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•Demethylation and ring-A opening of triterpenoids occur prior to mangrove leaf abscission.•Up to 31 aliphatic and aromatic des-A-triterpenes were detected in mangrove stand ...soils.•Early diagenetic degradation scheme for mangrove derived taraxerol is proposed.
Leaves from three mangrove species, and surface and deeper soils along salinity gradients in the Shark River estuary, USA, were analyzed to determine numerous diagenetic degradation products and pathways for mangrove derived triterpenoids. The dehydration of pentacyclic triterpenols was observed in mangrove leaves, leading to pentacyclic triterpadienes with Δ2,12 and Δ2,14 unsaturations. Surprisingly, various mono-unsaturated triterpenes (with Δ12 and Δ14), nor-, bisnor- (24,25-bisnortaraxer-14-ene), trisnor-triterpenes (1,2,3-trisnortaraxera-5(10),14-diene and 1,2,3-trisnortaraxer-14-ene) and tetrakisnor- and pentakisnor-triterpenes were detected in Rhizophora mangle leaves, suggesting that reduction and later demethylation of triterpadienes can occur prior to mangrove leaf abscission or senescence/death. Most of the unsaturated and nortriterpenes were also found in mangrove stand soils (>100 years old), suggesting their relative stability. In addition, a high diversity of aliphatic and aromatic des-A-triterpenes from the taraxerane, oleanane, ursane, and lupane precursors were present in the surface and deeper soils of mangrove stands, suggesting that isomerization, rapid diagenetic loss of ring-A and further aromatization of triterpenoids occurred early during litter decay. The overall diagenetic transformations could be caused by a combination of photodegradation, microbial alteration (bacteria/fungi), anaerobic alteration (reduction), oxidation and secondary processes. Possible mechanisms of the early diagenesis of triterpenoids were proposed using taraxerol, a triterpenol, highly enriched in R. mangle, as an example. These results, coupled with the detection of various intermediate compounds, provide a better understanding of the diagenetic fate of mangrove derived triterpenoids.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
OBJECTIVE:The lymphatic system is a circulatory system that unidirectionally drains the interstitial tissue fluid back to blood circulation. Although lymph is utilized by leukocytes for immune ...surveillance, it remains inaccessible to platelets and erythrocytes. Activated cells release submicron extracellular vesicles (EV) that transport molecules from the donor cell. In rheumatoid arthritis, EV accumulate in the joint where they can interact with numerous cellular lineages. However, whether EV can exit the inflamed tissue to recirculate is unknown. Here, we investigated whether vascular leakage that occurs during inflammation could favor EV access to the lymphatic system.
APPROACH AND RESULTS:Using an in vivo model of autoimmune inflammatory arthritis, we show that there is an influx of platelet EV, but not EV from erythrocytes or leukocytes, in joint-draining lymph. In contrast to blood platelet EV, lymph platelet EV lacked mitochondrial organelles and failed to promote coagulation. Platelet EV influx in lymph was consistent with joint vascular leakage and implicated the fibrinogen receptor α2bβ3 and platelet-derived serotonin.
CONCLUSIONS:These findings show that platelets can disseminate their EV in fluid that is inaccessible to platelets and beyond the joint in this disease.
The objectives were to compare the performance of a segmentation algorithm, based on the minimization of an uncertainty function, to delineate contours of external elastic membrane and lumen of human ...coronary arteries imaged with 40 and 60 MHz IVUS, and to use values of this function to delineate portions of contours with highest uncertainty. For 8 patients, 40 and 60 MHz IVUS coronary data acquired pre- and post-interventions were used, for a total of 68,516 images. Manual segmentations of contours (on 2312 images) performed by experts at three core laboratories were the gold-standards. Inter-expert variability was highest on contour points with largest values of the uncertainty function (p < 0.001). Inter-expert variability was lower at 60 than 40 MHz for external elastic membrane (p = 0.013) and lumen (p = 0.024). Average differences in plaque (and atheroma) burden between algorithmic contours and experts' contours were within inter-expert variability (p < 0.001).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Navigating risk of predation is a major driver of behavioral decision-making in small fishes. Fish use personal information from olfactory and visual indicators of risk, and also rely upon social ...cues to inform behavioral trade-offs between risk avoidance and fitness-positive activities such as foraging. Here, fathead minnows (
Pimephales promelas
), were captured, clipped and released at 48 field sites chemically labeled with either fathead minnow alarm cue (high risk) or water (low risk). We removed the chemical label after 2 h, then monitored area use by clipped and non-clipped fish. In addition, a shoal was placed in traps in half of the risky and half of the safe locations as a visual social cue of safety. We caught 2919 fish in the first sample, of which 594 were fathead minnows. These were clipped and released. The second sample caught 1500 fish, of which 164 were fathead minnows including 11 bearing marks from the first sample. Non-clipped fathead minnows and northern redbelly dace in the general community, which lacked personal information about risk status associated with trap sites, avoided areas previously labeled with alarm cues for at least 2 h after the source of alarm cue was removed, unless an experimental shoal was present at the risky site, in which case they joined the shoal in the trap. Clipped fathead minnows with direct personal knowledge of risk showed a significant shift away from areas labeled with conspecific alarm cue and a significant attraction toward sites seeded with a shoal. Moreover, unlike non-clipped fish in the general community, clipped fathead minnows were not influenced by experimental shoals at sites previously labeled as risky. These data indicate that the influence of social cues of safety depend on whether individual minnows have access to recent personal information about risk.
Significance statement
Animals use information for making decisions about when and where it is safe. Information comes from direct personal experience and/or from observing the behavior of others (social cues). In this study minnows with different levels of personal knowledge about risk responded differently to social cues about safety. Naïve minnows relied on social cues while minnows with personal knowledge of risk associated with an area ignored social cues. This study, conducted on free-living fish in a natural population, show how fish use information about risk and safety when the risk of predation is highly variable in space and time.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Mars Global Surveyor spacecraft, in a highly elliptical polar orbit, obtained vector magnetic field measurements above the surface of Mars (altitudes >100 kilometers). Crustal magnetization, ...mainly confined to the most ancient, heavily cratered martian highlands, is frequently organized in east-west-trending linear features, the longest extending over 2000 kilometers. Crustal remanent magnetization exceeds that of terrestrial crust by more than an order of magnitude. Groups of quasi-parallel linear features of alternating magnetic polarity were found. They are reminiscent of similar magnetic features associated with sea floor spreading and crustal genesis on Earth but with a much larger spatial scale. They may be a relic of an era of plate tectonics on Mars.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
To evaluate whether school nurses can assist pediatricians in providing asthma care and reduce school absenteeism through a program called Easy Breathing for Schools (EzBfS), a 5-element school ...nurse-led asthma management program and the effectiveness in reducing school absenteeism.
Fifteen public school nurses in an urban community implemented EzBfS during the 2015–16 and 2016–17 school years. Program elements included assessment of asthma risk and asthma control, asthma education, medication review, and a pediatrician communication tool. School absence for any reason was the primary outcome; absentee rates for students with asthma enrolled in the program were compared to students with asthma in the entire school population using negative binomial regression.
School nurses enrolled 251/2,126 students with physician-confirmed asthma (2015–16: n = 114 and 2016–17: n = 137). Sixty eight percent of participants were Latino and 25% were Black with a mean age of 8.7 ± 2.2 years. Absentee rates were higher in children with asthma compared to children without asthma (8.3% vs 7.0% absent, respectively P < .001). Students enrolled in the program experienced a 25% decrease in absentee rate after adjusting for age, sex, race/ethnicity, and school year (rate ratio = 0.75, 95% confidence interval, 0.67, 0.85) as compared to students with asthma not enrolled in the program. Participants also demonstrated improvement in inhaler technique score (P < .001). Ninety two percent of the nurses were satisfied with the program.
EzBfS, a pragmatic, nurse-led asthma management program, was successfully implemented by school nurses and significantly decreased school absences among a sample of students with asthma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, VSZLJ, ZAGLJ, ZRSKP
Variability in response to short-acting β
-agonists (e.g., albuterol) among patients with asthma from diverse racial/ethnic groups may contribute to asthma disparities. We sought to identify genetic ...variants associated with bronchodilator response (BDR) to identify potential mechanisms of drug response and risk factors for worse asthma outcomes. Genome-wide association studies of bronchodilator response (BDR) were performed using TOPMed Whole Genome Sequencing data of the Asthma Translational Genomic Collaboration (ATGC), which corresponded to 1136 Puerto Rican, 656 Mexican and 4337 African American patients with asthma. With the population-specific GWAS results, a trans-ethnic meta-analysis was performed to identify BDR-associated variants shared across the three populations. Replication analysis was carried out in three pediatric asthma cohorts, including CAMP (Childhood Asthma Management Program; n = 560), GACRS (Genetics of Asthma in Costa Rica Study; n = 967) and HPR (Hartford-Puerto Rico; n = 417). A genome-wide significant locus (rs35661809; P = 3.61 × 10
) in LINC02220, a non-coding RNA gene, was identified in Puerto Ricans. While this region was devoid of protein-coding genes, capture Hi-C data showed a distal interaction with the promoter of the DNAH5 gene in lung tissue. In replication analysis, the GACRS cohort yielded a nominal association (1-tailed P < 0.05). No genetic variant was associated with BDR at the genome-wide significant threshold in Mexicans and African Americans. Our findings help inform genetic underpinnings of BDR for understudied minority patients with asthma, but the limited availability of genetic data for racial/ethnic minority children with asthma remains a paramount challenge.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
499.
Pompe disease gene therapy BYRNE, Barry J; FALK, Darin J; CLOUTIER, Denise A ...
Human molecular genetics,
04/2011, Volume:
20, Issue:
1
Journal Article
Peer reviewed
Open access
Pompe disease is an autosomal recessive metabolic myopathy caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase and results in cellular lysosomal and cytoplasmic glycogen ...accumulation. A wide spectrum of disease exists from hypotonia and severe cardiac hypertrophy in the first few months of life due to severe mutations to a milder form with the onset of symptoms in adulthood. In either condition, the involvement of several systems leads to progressive weakness and disability. In early-onset severe cases, the natural history is characteristically cardiorespiratory failure and death in the first year of life. Since the advent of enzyme replacement therapy (ERT), the clinical outcomes have improved. However, it has become apparent that a new natural history is being defined in which some patients have substantial improvement following ERT, while others develop chronic disability reminiscent of the late-onset disease. In order to improve on the current clinical outcomes in Pompe patients with diminished clinical response to ERT, we sought to address the cause and potential for the treatment of disease manifestations which are not amenable to ERT. In this review, we will focus on the preclinical studies that are relevant to the development of a gene therapy strategy for Pompe disease, and have led to the first clinical trial of recombinant adeno-associated virus-mediated gene-based therapy for Pompe disease. We will cover the preliminary laboratory studies and rationale for a clinical trial, which is based on the treatment of the high rate of respiratory failure in the early-onset patients receiving ERT.
Hydrothermal magnetite from the Starra iron oxide‑copper gold (IOCG) deposit in northwest Queensland, Australia, records a gradual decrease in V, Ni, Cr, and Mn that correlates with the transition ...from early, amphibole-biotite-magnetite dominant alteration to late, chlorite-quartz-hematite-dominated alteration assemblages. The observed systematic change in multivariate elements in magnetite is interpreted to indicate an increase in fO2 during the main Cu(Au) mineralization. We suggest that variations in the V, Ni, and Cr contents of magnetite at Starra indicate either a primary magmatic fluid source or the leaching of mafic rocks by fluids during early albitization. Late silician magnetite contained in ankerite veins that crosscut the preexisting alteration assemblages in the hanging wall to the Starra 222 ore body is likely the result of a second mineralization phase, which contributed additional metals to the Starra ore bodies.
Existing data on magnetite chemistry from several IOA, IOCG, Fe, and FeW skarn deposits show that the ratio of V to Ga discriminates the various ore types effectively. Skarn deposits are separated from IOA and IOCG by lower concentrations of V, Ni, and Cr, suggesting a more primitive fluid source or the precipitation of magnetite at distinct physicochemical conditions than IOA and IOCG deposits. Magnetite from IOA deposits exhibits a consistently elevated V concentration whereas magnetite from Fe(W) skarn records an increase in V concentration with the evolution of the system. A pronounced decrease in the V contents of magnetite associated with CuAu mineralization at Starra is interpreted as a change in redox conditions from reduced to oxidized at the time of mineralization. Such variations are also observed in other IOCG deposits. We propose that systematic decreases in V concentration in magnetite during the paragenetic evolution of the host mineral system is a diagnostic indicator for Cu(Au) mineralization in IOCG deposits, and as such, it may be used as a proxy for CuAu exploration, if the paragenetic context of magnetite is well constrained.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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