169 research outputs found

    Distribution of hydrogen peroxide and methylhydroperoxide over the Pacific and South Atlantic Oceans

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    The gas phase hydrogen peroxide and methylhydroperoxide concentrations were measured in the troposphere over the tropical Pacific Ocean as a component of NASA's Global Tropospheric Experiment/Pacific Exploratory Mission-Tropics A field campaign. Flights on two aircraft covered the Pacific from 70°S to 60°N and 110°E to 80°W and South Atlantic from 40°S to 15°N and 45°W to 70°E, and extending from 76 to 13,000 m altitude. H2O2 and CH3OOH have the highest concentrations at a given altitude at the equator and decrease with increasing latitude in both the northern and southern hemispheres. Above 4 km the gradient is substantially reduced for both H2O2 and CH3OOH with latitude, and at altitudes in excess of 8 km there is no latitudinal dependence. H2O2 and CH3OOH exhibit maximum mixing ratios between 1 and 2 km at all latitudes. The mean mixing ratio of H2O2 at the equator was 1600 ± 600 parts per trillion by volume (pptv) decreasing to 500 ± 250 pptv at latitudes greater than 55° north and south between 1 and 2 km altitude. CH3OOH at the equator was 1400 ± 250 pptv, decreasing to 330 ± 200 pptv at high latitudes at altitudes between 1 and 2 km. The concentration of peroxides at high latitudes in the northern hemisphere was generally a factor of 2 higher than at corresponding latitudes in the southern hemisphere. The ratio of H2O2 to CH3OOH was between 1 and 2 from 45°S to 35°N at altitudes below 4 km. Between 5° to 15°N the ratio is less than 1, due to preferential removal of H2O2 in the Intertropical Convergence Zone. Copyright 1999 by the American Geophysical Union

    Circles in the sea: annual courtship “torus” behaviour of basking sharks Cetorhinus maximus identified in the eastern North Atlantic Ocean

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    Groups of basking sharks engaged in circling behaviour are rarely observed, and their function remains enigmatic in the absence of detailed observations. Here, underwater and aerial video recordings of multiple circling groups of basking sharks during late summer (August and September 2016–2021) in the eastern North Atlantic Ocean showed groups numbering between 6 and 23 non-feeding individuals of both sexes. Sharks swam slowly in a rotating “torus” (diameter range: 17–39 m), with individuals layered vertically from the surface to a maximum depth of 16 m. Within a torus, sharks engaged in close-following, echelon, close-flank approach or parallel-swimming behaviours. Measured shark total body lengths were 5.4–9.5 m (mean LT: 7.3 m ± 0.9 s.d.; median: 7.2 m, n = 27), overlapping known lengths of sexually mature males and females. Males possessed large claspers with abrasions that were also observed on female pectoral fins. Female body colouration was paler than that of males, similar to colour changes observed during courtship and mating in other shark species. Individuals associated with most other members rapidly (within minutes), indicating toroidal behaviours facilitate multiple interactions. Sharks interacted through fin–fin and fin–body contacts, rolling to expose the ventral surfaces to following sharks, and breaching behaviour. Toruses formed in late summer when feeding aggregations in zooplankton-rich thermal fronts switched to non-feeding following and circling behaviours. Collectively, the observations explain a courtship function for toruses. This study highlights northeast Atlantic coastal waters as a critical habitat supporting courtship reproductive behaviour of endangered basking sharks, the first such habitat identified for this species globally

    Glycogen Synthase Kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells

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    Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by facilitating PCAF-mediated H3K9 acetylation, but the molecular mechanism by which NM1 is regulated remains unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK) 3β phosphorylates and stabilizes NM1, allowing for NM1 association with the chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the rDNA as active GSK3β selectively occupies the gene. ChIP assays and transmission electron microscopy in GSK3β-/- mouse embryonic fibroblasts indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9 acetylation leading to a chromatin state incompatible with transcription. We found that GSK3β directly phosphorylates the endogenous NM1 on a single serine residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β-mediated phosphorylation of NM1 is required for pol I transcription activation

    Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma

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    <p>Abstract</p> <p>Background</p> <p>Asthma can be difficult to diagnose, but bronchial provocation with methacholine, exercise or mannitol is helpful when used to identify bronchial hyperresponsiveness (BHR), a key feature of the disease. The utility of these tests in subjects with signs and symptoms of asthma but without a clear diagnosis has not been investigated. We investigated the sensitivity and specificity of mannitol to identify exercise-induced bronchoconstriction (EIB) as a manifestation of BHR; compared this with methacholine; and compared the sensitivity and specificity of mannitol and methacholine for a clinician diagnosis of asthma.</p> <p>Methods</p> <p>509 people (6–50 yr) were enrolled, 78% were atopic, median FEV<sub>1 </sub>92.5% predicted, and a low NAEPPII asthma score of 1.2. Subjects with symptoms of seasonal allergy were excluded. BHR to exercise was defined as a ≥ 10% fall in FEV<sub>1 </sub>on at least one of two tests, to methacholine a PC<sub>20 </sub>≤ 16 mg/ml and to mannitol a 15% fall in FEV<sub>1 </sub>at ≤ 635 mg or a 10% fall between doses. The clinician diagnosis of asthma was made on examination, history, skin tests, questionnaire and response to exercise but they were blind to the mannitol and methacholine results.</p> <p>Results</p> <p>Mannitol and methacholine were therapeutically equivalent to identify EIB, a clinician diagnosis of asthma, and prevalence of BHR. The sensitivity/specificity of mannitol to identify EIB was 59%/65% and for methacholine it was 56%/69%. The BHR was mild. Mean EIB % fall in FEV<sub>1 </sub>in subjects positive to exercise was 19%, (SD 9.2), mannitol PD<sub>15 </sub>158 (CI:129,193) mg, and methacholine PC<sub>20 </sub>2.1(CI:1.7, 2.6)mg/ml. The prevalence of BHR was the same: for exercise (43.5%), mannitol (44.8%), and methacholine (41.6%) with a test agreement between 62 & 69%. The sensitivity and specificity for a clinician diagnosis of asthma was 56%/73% for mannitol and 51%/75% for methacholine. The sensitivity increased to 73% and 72% for mannitol and methacholine when two exercise tests were positive.</p> <p>Conclusion</p> <p>In this group with normal FEV<sub>1</sub>, mild symptoms, and mild BHR, the sensitivity and specificity for both mannitol and methacholine to identify EIB and a clinician diagnosis of asthma were equivalent, but lower than previously documented in well-defined populations.</p> <p>Trial registration</p> <p>This was a multi-center trial comprising 25 sites across the United States of America. (NCT0025229).</p

    Convulsant Doses of a Dopamine D1 Receptor Agonist Result in Erk-Dependent Increases in Zif268 and Arc/Arg3.1 Expression in Mouse Dentate Gyrus

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    Activation of dopamine D1 receptors (D1Rs) has been shown to induce epileptiform activity. We studied the molecular changes occurring in the hippocampus in response to the administration of the D1-type receptor agonist, SKF 81297. SKF 81297 at 2.5 and 5.0 mg/kg induced behavioural seizures. Electrophysiological recordings in the dentate gyrus revealed the presence of epileptiform discharges peaking at 30–45 min post-injection and declining by 60 min. Seizures were prevented by the D1-type receptor antagonist, SCH 23390, or the cannabinoid CB1 receptor agonist, CP 55,940. The effect of SKF 81297 was accompanied by increased phosphorylation of the extracellular signal-regulated protein kinases 1 and 2 (ERK), in the granule cells of the dentate gyrus. This effect was also observed in response to administration of other D1-type receptor agonists, such as SKF83822 and SKF83959. In addition, SKF 81297 increased the phosphorylation of the ribosomal protein S6 and histone H3, two downstream targets of ERK. These effects were prevented by genetic inactivation of D1Rs, or by pharmacological inhibition of ERK. SKF 81297 was also able to enhance the levels of Zif268 and Arc/Arg3.1, two immediate early genes involved in transcriptional regulation and synaptic plasticity. These changes may be involved in forms of activity-dependent plasticity linked to the manifestation of seizures and to the ability of dopamine to affect learning and memory

    A fatal case of recurrent amiodarone-induced thyrotoxicosis after percutaneous tracheotomy: a case report

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    <p>Abstract</p> <p>Background</p> <p>Amiodarone is a widely used antiarrythmic drug, which may produce secondary effects on the thyroid. In 14–18% of amiodarone-treated patients, there is overt thyroid dysfunction, usually in the form of amiodarone-induced thyrotoxicosis, which can be difficult to manage with standard medical treatment.</p> <p>Case presentation</p> <p>Presented is the case of a 65-year-old man, under chronic treatment of atrial fibrillation with amiodarone, who was admitted to the Intensive Care Unit with acute cardio-respiratory failure and fever. He was recently hospitalized with respiratory distress, attributed to amiodarone-induced pulmonary fibrosis. Clinical and laboratory investigation revealed thyrotoxicosis due to amiodarone treatment. He was begun on thionamide, prednisone and beta-blockers. After a short term improvement of his clinical status the patient underwent percutaneous tracheotomy due to weaning failure from mechanical ventilation, which led to the development of recurrent thyrotoxicosis, unresponsive to medical treatment. Finally, the patient developed multiple organ failure and died, seven days later.</p> <p>Conclusion</p> <p>We suggest that percutaneous tracheotomy could precipitate a thyrotoxic crisis, particularly in non-euthyroid patients suffering from concurrent severe illness and should be performed only in parallel with emergency thyroid surgery, when indicated.</p

    The CNS Stochastically Selects Motor Plan Utilizing Extrinsic and Intrinsic Representations

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    Traditionally motor studies have assumed that motor tasks are executed according to a single plan characterized by regular patterns, which corresponds to the minimum of a cost function in extrinsic or intrinsic coordinates. However, the novel via-point task examined in this paper shows distinct planning and execution stages in motion production and demonstrates that subjects randomly select from several available motor plans to perform a task. Examination of the effect of pre-training and via-point orientation on subject behavior reveals that the selection of a plan depends on previous movements and is affected by constraints both intrinsic and extrinsic of the body. These results provide new insights into the hierarchical structure of motion planning in humans, which can only be explained if the current models of motor control integrate an explicit plan selection stage

    Latent physiological factors of complex human diseases revealed by independent component analysis of clinarrays

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    <p>Abstract</p> <p>Background</p> <p>Diagnosis and treatment of patients in the clinical setting is often driven by known symptomatic factors that distinguish one particular condition from another. Treatment based on noticeable symptoms, however, is limited to the types of clinical biomarkers collected, and is prone to overlooking dysfunctions in physiological factors not easily evident to medical practitioners. We used a vector-based representation of patient clinical biomarkers, or clinarrays, to search for latent physiological factors that underlie human diseases directly from clinical laboratory data. Knowledge of these factors could be used to improve assessment of disease severity and help to refine strategies for diagnosis and monitoring disease progression.</p> <p>Results</p> <p>Applying Independent Component Analysis on clinarrays built from patient laboratory measurements revealed both known and novel concomitant physiological factors for asthma, types 1 and 2 diabetes, cystic fibrosis, and Duchenne muscular dystrophy. Serum sodium was found to be the most significant factor for both type 1 and type 2 diabetes, and was also significant in asthma. TSH3, a measure of thyroid function, and blood urea nitrogen, indicative of kidney function, were factors unique to type 1 diabetes respective to type 2 diabetes. Platelet count was significant across all the diseases analyzed.</p> <p>Conclusions</p> <p>The results demonstrate that large-scale analyses of clinical biomarkers using unsupervised methods can offer novel insights into the pathophysiological basis of human disease, and suggest novel clinical utility of established laboratory measurements.</p

    Host microenvironment in breast cancer development: Inflammatory cells, cytokines and chemokines in breast cancer progression: reciprocal tumor–microenvironment interactions

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    A comprehensive overview of breast cancer development and progression suggests that the process is influenced by intrinsic properties of the tumor cells, as well as by microenvironmental factors. Indeed, in breast carcinoma, an intensive interplay exists between the tumor cells on one hand, and inflammatory cells/cytokines/chemokines on the other. The purpose of the present review is to outline the reciprocal interactions that exist between these different elements, and to shed light on their potential involvement in breast cancer development and progression
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