augmented by increased motivation to attend to affective face stimuli. Short videos of people expressing emotions were presented to healthy participants during functional magnetic resonance imaging. Motivation to attend to the videos was manipulated by providing an incentive for improved recall performance. During the motivated condition, there was greater coherence among nodes of the face processing network, more widespread correlation between signal intensity and performance, and selective signal increases in a task-relevant subset of face processing regions, including the posterior superior temporal sulcus and right amygdala. In addition, an unexpected task-related laterality effect was seen in the amygdala. These findings provide strong evidence that motivation augmentsco-activity among nodes of the face processing network and the impact of neural activity on performance. These within-subject effects highlight the necessity to consider motivation when interpreting neural function in special populations, and to further explore the effect of task demands on face processing in healthy brains

Tipping the Balance: Robustness of Tip Cell Selection, Migration and Fusion in Angiogenesis

Vascular abnormalities contribute to many diseases such as cancer and diabetic retinopathy. In angiogenesis new blood vessels, headed by a migrating tip cell, sprout from pre-existing vessels in response to signals, e.g., vascular endothelial growth factor (VEGF). Tip cells meet and fuse (anastomosis) to form blood-flow supporting loops. Tip cell selection is achieved by Dll4-Notch mediated lateral inhibition resulting, under normal conditions, in an interleaved arrangement of tip and non-migrating stalk cells. Previously, we showed that the increased VEGF levels found in many diseases can cause the delayed negative feedback of lateral inhibition to produce abnormal oscillations of tip/stalk cell fates. Here we describe the development and implementation of a novel physics-based hierarchical agent model, tightly coupled to in vivo data, to explore the system dynamics as perpetual lateral inhibition combines with tip cell migration and fusion. We explore the tipping point between normal and abnormal sprouting as VEGF increases. A novel filopodia-adhesion driven migration mechanism is presented and validated against in vivo data. Due to the unique feature of ongoing lateral inhibition, ‘stabilised’ tip/stalk cell patterns show sensitivity to the formation of new cell-cell junctions during fusion: we predict cell fates can reverse. The fusing tip cells become inhibited and neighbouring stalk cells flip fate, recursively providing new tip cells. Junction size emerges as a key factor in establishing a stable tip/stalk pattern. Cell-cell junctions elongate as tip cells migrate, which is shown to provide positive feedback to lateral inhibition, causing it to be more susceptible to pathological oscillations. Importantly, down-regulation of the migratory pathway alone is shown to be sufficient to rescue the sprouting system from oscillation and restore stability. Thus we suggest the use of migration inhibitors as therapeutic agents for vascular normalisation in cancer