Abstract T5: Molecular Mechanisms Involved In The Vascular Protective Effects Of Mas1 And Et
            B
            R Interaction

We demonstrated that Mas1 and ET B R physically interact in endothelial cells inducing Ang-(1-7) vascular protection. Using high throughput screening of >20,000 druggable compounds, we identified a number of molecules that enhance Mas1:ET B R interactions. Of these, 2 potently enhanced interaction between the receptors. These enhancers (Enh), termed Enh3 and Enh4 were used to assess Mas1:ET B R interaction and cellular functional responses in vascular smooth muscle cells (VSMCs) from normotensive WKY and hypertensive SHRSP rats. Cells were exposed to Enh 3 and Enh4 (10 -5 M) for short (5,15 and 30min) and long timepoints (5hours). Expression of signaling molecules was assessed by immunoblotting and Ca 2+ influx was evaluated using fluorescence microscopy. In WKY VSMCs, Enh 3 short term stimulation reduced basal ERK1/2 phosphorylation (26.8±5.9% vs veh, p<0.01), an effect absent in SHRSP VSMCs, while Enh 4 had no effect. Short term exposure to Enh 4, but not Enh3, reduced basal MLC20 phosphorylation (54.9±7.5% vs veh, p<0.001) in WKY but not in SHRSP VSMCs. In SHRSP VSMCs, Enh 3, but not Enh4, reduced basal AKT phosphorylation (63.5±8.9% vs veh, p<0.001). Long term stimulation with Enh 3 reduced expression of AKT (38.0±2.0% vs veh, p<0.001), PCNA (60.0±7.0% vs veh, p<0.001), and VCAM-1 (35.0±8.0% vs veh, p<0.001) in WKY VSMCs. Similarly, AKT (35.0±12.0% vs veh, p<0.05) expression was reduced by Enh 3, with no effect on other markers in SHRSP VSMCs. Enh 4 long-term stimulation reduced AKT expression (30.0±10.0% vs veh, p<0.05) in WKY VSMCs, without effect on SHRSP VSMCs. ET-1 induced Ca 2+ influx in WKY and SHRSP VSMCs was unaffected by Enh3 and Enh4. In conclusion, enhancing Mas1:ET B R interaction attenuates mitogenic and pro-inflammatory signaling pathways in WKY and SHRSP VSMCs. Enhancing interaction between these receptors does not increase Ca 2+ signaling, important in VSMC contraction. Our data suggest that Enh3 and Enh4 may have VSMC protective effects and that they do not amplify injurious signaling induced by ET-1/ETBR. These findings identify a potential new strategy in vasoprotection.

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Short-term exposure and long-term consequences of neonatal exposure to Δ9-tetrahydrocannabinol (THC) and ibuprofen in mice

Behavioural Brain Research ◽

10.1016/j.bbr.2016.04.001 ◽

2016 ◽

Vol 307 ◽

pp. 137-144 ◽

Cited By ~ 18

Author(s):

Gaëtan Philippot ◽

Fred Nyberg ◽

Torsten Gordh ◽

Anders Fredriksson ◽

Henrik Viberg

Keyword(s):

Neonatal Exposure ◽

Short Term ◽

Short Term Exposure ◽

Long Term Consequences

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Spatio-temporal associations of air pollutant concentrations, GP respiratory consultations and respiratory inhaler prescriptions: a 5-year study of primary care in the borough of Lambeth, South London

Environmental Health ◽

10.1186/s12940-021-00730-1 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Mark Ashworth ◽

◽

Antonis Analitis ◽

David Whitney ◽

Evangelia Samoli ◽

...

Keyword(s):

Primary Care ◽

Negative Binomial ◽

Hospital Admissions ◽

Air Pollutant ◽

Respiratory Morbidity ◽

Short Term ◽

Short Term Exposure ◽

Short And Long Term ◽

Spatio Temporal

Abstract Background Although the associations of outdoor air pollution exposure with mortality and hospital admissions are well established, few previous studies have reported on primary care clinical and prescribing data. We assessed the associations of short and long-term pollutant exposures with General Practitioner respiratory consultations and inhaler prescriptions. Methods Daily primary care data, for 2009–2013, were obtained from Lambeth DataNet (LDN), an anonymised dataset containing coded data from all patients (1.2 million) registered at general practices in Lambeth, an inner-city south London borough. Counts of respiratory consultations and inhaler prescriptions by day and Lower Super Output Area (LSOA) of residence were constructed. We developed models for predicting daily PM2.5, PM10, NO2 and O3 per LSOA. We used spatio-temporal mixed effects zero inflated negative binomial models to investigate the simultaneous short- and long-term effects of exposure to pollutants on the number of events. Results The mean concentrations of NO2, PM10, PM2.5 and O3 over the study period were 50.7, 21.2, 15.6, and 49.9 μg/m3 respectively, with all pollutants except NO2 having much larger temporal rather than spatial variability. Following short-term exposure increases to PM10, NO2 and PM2.5 the number of consultations and inhaler prescriptions were found to increase, especially for PM10 exposure in children which was associated with increases in daily respiratory consultations of 3.4% and inhaler prescriptions of 0.8%, per PM10 interquartile range (IQR) increase. Associations further increased after adjustment for weekly average exposures, rising to 6.1 and 1.2%, respectively, for weekly average PM10 exposure. In contrast, a short-term increase in O3 exposure was associated with decreased number of respiratory consultations. No association was found between long-term exposures to PM10, PM2.5 and NO2 and number of respiratory consultations. Long-term exposure to NO2 was associated with an increase (8%) in preventer inhaler prescriptions only. Conclusions We found increases in the daily number of GP respiratory consultations and inhaler prescriptions following short-term increases in exposure to NO2, PM10 and PM2.5. These associations are more pronounced in children and persist for at least a week. The association with long term exposure to NO2 and preventer inhaler prescriptions indicates likely increased chronic respiratory morbidity.

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Effects of Long-Term Triclosan Exposure on Microbiota in Zebrafish

Frontiers in Microbiology ◽

10.3389/fmicb.2021.604313 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ning Tang ◽

Pianpian Fan ◽

Xiaogang Yu ◽

Rui Ma ◽

Yexuan Tao ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Early Adulthood ◽

Rrna Gene ◽

Adult Zebrafish ◽

Short Term ◽

Microbial Composition ◽

Short Term Exposure ◽

Embryonic Life ◽

A Minor

Background: Triclosan (TCS) is a widely used antibacterial agent in personal care products and is ubiquitous in the environment. We aimed to examine whether TCS exposure affects microbiota in the gastrointestinal tract of zebrafish.Methods: After exposure to TCS 0 (Dimethyl Sulphoxide, DMSO control), 0.03, 0.3, 3, 30, 100, and 300ng/ml, respectively, from day 0 to 120days post fertilization (dpf), or for 7days in adult 4-month zebrafish, the long- and short-term impact of TCS exposure on the microbiome in the gastrointestinal tract was evaluated by analyzing 16S rRNA gene V3-V4 region sequencing.Results: The top two most dominant microbiota phyla were Proteobacteria and Fusobacteria phylum in all zebrafish groups. In TCS exposure 0–120 dpf, compared with DMSO control, the mean number of microbial operational taxonomic units (OTUs) was 54.46 lower (p<0.0001), Chao indice 41.40 lower (p=0.0004), and Ace indice 34.10 lower (p=0.0044) in TCS 300ng/ml group, but no change was observed in most of the other TCS concentrations. PCoA diagram showed that the microbial community in the long-term TCS 300ng/ml exposure group clustered differently from those in the DMSO control and other TCS exposure groups. A shorter body length of the zebrafish was observed in the long-term TCS exposure at 0.03, 100, and 300ng/ml. For 7-day short-term exposure in adult zebrafish, no difference was observed in alpha or beta diversity of microbiota nor the relative abundance of Proteobacteria or Fusobacteria phylum among DMSO control and any TCS levels, but a minor difference in microbial composition was observed for TCS exposure.Conclusions: Long-term exposure to high TCS concentration in a window from early embryonic life to early adulthood may reduce diversity and alter the composition of microbiota in the gastrointestinal tract. The effect of short-term TCS exposure was not observed on the diversity of microbiota but there was a minor change of microbial composition in adult zebrafish with TCS exposure.

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Short-term exposure to air pollution (PM2.5) induces hypothalamic inflammation, and long-term leads to leptin resistance and obesity via Tlr4/Ikbke in mice

Scientific Reports ◽

10.1038/s41598-020-67040-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Clara Machado Campolim ◽

Lais Weissmann ◽

Clílton Kraüss de Oliveira Ferreira ◽

Olivia Pizetta Zordão ◽

Ana Paula Segantine Dornellas ◽

...

Keyword(s):

Air Pollution ◽

Leptin Resistance ◽

Short Term ◽

Short Term Exposure ◽

Hypothalamic Inflammation

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Intestinal Explant Cultures from Gilthead Seabream (Sparus aurata, L.) Allowed the Determination of Mucosal Sensitivity to Bacterial Pathogens and the Impact of a Plant Protein Diet

International Journal of Molecular Sciences ◽

10.3390/ijms21207584 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7584

Author(s):

David Sánchez Peñaranda ◽

Christine Bäuerl ◽

Ana Tomás-Vidal ◽

Miguel Jover-Cerdá ◽

Guillem Estruch ◽

...

Keyword(s):

Immune Response ◽

Phase Ii ◽

Plant Protein ◽

Gilthead Seabream ◽

Growth Stages ◽

Short Term ◽

Short Term Exposure ◽

Cox 2 ◽

The Impact

The interaction between diet and intestinal health has been widely discussed, although in vivo approaches have reported limitations. The intestine explant culture system developed provides an advantage since it reduces the number of experimental fish and increases the time of incubation compared to similar methods, becoming a valuable tool in the study of the interactions between pathogenic bacteria, rearing conditions, or dietary components and fish gut immune response. The objective of this study was to determine the influence of the total substitution of fish meal by plants on the immune intestinal status of seabream using an ex vivo bacterial challenge. For this aim, two growth stages of fish were assayed (12 g): phase I (90 days), up to 68 g, and phase II (305 days), up to 250 g. Additionally, in phase II, the effects of long term and short term exposure (15 days) to a plant protein (PP) diet were determined. PP diet altered the mucosal immune homeostasis, the younger fish being more sensitive, and the intestine from fish fed short-term plant diets showed a higher immune response than with long-term feeding. Vibrio alginolyticus (V. alginolyticus) triggered the highest immune and inflammatory response, while COX-2 expression was significantly induced by Photobacterium damselae subsp. Piscicida (P. damselae subsp. Piscicida), showing a positive high correlation between the pro-inflammatory genes encoding interleukin 1β (IL1-β), interleukin 6 (IL-6) and cyclooxygenase 2(COX-2).

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Short-term exposure of Chinook salmon (Oncoryhnchus tshawytscha) to o,p-DDE or DMSO during early life-history stages causes long-term humoral immunosuppression.

Environmental Health Perspectives ◽

10.1289/ehp.6171 ◽

2003 ◽

Vol 111 (13) ◽

pp. 1601-1607 ◽

Cited By ~ 41

Author(s):

Ruth H Milston ◽

Martin S Fitzpatrick ◽

Anthony T Vella ◽

Shaun Clements ◽

Deke Gundersen ◽

...

Keyword(s):

Life History ◽

Chinook Salmon ◽

Early Life ◽

Early Life History ◽

Short Term ◽

Life History Stages ◽

Short Term Exposure

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Molecular Mechanisms of Oxytocin Signaling at the Synaptic Connection

Neural Plasticity ◽

10.1155/2018/4864107 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Jan Bakos ◽

Annamaria Srancikova ◽

Tomas Havranek ◽

Zuzana Bacova

Keyword(s):

Neurodevelopmental Disorders ◽

Molecular Mechanisms ◽

Neuronal Excitability ◽

Molecular Level ◽

Short Term ◽

Oxytocin Receptors ◽

Potential Therapeutic Intervention ◽

Early Alteration

Aberrant regulation of oxytocin signaling is associated with the etiology of neurodevelopmental disorders. Synaptic dysfunctions in neurodevelopmental disorders are becoming increasingly known, and their pathogenic mechanisms could be a target of potential therapeutic intervention. Therefore, it is important to pay attention to the role of oxytocin and its receptor in synapse structure, function, and neuron connectivity. An early alteration in oxytocin signaling may disturb neuronal maturation and may have short-term and long-term pathological consequences. At the molecular level, neurodevelopmental disorders include alterations in cytoskeletal rearrangement and neuritogenesis resulting in a diversity of synaptopathies. The presence of oxytocin receptors in the presynaptic and postsynaptic membranes and the direct effects of oxytocin on neuronal excitability by regulating the activity of ion channels in the cell membrane implicate that alterations in oxytocin signaling could be involved in synaptopathies. The ability of oxytocin to modulate neurogenesis, synaptic plasticity, and certain parameters of cytoskeletal arrangement is discussed in the present review.

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Contrasting seed germination responses to red and far-red light in Leptospermum scoparium and Melicytus ramiflorus

Functional Plant Biology ◽

10.1071/pp00024 ◽

2000 ◽

Vol 27 (11) ◽

pp. 1069

Author(s):

Helen Herron ◽

John Clemens ◽

Dennis H. Greer

Keyword(s):

Seed Germination ◽

Red Light ◽

Green Light ◽

Photon Flux ◽

Short Term ◽

Short Term Exposure ◽

Subsequent Exposure ◽

R:Fr Ratio ◽

Leptospermum Scoparium

Effects of red light (R) and far-red light (FR), and selected photon flux densities (PFD) of photosynthetically active radiation (PAR) on seed germination in the photoblastic, primary colonising species Leptospermum scoparium J. R. et G. Forst. and the late secondary successional Melicytus ramiflorus J. R. et G. Forst. were studied. A continuous R dose response curve forL. scoparium germination was developed, unifying data from experiments using long-term exposure to PAR with those following short-term exposure to R. The threshold R dose needed to effect germination was ~0.1 mmol m –2 , and the response was saturated at 1000 mmol m –2 . Stimulation of germination by R was reversed by a subsequent exposure to FR. These features are consistent with a low-fluence response mediated by phytochrome B. FR reversal of germination was achieved at a dose two orders of magnitude lower than that of R required to induce initial germination. However, when both R and FR were provided simultaneously, the FR dose needed to even partially inhibit germination (34% compared to > 95% in controls) was two orders of magnitude higher than the R dose (R:FR ratio = 0.007). Germination in L. scoparium was also stimulated in up to 12% of seed upon diurnal exposure to FR, or by green light (~2 mol m –2 ), indicating a very-low-fluence response mediated by phytochrome A also operating in this species. In contrast, seed germination in M. ramiflorus was relatively unresponsive to R, and secondary dormancy was induced by high PFD (515 mol m –2 s –1 ).

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Long-term regulation of hexose uptake by isoproterenol in cultured 3T3 adipocytes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1985.248.6.e706 ◽

1985 ◽

Vol 248 (6) ◽

pp. E706-E711 ◽

Cited By ~ 2

Author(s):

J. P. van Putten ◽

H. M. Krans

Keyword(s):

Protein Synthesis ◽

Prolonged Exposure ◽

Term Effect ◽

Long Term Effects ◽

Fat Cell ◽

Short Term ◽

Long Term Effect ◽

Short Term Exposure ◽

Hexose Uptake

Catecholamines are known to have short-term regulatory effects on fat cell hexose uptake. We examined the long-term effects of catecholamines on the insulin-sensitive 2-deoxyglucose (dGlc) uptake in cultured 3T3-L1 adipocytes. Prolonged exposure (48 h) to isoproterenol (beta-adrenergic agonist) stimulated the basal dGlc uptake up to 90%. The effect was specific, time, concentration, and protein synthesis dependent and reversible. The effect of insulin was unaltered and superimposed on the increase in basal dGlc uptake. The long-term effect of isoproterenol was mimicked by epinephrine, dibutyryl cAMP (DBcAMP), and 1-methyl-3-isobutylxanthine (IBMX). By contrast, short-term exposure to isoproterenol (and epinephrine) induced a protein synthesis-independent increase in basal dGlc uptake (30%) not accompanied by an increase in insulin responsiveness. Moreover, on short-term basis, DBcAMP and IBMX suppressed both the basal and insulin-stimulated uptake up to 50%. Determination of the intracellular nonphosphorylated dGlc during the uptake and of the hexokinase activity revealed that the long-term effect of isoproterenol was most likely due to alterations low in dGlc transport. In conclusion, long-term regulators of hexose uptake are in cultured 3T3-L1 adipocytes, isoproterenol, and other cAMP stimulators. The long-term effect is independent from the short-term regulatory effect of the agents and from the effect of insulin.

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Transcriptional Responses of Escherichia coli K-12 and O157:H7 Associated with Lettuce Leaves

Applied and Environmental Microbiology ◽

10.1128/aem.07454-11 ◽

2012 ◽

Vol 78 (6) ◽

pp. 1752-1764 ◽

Cited By ~ 64

Author(s):

Ryan C. Fink ◽

Elaine P. Black ◽

Zhe Hou ◽

Masayuki Sugawara ◽

Michael J. Sadowsky ◽

...

Keyword(s):

Escherichia Coli ◽

Molecular Mechanisms ◽

Leaf Surface ◽

Short Term ◽

Transcriptional Responses ◽

Content Type ◽

E Coli ◽

Leaf Surfaces ◽

K 12

ABSTRACTAn increasing number of outbreaks of gastroenteritis recently caused byEscherichia coliO157:H7 have been linked to the consumption of leafy green vegetables. Although it is known thatE. colisurvives and grows in the phyllosphere of lettuce plants, the molecular mechanisms by which this bacterium associates with plants are largely unknown. The goal of this study was to identifyE. coligenes relevant to its interaction, survival, or attachment to lettuce leaf surfaces, comparingE. coliK-12, a model system, andE. coliO157:H7, a pathogen associated with a large number of outbreaks. Using microarrays, we found that upon interaction with intact leaves, 10.1% and 8.7% of the 3,798 shared genes were differentially expressed in K-12 and O157:H7, respectively, whereas 3.1% changed transcript levels in both. The largest group of genes downregulated consisted of those involved in energy metabolism, includingtnaA(33-fold change), encoding a tryptophanase that converts tryptophan into indole. Genes involved in biofilm modulation (bhsAandybiM) and curli production (csgAandcsgB) were significantly upregulated inE. coliK-12 and O157:H7. BothcsgAandbhsA(ycfR) mutants were impaired in the long-term colonization of the leaf surface, but onlycsgAmutants had diminished ability in short-term attachment experiments. Our data suggested that the interaction ofE. coliK-12 and O157:H7 with undamaged lettuce leaves likely is initiated via attachment to the leaf surface using curli fibers, a downward shift in their metabolism, and the suppression of biofilm formation.

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