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Sections of posterior intestine of the euryhaline killifish Fundulus heteroclitus adapted to sea water were stimulated by the calcium ionophore ionomycin (1 μmol l–1) in combination with agents to elevate intracellular cyclic AMP levels, 0.5 mmol l–1 dibutyryl-cyclic AMP (db-cAMP) with 0.1 mmol l–1 3-isobutyl-1-methylxanthine (IBMX). Intestinal bag preparations from recently fed animals (but not from overnight unfed animals) changed from fluid absorption (+18.9±8.30 μl cm–2 h–1 , N=8) in the untreated control period to net fluid secretion after stimulation (–7.43±1.30 μl cm–2 h–1, N=8, P<0.01; means ± s.e.m.), indicative of the capacity of teleost intestine to undergo secretion. Posterior intestinal pieces mounted in vitro in Ussing-style membrane chambers showed net Cl– uptake (+2.245±0.633 μequiv cm–2 h–1, N=7) that turned to net secretion following stimulation by ionomycin + db-cAMP + IBMX (–3.809±1.22 μequiv cm–2 h–1, N=7, P<0.01). Mucosal application of the anion channel blocker 1 mmol l–1 diphenylamine-2-carboxylate (DPC) after ionomycin + db-cAMP + IBMX treatment significantly reduced serosal-to-mucosal unidirectional Cl– flux (P<0.001), net Cl– flux (P<0.05), short-circuit current (Isc, P<0.001) and tissue conductance (Gt, P<0.001), while 0.1 mmol l–1 4,4′-diisothiocyano-2,2′-stilbene-disulphonic acid (DIDS, a blocker of anion exchange) was without effect. Stimulation by db-cAMP + IBMX (no ionomycin) significantly increased unidirectional fluxes, Isc and Gt but did not produce net Cl– secretion. Ionomycin alone produced a transient increase in Isc but had no effect on Gt and caused no significant changes in unidirectional or net Cl– fluxes. Addition of db-cAMP + IBMX after ionomycin treatment produced net secretion of Cl– and large increases in unidirectional fluxes and Gt. Cystic fibrosis transmembrane conductance regulator (CFTR) was immunocytochemically localized with a monoclonal mouse antibody to the carboxy terminus and found to be present in the cytoplasm and basolateral membranes of all enterocytes and in the brush-border membrane of some cells, whereas NKCC immunofluorescence, demonstrating the presence of the Na+/K+/2Cl– cotransporter, was present in the cytoplasm and brush-border membrane. We conclude that the teleost intestine is capable of salt and fluid secretion only if intracellular Ca2+ and cyclic AMP pathways are stimulated together and that this secretion appears to involve activation of CFTR ion channels in the apical membrane of a subpopulation of enterocytes.
Seawater teleosts drink sea water and absorb ions and fluid across the oesophagus and intestine and in this way obtain water for osmoregulation (for a review, see Loretz, 1995). In seawater teleosts, the uptake of NaCl and K+ is via a Na+/K+/2Cl– cotransporter apparently located in the apical membrane (e.g. in winter flounder Pleuronectes americanus) (O'Grady et al., 1987). Ion uptake at the apical membrane is linked to anion channels, K+ channels and Na+/K+-ATPase in the basolateral membrane of the enterocytes (Loretz, 1995). In the herbivorous marine fish Oreochromis mossambicus and in seawater-adapted rainbow trout Oncorhynchus mykiss, NaCl uptake occurs instead via parallel Na+/H+ and Cl–/HCO3– ion exchangers (Howard and Ahearn, 1988) that are also functional in acid–base balance and in rainbow trout contribute significantly to total body base excretion (Wilson et al., 1996). Recent studies suggest the co-existence of the Na+/K+/2Cl– cotransporter together with a 4,4′-diisothiocyano-2,2′-stilbene-disulphonic acid (DIDS)-sensitive anion exchange that can account for base secretion being driven by a favourable Cl– electrochemical gradient through the Cl–/HCO3– exchanger (Grosell and Jensen, 1999). Many studies showed that ion reabsorption in the intestine of the seawater-adapted teleost is accompanied by isotonic fluid reabsorption (Loretz, 1983, 1987b, 1995).
Mammalian intestine can easily be made to secrete ions and fluid by application of agents that increase cyclic AMP levels, such as cholera toxin and forskolin (Field et al., 1980). Such secretory diarrhoea is associated with common pathological conditions evoked by bacterial endotoxins. This secretion, in turn, involves activation by cyclic AMP of apically located cystic fibrosis transmembrane conductance regulator (CFTR) ion channels, thus implicating CFTR in this pathological condition (Mathews et al., 1999). Our work has demonstrated a high degree of expression of killifish CFTR (kfCFTR) in the posterior intestine (Singer et al., 1998), consistent with this model, but the function(s) of CFTR in the intestine of teleosts is unknown. Previous studies with fish have not observed ion or fluid secretion by the intestine in spite of numerous attempts (Field et al., 1980; Loretz, 1987a,b, 1995). This lack of secretion has been associated with the absence of crypts of Lieberkühn from teleosts (Loretz, 1987a). Killifish live in estuaries and are detritus feeders that are therefore likely to encounter endotoxin-producing bacteria and, in polluted estuaries, xenobiotic toxins. If secretory diarrhoea is of selective advantage in purging the intestine of endotoxin-producing bacteria, then estuarine teleosts (indeed all coelomates with peristaltic alimentary tracts) ought to have this capability.
Killifish are a model for the osmoregulatory physiology of teleost fish, and much is known about their ion regulation by the mitochondria-rich chloride cells of the gill and opercular epithelium (Karnaky, 1998; Wood and Marshall, 1994; Marshall and Bryson, 1998; Singer et al., 1998). Very little is known about intestinal function in ion and osmoregulation by this species. Classical work by Babkin and Bowie (1928) examined enzyme activities and the operation of the intestine and gallbladder during feeding; these workers found that the alimentary canal is stomachless (as is true for all Cyprinodontidae) and that the chyme is at approximately neutral pH. The killifish intestine is known to be involved in the uptake of toxins and in detoxification. The insecticide DDT accumulates in the intestine (Crawford and Guarino, 1976), and the intestine abundantly expresses cytochrome P450 isoforms that are important in detoxification (Oleksiak et al., 2000). The intestine also absorbs bile salts via a Na+-dependent secondary active transport system (Honkanen and Patton, 1987). However, NaCl and fluid transport and their control have not been studied.
We therefore sought to examine ion and fluid transport by killifish intestine by using combinations of pharmaceuticals that might evoke intestinal secretion. Particularly, we used ionomycin, a Ca2+ ionophore that is more effective in poikilotherm preparations than is ionophore A23187 (Marshall et al., 1993). Ionomycin has been used previously with teleost intestinal preparations (O'Grady et al., 1988; O'Grady, 1989) but not specifically to test for ion and fluid secretion. Ionophore A23187 has inhibitory effects on ion transport by the goby (Gillichthys mirabilis) intestine, but by itself does not produce secretion (Loretz, 1987b).
Materials and methods
Adult killifish (mummichogs, Fundulus heteroclitus L.) of both genders (5–9 g) were captured in Antigonish estuary, transferred to indoor holding facilities and adapted to brackish water (salinity 3 g l–1) at 20–25°C and ambient photoperiod under artificial light for at least 10 days. Fish were tranferred to full-strength sea water (salinity 32 g l–1) or dechlorinated fresh water and acclimated for at least 2 weeks before experimentation. They were fed marine fish food blend (Nutrafin flakes and tubifex worms; R. C. Hagen, Montreal, Canada) at 1 g 100 g–1 body mass day–1, supplemented twice weekly with frozen brine shrimp.
Intestinal preparation
Killifish were anaesthetized in 0.2 g of ethyl 3-aminobenzoate, methane sulphonic acid salt (MS-222) in 1 l of isotonic saline (0.9 g l–1 NaCl), with the pH of the anaesthetic solution adjusted to 6.5–7.5, before being killed by decapitation. The posterior portion of the intestine was dissected, i.e. the section from the anus cephalad to the point where the diameter increases just posterior to the first intestinal loop, which approximates the ileum and jejunum together but excludes the duodenum. Some preparations came from fish that had been starved overnight and killed just before the morning feeding, while others had been fed in the hour prior to the experiment. The intestine section was rinsed inside with Cortland's saline, then ligatured at one end around a polyethylene tube (PE50 tubing; i.d. 0.58 mm, o.d. 0.97 mm). A second ligature closed the bag preparation, and the bag was filled by syringe with Cortland's saline to a steady-state hydrostatic pressure, measured as a column of water connected to the tubing, of 10 cmH2O (approximately 7 mmHg or 0.9 kPa). The tube was then plugged, and the preparation placed in well-stirred and oxygenated Cortland's saline.
The intestinal preparation was removed from the incubation solution, blotted dry and weighed every 10 min, and the mass was recorded. Loss of mass indicated fluid absorption, while gain of mass indicated secretion into the lumen. A control period of 1 h established the absorption rate, after which 1 μmol l–1 ionomycin + 0.5 mmol l–1 dibutyryl-cyclic AMP (db-cAMP) + 0.1 mmol l–1 3-isobutyl-1-methylxanthine (IBMX) was added to the bath, and weighings were continued for a further 2 h. At the end of the experiment, the intestine ligatures were cut off, the preparation was emptied, wet mass was measured and the preparation was cut lengthwise and flattened to measure the surface area. The rate of fluid transport (Jv) was measured as the slope of a least-squares linear regression of mass on time for the control and test periods, each regression comprising at least seven sequential measurements; data were expressed as ml cm–2 h–1.
Flat in vitro preparation
The intestine was dissected as above and divided into two pieces, and each piece was cut lengthwise using artery scissors and mounted over a 0.125 cm2 round aperture. The epithelium was pinned out over the aperture with the rim area lightly greased and bevelled to minimize edge damage. The tissue was stretched gently to the extent that the villi were distinct (not bunched) so that saline could effectively stir the transporting surface. Any adherent mucus was rinsed away, and the intestine was mounted in a modified Ussing chamber so that transmembrane electrophysiological variables could be monitored: Vt, transepithelial potential (in mV; mucosal side ground), Gt, transmembrane conductance (in mS cm–2), and Isc, short-circuit current (in μA cm–2). Isc is expressed as positive for the secretion of anions. Epithelia were clamped to 0 mV except for short periods to record Vt. A current-voltage-clamp (D. Lee Co., Sunnyvale, CA, USA, or WP Instruments DVC 1000) measured epithelial variables.
Radioisotopic fluxes were measured on paired intestinal pieces from a single animal. Radioactive chlorine (36Cl, 0.04 MBq ml–1; NEN Life Science, Boston, MA, USA) was added as the neutral salt and the epithelia were left to equilibrate for 1 h. Samples from the non-radioactive side (225 μl from the 4.0 ml hemichamber) were taken at 20 min intervals, mixed with a scintillation cocktail (Optifluor, United Technologies Packard, Downer's Grove IL, USA) and counted (Packard 2000CA liquid scintillation system) to 1 % error. Samples from the more radioactive side (50 μl) were taken initially and at the end of each hour of the experiment. The control period consisted of three flux periods (of 1 h), after which the test periods (hours 1 and 2) included three flux periods each. Radioisotope fluxes are expressed as μequiv cm–2 h–1.
Bathing solutions
A modified Cortland's saline (305 mosmol kg–1, pH 7.8) was used to bathe both membrane surfaces symmetrically; its composition was (in mmol l–1): NaCl, 160.0; KCl, 2.6; CaCl2, 1.6; MgSO4, 0.9; NaHCO3, 17.9; NaH2PO4, 3.0; and glucose, 5.6. The saline had a pH of 7.8 when equilibrated with a 99 % O2/1 % CO2 gas mixture. Both sides of the membrane in the Ussing chamber were bubbled with the gas mixture, and the outside of the bag preparations was also continuously bubbled.
The primary antibody to detect CFTR was mouse monoclonal anti-hCFTR (R&D Systems, Minneapolis, MN, USA) with the known epitope of (-dtrl), the carboxy terminus of human CFTR (hCFTR). Killifish CFTR has the same carboxy terminus (Singer et al., 1998) and, thus, is selective for this protein. The primary antibody against the Na+/K+/2Cl– cotransporter was mouse monoclonal anti-human Na+/K+/2Cl– cotransporter (NKCC) (Lytle et al., 1995) (Iowa Hybridoma Bank, University of Iowa, Iowa City, IA, USA), an antibody that reacts readily with the Na+/K+/2Cl– cotransporter from a wide variety of species. The primary antibody for Na+/K+-ATPase was mouse polyclonal anti-Na+/K+-ATPase α-subunit from chicken (antibody α-5; Iowa Hybridoma Bank, University of Iowa, Iowa City, IA, USA), an antibody with wide applicability in vertebrates and invertebrates (Lebovitz et al., 1989), including teleost fish (Wilson et al., 2000). The secondary antibody was goat polyclonal anti-mouse IgG conjugated to an Oregon Green 488 fluorophore (Molecular Probes, Eugene, OR, USA), chosen because of the stability and reliability of this antibody.
Whole intestines were fixed overnight in a formaldehyde-free 80 % methanol/20 % dimethyl sulphoxide (DMSO) fixative at –20°C. The methanol was used as a dehydrating agent and the DMSO as a cryoprotective agent. Intestinal pieces were then embedded in embedding medium (Cryogel; S.P.I. Supplies West Chester, PA, USA) and sectioned at a thickness of 10 μm. Sections were fixed for an additional 3 h in 80 % methanol/20 % DMSO at –20°C and rinsed in rinsing buffer (TPBS) consisting of 0.1 % bovine serum albumin (BSA)/0.05 % Tween 20 in phosphate-buffered saline (PBS, composition in mmol l–1: NaCl, 137; KCl, 2.7; Na2HPO4, 4.3; KH2PO4, 1.4; pH 7.4). They were then blocked with 5 % normal goat serum (NGS)/0.1 % BSA/0.05 % TPBS, pH 7.4, for 30 min at 25°C and incubated in the primary antibody (8 μg ml–1 in 0.5 % BSA in TPBS) overnight at 4°C. Sections were rinsed three times and exposed to the secondary antibody (diluted 1:50 in 0.5 % BSA in PBS) for 5 h at 4°C. They were then rinsed three times and incubated with Mitotracker Red (Molecular Probes, Eugene, OR, USA; 100 nmol l–1 in PBS) for 2 h at room temperature. After three final rinses, the sections were mounted in mounting medium (Geltol; Immunon Thermo Shandon, Pittsburgh, PA, USA). Control slides were prepared in a similar manner but had the first or second antibody step eliminated.
Four different animals were used for each antibody. In most cases, paired sections were used in control procedures and the two antibody treatments. Slides were viewed in single blind fashion and images were collected with a laser confocal microscope (Olympus FV300); there was no detectable 'bleed-through' between the red and green confocal fluorescence channels. The false colour for areas that are positive for Mitotracker Red and Oregon Green 488 appears yellow.
Western blots
Intestine and gill filaments, scraped from the arch with a razor blade, were homogenized in ice-cold SEI buffer (300 mmol l–1 sucrose, 20 mmol l–1 EDTA, 100 mmol l–1 imidazole, pH 7.4) using a homogenizer. Homogenates were centrifuged at 2000 g for 6 min. The pellet was resuspended in 2.4 mmol l–1 deoxycholate in SEI buffer and centrifuged a second time at 2000 g for 6 min. The total protein content of the resulting supernatant was determined using the Bradford method (Bradford, 1976).
Proteins were separated on a 7 % polyacrylamide gel using a Mini-Protean 3 Cell system (Bio-Rad, Mississauga, Ontario, Canada). In total, 20 μg of protein was loaded and run for 30 min at 200 V. Proteins were then transferred to a Immobilon-P membrane (Millipore, Bedford, MA, USA) for 2 h using a Mini-Trans-Blot Cell (Bio-Rad). Blots were dried at 37°C for 1 h, stained with Ponceau S and destained with 90 % methanol/2 % acetic acid to visualize the lanes and the molecular mass markers. Blots were then blocked in 3 % bovine serum albumin (BSA)/TTBS (0.05 % Tween 20 in Tris-buffered saline: 20 mmol l–1 Tris-HCl, 500 mmol l–1 NaCl, 5 mmol l–1 KCl, pH 7.4) for 2 h at room temperature on a shaker.
The blocking buffer was poured off, and the blots were incubated with the primary antibody solution [anti-hCFTR monoclonal antibody (R&D Systems, Minneapolis, MN, USA), 1 μg ml–1 in 1 % BSA/TTBS] for 2 h at room temperature. Following a 5 min wash in TTBS buffer, the membranes were incubated with the secondary antibody solution [biotin-SP-conjugated AffiniPure goat anti-mouse IgG (Biochem Scientific, Mississauga, Ontario, Canada), diluted 1:8000 in 1 % BSA/TTBS] for 1 h at room temperature. After being washed in TTBS, the blots were incubated for 1 h with an alkaline-phosphatase-conjugated Streptavidin solution (Biochem Scientific) diluted 1:1000 in 1 % BSA/TTBS. Bands were visualized by incubating the blots in a BCIP/NBT Blue substrate development solution (Sigma, Oakville, Ontario, Canada).
Ionomycin (Calbiochem) was dissolved in DMSO and delivered to the serosal bath at a final concentration of 1 μmol l–1. Dibutyryl-cyclic-AMP (db-cAMP; Sigma) and 3-isobutyl-1-methylxanthine (IBMX; Sigma) were dissolved in a minimum of DMSO (1 mg in 30 μl), diluted in saline and added to the serosal side to final concentrations of 0.5 mmol l–1 and 0.1 mmol l–1, respectively. Addition of vehicle alone (DMSO, final concentration 0.5 % v/v) was without effect (see Fig. 1).
Statistical analyses
Data are expressed as the mean ± 1 s.e.m. The minimum level of significance is P<0.05 on a two-tailed test. Fluid transport data slopes (=flux rates) were established by least-squares linear regression of fluid flow against time. The fluid flux rates were analyzed by two-way analysis of variance (ANOVA) followed by a Bonferroni post-hoc test. Ion flux data were analyzed by one-way ANOVA followed by a Bonferroni post-hoc test. Anterior versus posterior section data of electrophysiology in the two portions of the intestine were analyzed by paired two-tailed t-test.
Fluid absorption and secretion
Killifish intestine has a thin musculature (measured in frozen histological sections to be 100–200 μm fully contracted), so whole tissue bag preparations operate very well without stripping of the musculature. The least disturbance was also gained by not inverting the intestine; hence, experiments proceeded with non-inverted bag preparations with identical Cortland's saline on both sides. Preliminary experiments with dilute solutions in the lumen produced a non-linear time course of fluid absorption, presumably because of a change in the osmotic driving force over time. Preparations with saline on both sides had a linear and easily reproducible rate of fluid absorption. Control tissues with Cortland's saline on both sides showed net absorption of fluid and established a steady-state trend line of loss of mass from the preparation in the first hour of incubation; this rate was unchanged over the 3 h incubation (Fig. 1A). The addition of ionomycin + db-cAMP + IBMX on the serosal side produced net fluid secretion in the preparations (P<0.01; Bonferroni post-hoc test following one-way ANOVA, P=0.005, N=8), while addition of drug vehicle to the contol membranes had no effect (Fig. 1). This secretion was against the small transmembrane hydrostatic pressure gradient of approximately 7 mmHg (0.9 kPa), the steady-state pressure needed to hold saline in the intestinal lumen.
Electrophysiology and ion fluxes
Because the effects of the drug were most clear in fed animals (Fig. 1), ion fluxes were measured on intestinal preparations from fed animals, and because of similar responses from anterior and posterior sections of intestine (see below, Fig. 5), the two sections are considered together. The combination ionomycin + db-cAMP + IBMX increased Gt and Isc within 10 min, and new steady-state values were reached in approximately 45 min (Fig. 2A). These levels were maintained during the second hour of flux data collection (not shown in Fig. 2A). There were significant increases in unidirectional fluxes of Cl– (P<0.05, hour 1 versus control; P<0.001, hour 2 versus control, Bonferroni post-hoc test following one-way ANOVA, P<0.0001, N=7), but the net flux, which was 2.25±0.63 μequiv cm–2 h–1 in the absorptive direction in the control period, changed to secretion of –3.81±1.22 μequiv cm–2 h–1 and –3.15±1.62 μequiv cm–2 h–1 for the first (P<0.05 compared with control) and second (P<0.05 compared with control) hours of drug treatment, respectively. Addition of the anion channel inhibitor DPC (1 mmol l–1) to the apical side significantly reduced Gt, Isc and Cl– efflux (P<0.001, Bonferroni test, N=7 for fluxes, N=14 for electrophysiology) compared with the previous period, reduced Cl– net flux (P<0.05, Bonferroni test) and restored the absorptive Cl– net flux to previous levels 2.67±1.25 μequiv cm–2 h–1 (Fig. 2B, P>0.05, DPC period versus control, Bonferroni test). Gt returned to control levels, while Isc was still significantly elevated (P<0.001, Bonferroni test, N=14) compared with the control period.
A second series of membranes was exposed to ionomycin +db-cAMP + IBMX, as before, but instead of DPC, 100 μmol l–1 DIDS (a blocker of anion exchange and ClC-type anion channels but not of CFTR-like channels) was added to the mucosal bath (Fig. 2C). In this case, there was no reversal of Isc or Gt by DIDS, the unidirectional efflux of Cl– was unchanged (P>0.05, Bonferroni test after ANOVA, P<0.001, N=7 for fluxes, N=14 for electrophysiology) and the secretory net flux of Cl– was maintained (P>0.05, control versus DIDS period, Bonferroni test, N=7).
In an attempt to distinguish the roles of cyclic AMP from that of intracellular Ca2+, a third series was initiated with the addition of only db-cAMP + IBMX (no ionomycin) (Fig. 3). In this case, drug treatment increased in Gt and Isc as before and in a manner essentially indistinguishable from the combined treatment (compare Fig. 3A and Fig. 2A). However, db-cAMP + IBMX tended to increase net Cl– reabsorption, and absorption was 5.39±1.11 μequiv cm–2 h–1 after 2 h (as opposed to the net secretion observed in Fig. 2B). The increase in Cl– efflux was present (P<0.001 compared with control, Bonferroni test) but was less marked than in the first series (compare Fig. 2B and Fig. 3B), suggesting that the Ca2+ ionophore may have been responsible for some of the increase in Cl– efflux and the production of net ion and fluid secretion.
In a fourth series, the addition of ionomycin alone produced no change in Gt and only a transient increase in Isc (Fig. 4A) and Vt (data not shown). There were also no significant changes in the unidirectional and net Cl– fluxes with ionomycin alone; there was instead a small absorptive Cl– net flux (Fig. 4B). Subsequent addition of db-cAMP + IBMX rapidly increased Gt and Isc (Fig. 4A) in association with large increases in unidirectional Cl– fluxes (P<0.01 for Jms and Jsm in hour 2 of treatment compared with the ionomycin period, Bonferroni test following one-way ANOVA, P<0.001, N=7) and a net secretion of Cl–, as seen in the first series (Fig. 4B).
In the flux experiments, we recorded which preparation came from the most posterior section of the intestine compared with the adjacent section immediately anterior and randomized the assignment of unidirectional fluxes between the two sections (Fig. 5). There was no significant difference between the two regions in the Isc of control or ionomycin + db-cAMP + IBMX stimulated membranes (measured in each series and one indicative of combined ion transport; P>0.05, paired two-tailed t-test, N=7), indicating that the two sections were apparently similar in their basal rates of transport and in their reactions to the drugs. For this reason, unidirectional fluxes were combined for the two sections.
Regression of unidirectional Cl– fluxes on Gt (Fig. 6) for the same tissues gave a linear relationship (r2=0.669, slope 0.345±0.033 μequiv mS–1 h–1, mean ± s.e.m., N=55, P<0.001) and a y-intercept that was not significantly different from zero (–0.91±0.97 μequiv cm–2 h–1, mean ± s.e.m., 95 % confidence interval –2.85 to +1.03 μequiv cm–2 h–1). The regression included data from control membranes and from membranes that were stimulated by ionomycin + db-cAMP + IBMX. The linear relationship and zero intercept suggest that most of the ion flux across the tissue was conductive and not via electrically silent transport systems.
For immunocytochemistry of 108 intestine cryosections from 15 fish, we used the mouse monoclonal anti-hCFTR antibody. This antibody has an epitope at the C-terminal end (-dtrl) that is the same in hCFTR and kfCFTR. Sections treated with anti-CFTR and goat anti-mouse IgG-Oregon Green 488 had positive fluorescence localized to the basal portion of the cells and not in the brush-border membrane of most enterocytes (Fig. 7A,B), but in approximately 20 % of sections and in some enterocytes interspersed among the majority there was CFTR-positive fluorescence in the brush border as well as the basal portion of the cell (Fig. 7C,D). We did not observe a difference in apical CFTR immunofluorescence between the tips of villi or in the grooves between villi (analogous to the location of crypts).
We treated 18 intestinal preparations with IBMX and ionomycin for 2 h prior to fixation, but did not observe a change in the cellular distribution of CFTR compared with 18 paired control intestines incubated without drug. This included tightly matched preparations in which the frozen sections of test and control intestine pieces came from the same cut end of the same intestine. The red fluorescence is Mitotracker Red, which, when added after fixation, provided a general (relatively non-specific) counterstain that included mitochondria but also stained brush-border membrane (Fig. 7, see also Figs 9, 10). Western analysis confirmed that the anti-CFTR antibody cross-reacts specifically with discrete protein bands in gill and intestinal tissue but is absent from heart (Fig. 8). The band at 175 kDa is approximately the size expected for CFTR protein. The lower-molecular-mass bands may be splice variants since northern analysis of gill tissue also indicates lower-mass hybridizing bands (Singer et al., 1998).
In 24 intestinal cryosections from five fish stained with mouse anti-human NKCC, with goat anti-mouse IgG Oregon Green 488 as secondary antibody, staining was distributed across the cytoplasm but not in the nuclei or in mucous cells (Fig. 9A,B). Unlike CFTR immunostaining, in most cases (approximately 80 % of sections) there also was significant staining of the brush-border region of the majority of enterocytes (Fig. 9C,D).
Immunofluorescence of nine cryosections from three fish using a polyclonal antibody to Na+/K+-ATPase α-subunit indicated positive reactions outside the nuclei of the enterocytes and in the basal approximately two-thirds of the cells. There was no significant staining of the dermal portions of the villi or of the apical portion of the cytoplasm and the brush-border membrane of enterocytes (Fig. 9E,F). The observed distribution of transporters is consistent with an absorptive mode of transport with Na+/K+-ATPase in the basolateral membrane, NKCC at the apical membrane (in part) and CFTR anion channels at the basal and lateral membranes in most enterocytes. A second group of enterocytes has CFTR in the apical membrane and, in combination with basolateral NKCC and Na+/K+-ATPase, could secrete Cl– (and fluid).
Control sections stained with Mitotracker Red and the second antibody but lacking the primary antibody had no green fluorescence, indicating the absence of non-specific binding of the second antibody and the absence of 'bleed-through' from the red channel (Fig. 10). Control sections treated with the primary antibody but without the secondary antibody also demonstrated no detectable fluorescence (not shown).
Induction of intestinal secretion
Normally, the intestine of marine teleosts absorbs NaCl and fluid (for a review, see Loretz, 1995), and there is progressive reabsorption along the intestine of Na+, Cl– and K+ but not of Mg2+ or SO42–. The evidence suggests ion uptake either by Na+/K+/2Cl– cotransport in the apical membrane, as in seawater-adapted flounder (Platichthys flesus) (for a review, see O'Grady et al., 1987), or possibly via Na+/Cl– cotransport, again as in flounder (Halm et al., 1985; Grosell and Jensen, 1999), or by parallel antiporter mechanisms, as in Oreochromis mossambicus (Howard and Ahearn, 1988). Ca2+-activated K+ channels and a voltage-sensitive anion channel (with properties clearly different from those of CFTR) are located in the basolateral membrane of teleost intestine (Loretz and Fourtner, 1988). The anion channel is the likely pathway for Cl– exit during NaCl absorption (Loretz, 1995).
In teleost intestine, it appears that, for all species studied, ion reabsorption mechanisms have been universally observed. Loretz (1987a) suggests that teleosts have secondarily lost the ability to secrete NaCl and fluid while tetrapods and elasmobranchs retain this secretory ability. Tetrapods secrete ions and fluid intestinally, associated with the crypts of Lieberkühn, while elasmobranchs secrete ions into the intestinal lumen via the rectal gland (an outpocket of the posterior intestine). In elasmobranchs and tetrapods, ion secretion is initiated by cyclic AMP and agents that increase cyclic AMP levels (Loretz, 1987b; Valverde et al., 2000). Our results indicate that the killifish intestine can indeed be made to secrete ions with the additional stimulus of an efficient Ca2+ ionophore. Hence, it is clear that the intestines of lower vertebrates, including those of teleost fish, can be secretory (contrary to previous information) and do not rely upon crypts or specific outpocketing structures to produce the response because killifish intestine lacks these structures. One explanation is that the crypts of Lieberkühn in mammals, which are associated with intestinal secretion, harbour enterocytes capable of secretion, but in teleosts the secretory enterocytes, which possess apical CFTR channels, are interspersed among other absorptive cells with similar microscopic appearance.
The killifish intestine has a small negative transepithelial potential (–0.4 to –0.6 mV) and a low transepithelial resistance of 50–100 Ω cm2 typical of many marine teleosts (see Table I in Loretz, 1995) but unlike the high-resistance goby intestine or the positive potentials of freshwater salmon intestine. On the basis of Isc measurements of resting and stimulated tissues, we found no difference between the most posterior sections of the intestine in the last 3–4 cm of the intestine; however, there is recognized functional zonation of anterior versus posterior intestine (Loretz, 1995). We did not examine more anterior portions of the killifish intestine, but instead restricted our examination to the zone in which we had previously demonstrated CFTR expression (Singer et al., 1998). The fluid absorption rates we observed under control conditions (+18.9±8.3 μl cm–2 h–1N=8, Fig. 1) were lower than those observed previously in seawater eel (Anguilla japonica) intestine: 92.4±7.8 μl cm–2 h–1 (Uesaka et al., 1994) and 42.9±3.1 μl cm–2 h–1 (Ando, 1983). The eel intestine has a larger transepithelial potential and transepithelial resistance but approximately similar Cl– net flux compared with seawater killifish intestine (killifish, control periods in Figs 2B, 3B, 4B; eel, 2.51±0.12 μmol cm–2 h–1, N=7) (Uesaka et al., 1994). The difference in fluid transport rates could be ascribed to species differences, since eel and killifish are evolutionarily distant from each other, or to different measurement techniques (e.g. the thicker eel intestine requires stripping of the muscularis).
The linear relationship between Cl– fluxes and conductance suggests that most of the ion flux across the tissue was conductive and not via electrically silent transport systems. It is likely that some of the Cl– flux is transcellular because, in goby posterior intestine, regression of radiochloride efflux on tritiated mannitol flux (a paracellular pathway tracer) has a positive intercept (Mooney and Loretz, 1987). These facts point indirectly to the involvement of Cl– channels in transepithelial Cl– transport in the intestine and support a role for CFTR.
Ca2+ effects
Teleost intestine possesses a Ca2+ calmodulin inhibition of NaCl absorption (Loretz, 1987b) that can be initiated by the Ca2+ ionophore A23187 (1 μmol l–1) and blocked by the calmodulin antagonists trifluoperazine and calmidazolium (R24571, 0.1 mmol l–1). However, the inhibitory effect of IBMX was also present (Loretz, 1987b). It is likely that the ionomycin response observed here was connected with intracellular Ca2+ mediation in that ionomycin has been shown not to elevate intracellular cyclic AMP or cGMP levels in flounder intestine (O'Grady, 1989) and the ionophore inhibits Na+ and Cl– absorption by a pathway independent of cyclic nucleotides (O'Grady et al., 1988). The killifish intestine exposed to ionomycin showed a non-significant trend towards a decrease in Cl– absorption in the first hour of treatment. It is clear that Ca2+ stimulation alone cannot eliminate absorption completely or produce net secretion; this is consistent with the traditional view that Ca2+ signalling in the vertebrate intestine is 'antiabsorptive' (Powell, 1986).
The value of intestinal secretion
The phenomenon of intestinal secretion in certain pathological conditions is presumably of selective advantage to the animal in purging the intestinal lumen of some or all of an infectious or toxic agent. No previous researchers have investigated the possibility of combined Ca2+ and cyclic AMP signals being required to elicit intestinal secretion. The combination of ionomycin + db-cAMP + IBMX evokes secretion of Cl– and fluid that develops in the first hour of treatment and is sustained thereafter. Ionomycin alone and db-cAMP + IBMX alone were ineffective in producing net Cl– efflux or net fluid secretion. The main function of cyclic AMP seems to be to increase total tissue conductance since ionomycin had no effect on this variable. The present data are consistent with the suggestion that cyclic AMP opens paracellular pathways in the intestine (Bakker et al., 1993). However, in the absence of ionomycin, cyclic AMP increased unidirectional Cl– fluxes and Gt but did not change the net flux, so ionomycin in the combined response appears to mediate the rapid increase specifically in the unidirectional Cl– efflux. Hence, the combination of Ca2+-stimulated transcellular Cl– efflux linked with cyclic-AMP-mediated increases in paracellular conductance may allow transcellular ion (NaCl) secretion to drag solute osmotically, resulting in the observed fluid secretion.
Role for CFTR
The inhibition of Cl– efflux by DPC (8.7 μequiv cm–2 h–1) is larger than the decrease noted in the corresponding Cl– influx (2.8 μequiv cm–2 h–1) and is accompanied by a large (12 mS cm–2) decrease in Gt, consistent with an action of DPC on anion channels in the apical membrane. DIDS, a blocker of the anion exchanger and of some volume-sensitive anion channels (but not CFTR), had no effect on Gt, Isc or the net Cl– flux. In the chloride cells of the opercular epithelium, CFTR-like channels are activated by cyclic AMP (Marshall et al., 1995). kfCFTR is expressed in killifish intestine (Singer et al., 1998) (northern blot analysis). The results are compatible with the idea that CFTR-like anion channels in the apical membrane of the intestine are activated by cyclic AMP and are responsible for the increase in Cl– efflux and the development of net Cl– secretion.
The presence of CFTR immunofluorescence in the apical membrane of some enterocytes and the basal distribution of NKCC and Na+/K+-ATPase in most enterocytes is a pattern expected for cells contributing to NaCl secretion (Fig. 11). From the sections observed, it seems that perhaps 10–20 % of sections have apical staining for CFTR, and the distribution appears patchy. The distribution is similar to the pattern seen in mitochondria-rich cells of the gills of the mudskipper Periophthalmodon schlosseri (Wilson et al., 2000). The presence of NKCC immunofluorescence in the basal and apical portions of many enterocytes implies that, functionally, NKCC may be activated differentially to produce the effect of uptake (apical NKCC activated) or secretion (basal NKCC activated) (Fig. 11). Because CFTR appears to be present in the apical membrane of some cells, there may be a subpopulation of enterocytes responsible for ion (and fluid) secretion. The rapidity of the change to fluid secretion observed in the intestine is consistent with previous observations of rapid cyclic AMP activation of CFTR in opercular membranes (Marshall et al., 1995) and by CFTR expressed in amphibian oocytes (Singer et al., 1998).
The present data, i.e. the apparent lack of redistribution of CFTR immunofluorescence in response to treatment with IBMX and ionomycin, also confirm the observations that cyclic AMP (via protein kinase A and phosphorylation) activates CFTR already in situ in plasma membranes, rather than acting by regulating trafficking of CFTR to the membrane (Moyer et al., 1998; Loffing et al., 1998). There remains the possibility of the involvement of other anion channels in Cl– uptake, including members of the ClC family known to be involved in Cl– secretion in mammalian intestine (Gyomorey et al., 2000) and the voltage-sensitive anion channel in teleosts (Loretz and Fourtner, 1988); hence, CFTR appears to contribute to Cl– uptake and secretion in the teleost intestine.
Composition of secreted fluid
The measured absorption of ions and fluid allows the approximate concentration of the transported fluid to be calculated. If one averages the observed control period Cl– net flux values (from Figs 2B, 3B and 4B: 2.5, 2.7 and 2.3 μequiv cm–2 h–1) and divides by the fluid transport rate (control period, Fig. 1, 18.4 and 18.3 μl cm–2 h–1), the calculated concentration is 2.5 μequiv cm–2 h–1/8.4 μl cm–2 h–1= 136 mmol l–1 Cl–. Given that plasma [Cl–] for seawater Fundulus heteroclitus is approximately 165 mmol l–1, then the absorbate is approximately at the isoionic/iso-osmotic level. Performing a similar calculation for the secreted fluid (net ion fluxes from drug treatment periods of Figs 2B and 4B; 3.8, 3.3, 3.80 and 2.8 μequiv cm–2 h–1 and fluid secretion of 7.4 μl cm–2 h–1 in Fig. 1) produces an effective concentration of the secreted fluid of 3.4 μequiv cm–2 h–1/7.4 μl cm–2 h–1= 460 mmol l–1 Cl–, which is decidedly hypertonic because Na+ will follow the secretion of Cl– to maintain electroneutrality. This suggests that marine fish that drink full-strength sea water could absorb ions and fluid in the anterior intestine and (pathophysiologically) secrete a fluid of similar composition to sea water in the posterior intestine. The estimate also suggests that the ion secretion activated by the drug treatment opens a pathway for Cl– secretion that is transcellular and poorly connected with the osmotic permeability of the whole system; hence, the secreted fluid appears to be hypertonic. The notion of transcellular Cl– secretion fits our data in that the activation of apical membrane ion channels for ion secretion in a membrane lacking water channels could initiate ion secretion without efficient osmotic water flux, thus producing secretion of a concentrated fluid, as observed.
Function and endogenous regulation of secretion
The function of intestinal secretion in fish is unknown, but it presumably aids in purging toxic intestinal bacterial flora. If such intestinal secretion occurs normally or pathophysiologically in fish, estuarine animals would not suffer the dire dehydration and demineralization that terrestrial tetrapods do. Indeed, it would be reasonable for estuarine animals to respond to this osmoregulatory stress simply by behaviourally seeking iso-osmotic environments (sea water or brackish water) that could be consumed and absorbed in the anterior sections of the gut to replace both fluid and ions in appropriate amounts during bouts of intestinal secretion. In this way, intestinal secretion could be of selective advantage, particularly in estuarine fish.
The question remains open as to whether a combination of endogenous hormones might evoke intestinal secretion in teleosts. It is curious that secretion was evoked more clearly in fed animals, suggestive of a hormonal priming of solute transporters by feeding. Atrial natriuretic peptide (ANP), mediated by cyclic GMP, inhibits Na+/K+/2Cl– cotransport in the flounder intestine (O'Grady et al., 1985). Acetylcholine and serotonin also inhibit NaCl and water reabsorption (Uesaka et al., 1994; Trischitta et al., 1999), an effect antagonized by somatostatin-related peptides. In turn, the actions of somatostatin and analogues in the goby intestine appear to be via a natural receptor that more readily accepts another endogenous hormone, urotensin II, which is somatostatin-like (Loretz et al., 1983; Loretz, 1990). In goldfish (Carassius auratus) intestine, vasoactive intestinal polypeptide (VIP) and serotonin may inhibit NaCl reabsorption by an action reducing tight-junctional selectivity (Bakker et al., 1993). This hypothesis was supported by the action of cyclic AMP on tight junctions in eel (Anguilla anguilla) intestine (Trischitta et al., 1996). Serotonin inhibits NaCl reabsorption, and its action is mediated via adenyl cyclase (Bakker et al., 1993). Whereas ANP in flounder intestine increases intracellular cGMP levels (O'Grady, 1989), VIP apparently acts via cyclic AMP in flounder (O'Grady, 1989) and in goldfish (Bakker et al., 1993) intestine. ANP and VIP were hypothesized to be released by enteric nerves and to act locally (O'Grady, 1989), and this localization has been definitively demonstrated by fluorescence immunocytochemistry (Loretz et al., 1997).
Urotensin II stimulates NaCl reabsorption in goby intestine via a lowering of intracellular Ca2+ levels (Loretz and Assad, 1986). The Ca2+ ionophore A23187 produces a marginally significant (Loretz, 1987a,b) or no effect on intestinal preparations (Bakker et al., 1993), but this lack of a clear response may be ascribed to the low efficiency of this ionophore compared with ionomycin. For instance, killifish opercular epithelium Cl– secretion is inhibited by ionomycin but not by the Ca2+ ionophore A23187 (Marshall et al., 1993). The high affinity of adrenergic receptors in goldfish intestine for clonidine and blockade by yohimbine indicate the presence of α2-adrenergic receptors (Bakker et al., 1993) and, if the receptors are similar to those in the opercular membrane (Marshall et al., 1993), they too may be mediated by Ca2+ and could activate this pathway in the intestine. Taken together, the endogenous hormones that might produce intestinal secretion would be a combination of serotonin or VIP to activate adenylate cyclase and an α2-adrenergic agonist to activate intracellular Ca2+.
The research is in part the Honours BSc of J.A.H. and was supported by the Natural Sciences and Engineering Research Council of Canada through grants to W.S.M. and USRA scholarships to J.A.H. and a University Council of Research grant to E.M.L. Thanks to A. L. MacDonald for expert animal care and to C. A. Loretz for improvements to the manuscript.


text:
Brass Oil Lamp, Decorative Aarti Diya with Long Handle, Pack of 1.
Nutristar Brass Oil Lamp, Decorative Aarti Diya with Long Handle.
Product Details: The aarti diya has a diya to contain enough oil and wick to burn and a long handle for safe use. Adorn your temples with this Aarti diya which is a must for all religious ceremonies.
Colour: Golden.
Size: Length - 9 Inches.
Package Contains: 1 Brass Aarti Diya.
Benefits: Brass items are being used by humankind for quite some time. Keeping its benefits in mind and with advanced technology, Nutristar made brass oil lamp. It is value for money and investment for a lifetime. Brass in Hindustani is called Pittal or Pital. Humankind has been using it since the primitive age till now.
Usage: The usage is simple; we need to put some oil in the lamp and a cotton wick. Your lamp is ready to light your home. The oil lamp is mainly used to decorate houses and places of worship to resemble positivity and bring harmony.
Cleaning: Brass gets stains if not used often, but it gets easily cleaned up with the help of cotton and oil. After usage, wash the diya with normal soap, the brass base, and the lamp can be cleaned with vinegar and salt. Dry the Diya before keeping it in the cupboard. If not in use, keep the lamp in a place where there is less moisture.
Preservation: Brass is the friendliest metal in the environment and is easy to recycle, making it the greenest natural metal. To make its life longer, always dry them after washing with a cotton cloth and keep them in a dry place.
Legal Disclaimer: As all products are handcrafted, sizes may differ. All the mentioned dimensions and weights are approximate.
Free shipping all over India.
Nutristar uses the best courier in the business to make sure your order gets to you on time. You'll see your item description, price, and delivery date on the Checkout page. Our courier partner does not count Saturdays, Sundays, or Public Holidays in their guaranteed delivery time. Our shipping partners which help us to deliver are DHL, Dtdc, Delhivery, Blue Dart, and many more Local Services.
It will take 2 to 4 days to get your order. If randomly selected by the customs department, it might get delayed.
For International Courier Service:
We are glad that we deliver 3 to 5 International parcels per week. We ship to the USA, Canada, UK, Australia, and Dubai. Our shipping partners which help us to deliver internationally are DHL, UPS, FedEx, and many more Local Services.
It will usually take 6 to 10 days for the parcel to be delivered to the International destination. If randomly selected by the customs department it might get delayed.
The charges for international parcels vary depending on the product you select. Courier service takes parcels with volumetric or weight, whichever is greater.
It is recommended to select more products to reduce courier charges.
If you have any shipping concerns please call or whatsapp us at +91-9652264202 for assistance.
Returns Policy
You may return most new, unopened items within 10 days of delivery for a full refund. We'll also pay the return shipping costs if the return is a result of our error (you received an incorrect or defective item, etc.)..
If you received an item as per your requirement but still want to return the product for some other reasons. For such returns, you have to bear the courier charges.
You should expect to receive your refund within four weeks of giving your package to the return shipper, however, in many cases you will receive a refund more quickly. This time period includes the transit time for us to receive your return from the shipper (5 to 10 business days), the time it takes us to process your return once we receive it (3 to 5 business days), and the time it takes your bank to process our refund request (5 to 10 business days).
If you need to return an item, simply login to your account, view the order using the "Complete Orders" link under the My Account menu and click the Return Item(s) button. We'll notify you via e-mail of your refund once we've received and processed the returned item..

subset: commoncrawl


text:
Seamlessly integrated with your Epicor ERP implementation, BiscitRMS allows you to manage the day-to-day aspects of the equipment hire and rental industry with ease.
BiscitRMS offers a powerful, browser-agnostic web application with an interactive status dashboard for visibility and availability of your hire fleet.
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text:
Argosy Publishing, Inc.,以Visible Body的名称开展经营("公司"或"我们"),从事网络应用程序、桌面应用程序和移动应用程序的开发。公司重视我们应用程序之用户和其他个人("您")的信息和数据的隐私,我们可能会收集与您有关的信息用于识别您(您的"个人信息")。本隐私声明阐述了有关我们收集和使用您的个人信息的政策和做法。如果您不同意本文规定的条款,请不要使用我们的网站或我们的网页版、桌面版和移动版应用程序。我们保留随时更新本隐私声明的权利;并且,以上修订日期为您提供隐私声明已更新的通知。
我们从您收集哪些信息取决于您如何与公司、我们的网站和我们的应用程序进行互动,下文有更详细的描述。 除了下文所述的具体用途之外,我们还可能会将您的个人信息用于我们在遵守法律业务过程中的合法利益,用于执法目的,保护和捍卫我们的权利和财产,或执行我们的用户协议或与第三方达成的协议。
- 联系方式信息(例如:电子邮件地址、电话号码)
- 位置(例如:州/省、国家/地区)
- 机构隶属关系和角色(例如:学生、医护人员)
- 语言偏好设定
- 有关您使用的产品和技术的信息(例如:设备、平台、操作系统)
- 您对开放式问题的回答(例如:您感兴趣的产品或服务类型、您遇到的技术问题、您的建议)
如果我们以其他方式与您联系,我们也可能收集这些信息。 例如,如果您在展会期间造访我们供应商的展台时同意注册加入我们的邮件列表。
- 提供您所请求的服务、产品或信息
- 向您发送我们认为您可能感兴趣的产品和服务的促销资料或通信
- 提供客户服务或协助您解决技术问题
- 评估和/或改进我们所提供的产品和服务,以及开发新的产品或服务
我们是在您同意的情况下发送促销类电子邮件。 当我们向您提供您所请求的服务或信息时,我们这样做是因为这是执行我们的合同或合同之前措施所必需的行动。其他信息处理活动是基于我们的合法利益进行,例如寻求客户反馈和改进我们的产品。
当您访问我们的网站以及我们向您发送营销类电子邮件时,我们会使用cookie和诸如网络信标之类的其他技术来自动收集某些信息。 我们以这种方式收集以下信息:
- 访问来源(例如:您是如何找到我们网站的)
- 某些页面的访问次数以及访问者使用了哪些网页和哪些应用程序的功能
- 你使用的是什么浏览器
- 电子邮件追踪信息(例如您是否打开了我们的电子邮件)
- 帮助改进我们网站和电子邮件的功能和实用性
- 用于对网站用户的行为进行统计性分析
- 用于产品开发和/或内容改进
- 用于按需定制我们网站的内容和布局
我们还使用第三方(例如Google Analytics)来帮助分析用户对本网站的使用情况。 Google为此目的使用了cookie并向我们提供汇总信息。
如果您通过我们的代理商2Checkout或Fastspring之一购买我们的产品,我们会从代理商那里收到有关您购买的某些信息,其中包括联系信息(例如姓名、电子邮件地址)和订单信息(例如帐单邮寄地址、销售来源、付款方式)。 我们将这些信息用于维护我们在为客户提供客户支持过程中的合法利益以及跟踪产品的采购。
Visible Body应用程序的用户
如果您使用我们课程包(Course Pack)的某一产品,我们会收集以下个人信息:
- 电子邮件地址
- 所属的机构
- 激活信息(例如:激活的日期和时间)
Courseware、Web Suite和某些移动应用程序用户的Visible Body帐户
如果您使用了我们的Courseware,Web Suite,人体解剖学图谱+或Visible Body+产品,将会需要您创建Visible Body帐户。此外,我们的某些移动应用程序可能会要求您创建Visible Body帐户,以便共享内容并跨设备访问您的用户创建的内容。在您创建Visible Body帐户时,我们会收集以下个人信息:
- 联系方式信息(例如:姓名、电子邮件地址)
- 登录信息,包括加密的密码
- (仅限Courseware)所属机构、LMS用户ID(如果有)
- (仅限Courseware和移动App)角色(例如:学生或讲师)
- (仅限Courseware和移动App)用户创建内容(例如:测验、截止日期、作业、保存的视图、便笺卡)
- (仅限移动App)App信息和设置(例如:产品名称、产品版本、设备OS、App语言首选项、App内购)
如果您使用Google帐户登录,Google将与Visible Body分享您的姓名、电子邮件地址、语言偏好和个人照片。
我们使用这些信息向您提供产品(Courseware和Web Suite)和由用户创建的内容(Courseware和移动App),以及为了我们在维护产品激活、检查激活状态和监控产品总体使用情况方面的合法利益。
- 我们的供应商和服务提供商,例如,协助公司提供服务、营销、分析、数据存储或内容管理的服务提供商,或向公司提供咨询服务或专业服务的服务提供商
- 执法机关、政府机构或其他主管部门,以遵守法律、法规、法院命令或其他法律义务,或为了保护和维护我们的合法利益
- 如果您通过所属的机构(例如,大学或学院)来使用我们的产品,则会将您的个人信息披露给您所属的机构,以跟踪应用程序的激活并提供包括Courseware在内的学习管理服务(例如,您的姓名、电子邮件地址、测验分数将提供给您的讲师)
- 如果您索取有关我们的经销商或分销商出售的Visible Body产品的信息,会将您的个人信息披露给我们的授权经销商和分销商
公司总部位于美国境内。 我们从您处收集的信息将在美国进行处理。美国并未向欧盟寻求处理您的个人信息的"适当性",也没有收到这一结论。关于从欧盟转移信息,公司依赖于特定情况的减损。特别是,只有在您同意的情况下,或是为了执行与您订立的合同(或是符合您的利益),或是以不超过您的权利和自由的方式来实现公司令人信服的合法利益,公司才会将个人信息转移到美国。公司会努力采用适当的保护措施来保护您的个人信息的隐私和安全,并以符合本隐私声明的方式来使用您的个人信息。公司不收集敏感型数据(即在欧盟被称为特殊类别的数据)。
除非本隐私声明中另有说明,本公司将保留个人信息,并保留到向您提供服务以及此后为遵守我们法律或合同义务所需的时长。 如果我们确定上述目的不再需要保留有关潜在客户的信息,我们会定期删除这些信息。经书面请求或在协议终止后的规定期限后,个人信息将从有效数据库中删除。备份中存储的信息不会被主动清除,而是随着时间自然清理。Visible Body保留个人信息备份的时间不会超过90天。
我们的网站不供13岁以下的儿童使用。 我们不会故意从13岁以下儿童收集个人信息。如果您未满13岁,请勿在本网站上或通过其任何功能使用或提供任何信息(包括您的姓名、地址、电话号码或电子邮件地址)。如果我们获知在未经父母同意的情况下从13岁以下的儿童收集或收到了个人信息,我们将删除这些信息。如果您认为我们可能持有来自13岁以下儿童的或与其相关的任何信息,请立即与我们联系。
本网站含有转到其他网站的链接。 我们对此类其他网站的隐私做法概不负责。我们希望访问者在离开我们的网站时意识到这一点,并阅读收集个人信息的每个网站的隐私政策。除本文另有规定外,本隐私声明仅适用于本网站收集的信息。
Visible Body
492 Old Connecticut Path, Suite 501
Framingham, MA 01701
对于受欧洲数据保护法律管辖的个人信息,Argosy Publishing, Inc.是这些个人信息的控制者。
EEA Privacy Disclosures
These privacy disclosures (the "Disclosures") provide information about the collection, use, processing and sharing of data about individuals located in the European Union, Iceland, Liechtenstein or Norway (the "European Economic Area" or "EEA").
These Disclosures also provide information about the collection, use, processing and sharing of data about individuals located in the United Kingdom, which has left the European Union but has adopted legislation substantially similar to the GDPR. With respect to individuals in the UK, references to the GDPR in these Disclosures are to be read as referring to the UK's similar legislation, the Data Protection Act 2018.
In these Disclosures:
- GDPR means the European Union's General Data Protection Regulation;
- Personal Data means information relating to an identified or identifiable individual; an identifiable individual is one who can be identified, directly or indirectly, by use of any identifier or factor specific to that individual; and
- GDPR Processing Activities means the collection, use, processing or sharing of Personal Data when those activities are within the scope of the GDPR.
These Disclosures apply only to the use of Personal Data in GDPR Processing Activities. In these Disclosures the words "Company," "we," "us" or "our" refer to Argosy Publishing, Inc. d/b/a Visible Body. These Disclosures apply to GDPR Processing Activities by any means, including hardcopy (such as paper applications or forms) and electronic means (such as websites and mobile applications).
A. How We Collect and Use Personal Data
We collect several categories of Personal Data in circumstances that may involve GDPR Processing Activities, including data you provide, data collected automatically (potentially including location data), and data we obtain from third party sources.
We use the Personal Data that we collect to:
- Create and maintain your account;
- Process your account registration;
- Answer your questions;
- Send you newsletters, updates, and other communications that you have requested;
- Send you information about our services and resources; and
- If you use our products through your affiliation with an institution, such as a college or university, coordinate with the institution you are affiliated with, in order to track activation of applications and to provide learning management services.
As described in more detail below, we rely on a number of legal bases to lawfully process your Personal Data.
The ways in which we collect and use your data vary depending on the relationship between you and us. The following sections of these Disclosures describe in more detail how we collect and use Personal Data in various circumstances that may involve GDPR Processing Activities.
Please note that, depending on the situation, some of the processing of Personal Data we do in the various circumstances described below may not fall within the scope of the GDPR.
1. Personal Data We Collect
Websites and Mobile Applications
As is true of most digital platforms, we obtain certain data automatically when you use one of our websites or mobile applications, such as your IP address, browser type and device type. Certain web forms also collect Personal Data you provide, for example when you enter data into form fields, such as for the purpose of registration. If we also process data through our websites or mobile applications for one of the activities described further below, those descriptions will provide additional information about how those data are collected and used. We and our third-party vendors use this Personal Data for the primary purposes of conducting analytics, improving our websites, responding to your requests and providing you with relevant information.
2. Personal Data We Obtain from Third Party Sources
As part of our GDPR Processing Activities, we may obtain certain Personal Data about you from third party sources, which we may use for the purposes and in the ways described in "How We Collect and Use Personal Data" above and in "Additional Uses of Personal Data" below. In some cases, we may obtain your consent for additional uses.
Partners and Service Providers
We use partners and service providers to provide services for us. Some of these partners have access to Personal Data about you that we may not otherwise have (for example, when you sign up directly with that provider) and may share some or all of these data with us.
3. Additional Uses of Personal Data
In addition to the uses described above, including under "How We Collect and Use Information" and "Personal Data We Obtain from Third Party Sources," we may use your Personal Data for the following purposes. These additional uses may under certain circumstances be based on your consent, or may be necessary to fulfill our contractual commitments to you, for legal compliance, or to serve our legitimate interest in the following activities:
- Conducting our operations and administering educational offerings;
- Responding to your requests for research assistance;
- Processing and responding to your requests or inquiries of any other kind;
- Providing you with newsletters, articles, service alerts or announcements, event invitations, and other information that we believe may be of interest to you;
- Conducting research, surveys and similar inquiries to help us understand trends and needs of our Members and customers;
- Performing marketing, promotions and advertising, either directly or through third-parties. These activities may include interest-based advertising, targeted advertising and online behavioral advertising in order to increase the likelihood that the content will be of interest to you;
- Preventing, investigating, taking action regarding or providing notice of fraud, unlawful or criminal activity, other misconduct, security or technical issues, or unauthorized access to or use of Personal Data, our website or data systems; or
- Responding to subpoenas, court orders, or other legal process; enforcing our agreements; protecting the health, safety, rights or property of you, us or others; and meeting legal obligations.
4. Legitimate Interests
In addition to interests otherwise described in these Disclosures, we rely on other legitimate interests in using and sharing your Personal Data. These interests include:
- Providing, improving and customizing our educational offerings;
- Administering our operations;
- Furthering research and understanding in fields of academic study;
- Offering attendance to events and opportunities to participate;
- Understanding how our online platforms are being used;
- Exploring ways to develop and grow our operations;
- Cybersecurity;
- Enhancing protection against fraud, spam, harassment, intellectual property infringement, crime and security risks; and
- Meeting our obligations and enforcing our legal rights.
5. Data Retention
We will retain your Personal Data for as long as is necessary for the purposes set out in these Disclosures and for as long as is required under applicable law or is needed to resolve disputes or protect our legal rights or otherwise to comply with legal obligations. Consistent with the foregoing guidance, some data may be retained indefinitely.
Where we are processing Personal Data based on your consent, we generally will retain the information for the period of time necessary to carry out the processing activities to which you consented, subject to your right, under certain circumstances, to have certain of your Personal Data erased (see "Your Rights" below).
Where we are processing Personal Data based on contract, we generally will retain the information for the duration of the contract plus some additional limited period of time that is necessary to comply with law or that represents the statute of limitations for legal claims that could arise from the contractual relationship.
Where we are processing Personal Data based on the public interest, we generally retain the information for the period of time that continues to serve that underlying interest.
Where we are processing Personal Data based on our legitimate interests, we generally will retain the data for a reasonable period of time based on the particular interest, taking into account the fundamental interests and the rights and freedoms of the data subjects. In some cases, where Personal Data was primarily processed and retained on the basis of consent, contract, the public interest, or other bases described in these Disclosures, we may continue thereafter to retain the data based on a legitimate interest.
B. How We Share and Disclose Personal Data
We share your Personal Data with third parties in the ways described in these Disclosures, including the "How We Collect and Use Personal Data" section above. Additionally, we may share information as described below:
Service Providers
We share your Personal Data with third-party service providers that complete transactions or perform services on our behalf or for your benefit, such as:
- Marketing and analytics;
- Event registration and coordination;
- Providing course platforms or tools that enable or enhance our offerings;
- Research insights and analytics;
- Research collaboration;
- System maintenance and security;
- Facilitating other transactions with you; and
- Assisting with our legal compliance.
Social Media Platforms
We may also use services provided by third parties (such as social media platforms) to serve targeted ads or sponsored content on third-party platforms. For more information regarding our use of cookies and similar technologies, see the "Cookies and Similar Technologies" section below.
Legal Process, Safety and Terms Enforcement
We may disclose your Personal Data to legal or government regulatory authorities as required by applicable law. We may also disclose your Personal Data to third parties in connection with claims, disputes or litigation, when otherwise required by applicable law, or if we determine its disclosure is necessary to protect the health, safety, rights or property of you, us or others, or to enforce our legal rights or contractual commitments that you have made.
C. International Data Transfers
Much of our Personal Data processing takes place in the United States, though sometimes we or third parties with whom we share data, as discussed above, may process data in other countries. The data privacy laws in the United States and other countries outside the EEA and the UK may provide less protection than such laws in the EEA or the UK. In the event we transfer your Personal Data outside the EEA or outside the UK as part of our GDPR Processing Activities, we rely where required on appropriate or suitable safeguards or specific derogations recognized under the GDPR or under UK law.
The European Commission has adopted standard data protection clauses, also applicable in the UK, which provide safeguards for Personal Data transferred outside of the EEA or the UK. We may use Standard Contractual Clauses when transferring Personal Data from a country in the EEA or from the UK to a country outside the EEA or the UK. If so and your Personal Data are affected, you can request a copy of the Standard Contractual Clauses relevant to your Personal Data by contacting us as set forth in the "Contact Us" section below.
D. Cookies and Similar Technologies
We may collect Personal Data about you, or information that becomes Personal Data if combined with other information, when you visit or use our websites and online services. This information may be collected through the use of cookies, which are small data files placed on your computer or mobile device that allow us to collect certain information whenever you visit or interact with our websites or online services. Some of these cookies are managed by us (first-party cookies), while others are managed by third parties that we do not control (third-party cookies). This information may also be collected through the use of other data collection technologies (such as web beacons, pixels or tags) that embed graphic files in our websites and online services. These graphic files contain a unique identifier that enables us to recognize when someone has visited our website or online services, or in the case of web beacons, opened an email that we have sent them.
These small data files or graphic files serve various functions:
- Strictly Necessary: Necessary to deliver our services;
- Performance and Functionality: Enhance the performance and functionality of our services but are non-essential to their use;
- Analytics and Customization: Allow us to understand the effectiveness of our services and marketing campaigns, as well as to customize our services based on this information; or
- Advertising: Make advertising messages more relevant to you and your interests.
You can control the use of certain cookies and similar technologies by:
- Opting out of targeted online advertising through advertising networks (please visit http://www.aboutads.info/choices/, http://optout.networkadvertising.org/ or
http://www.youronlinechoices.com for more information);
- Setting or amending your web browser controls to accept or refuse cookies (please visit your browser's help menu for more information).
If you choose to reject certain cookies and similar technologies, you may still use our websites and online services although your access to some functionality and features may be restricted. If you have any questions regarding our use of cookies and other similar technologies, please contact us as set forth in the "Contact Us" section below.
E. Your Rights
Upon your reasonable, good faith request we will provide you with information about whether we hold any of your Personal Data as part of our GDPR Processing Activities, to the extent required by and in accordance with applicable law. In certain cases, you may also have a right, with respect to your Personal Data collected and used in the GDPR Processing Activities, to:
- correct or update any of your Personal Data that is inaccurate;
- restrict or limit the ways in which we use your Personal Data;
- object to the processing of your Personal Data;
- request the deletion of your Personal Data; and
- obtain a copy of your Personal Data in an easily accessible format.
To submit a request, please send an email message to email@example.com. Because we want to avoid taking action regarding your Personal Data at the direction of someone other than you, we will ask you for information verifying your identity. We will respond to your request within a reasonable timeframe.
Subject to certain legal limits, you also have the right to withdraw your consent to our processing of your Personal Data as part of our GDPR Processing Activities, where our processing is solely based on your consent. In some cases, you can do this by discontinuing use of the services involved in the GDPR Processing Activities. This would include by closing all of your online accounts with us and contacting us at email@example.com to request that your Personal Data be deleted. If you withdraw your consent to the use or sharing of your Personal Data for the purposes set out in these Disclosures or the other Visible Body privacy statements that link to or expressly adopt these Disclosures, you may not have access to some or all of the related services, and we might not be able to provide you some or all of the services. Please note that, in certain cases, we may continue to process your Personal Data after you have withdrawn consent and requested that we delete your Personal Data, if we have a legal basis to do so. For example, we may retain certain data if we need to do so to comply with an independent legal obligation, if we still need the data for the lawful purposes for which we obtained the data, or if it is necessary to do so to pursue our legitimate interest in keeping our services and operations safe and secure or to safeguard our rights or the rights or safety of others.
If you have any complaints regarding our privacy practices, you have the right to make a complaint with your national data protection authority (i.e., supervisory authority).
F. User Generated Content
Some of our online activities enable users to submit their own content. Please remember that any Personal Data you submit or post as user-generated content in these circumstances could in some cases be seen by others or become public. You should exercise caution when deciding to disclose your personal, financial or other information in such submissions or posts. We cannot prevent others from using that information in a manner that may violate these Disclosures, the law or your personal privacy and safety. We are not responsible for the results of such postings.
G. Updates to the Disclosures
We may update these Disclosures from time to time without prior notice by posting revised Disclosures to this site. You can determine when these Disclosures were last revised by checking the Last Updated date at the beginning of these Disclosures.
H. Contact Us
If you have any questions, comments, requests or concerns about these Disclosures or other privacy-related matters, you may contact us in the following ways:
- Email: email@example.com
- Mail: Visible Body
492 Old Connecticut Path, Suite 501
Framingham, MA 017014
Attn: Information
CCPA Privacy Notice for CA Residents
This PRIVACY NOTICE FOR CALIFORNIA RESIDENTS and applies solely to visitors, users, and others who reside in the State of California ("consumers" or "you"). We adopt this notice to comply with the California Consumer Privacy Act of 2018 ("CCPA") and other California privacy laws. Any terms defined in the CCPA have the same meaning when used in this notice.
Information We Collect
We collect information that identifies, relates to, describes, references, is capable of being associated with, or could reasonably be linked, directly or indirectly, with a particular consumer or device ("personal information"). In particular, we have collected the following categories of personal information from consumers within the last twelve (12) months:
|A. Identifiers.
|A real name, alias, postal address, unique personal identifier, online identifier, Internet Protocol address, email address, account name, Social Security number, driver's license number, passport number, or other similar identifiers.
|B. Personal information categories listed in the California Customer Records statute (Cal. Civ. Code § 1798.80(e)).
|A name, signature, Social Security number, physical characteristics or description, address, telephone number, passport number, driver's license or state identification card number, insurance policy number, education, employment, employment history, bank account number, credit card number, debit card number, or any other financial information, medical information, or health insurance information. Some personal information included in this category may overlap with other categories.
|C. Protected classification characteristics under California or federal law.
|Age (40 years or older), race, color, ancestry, national origin, citizenship, religion or creed, marital status, medical condition, physical or mental disability, sex (including gender, gender identity, gender expression, pregnancy or childbirth and related medical conditions), sexual orientation, veteran or military status, genetic information (including familial genetic information).
|D. Commercial information.
|Records of personal property, products or services purchased, obtained, or considered, or other purchasing or consuming histories or tendencies.
|E. Biometric information.
|Genetic, physiological, behavioral, and biological characteristics, or activity patterns used to extract a template or other identifier or identifying information, such as, fingerprints, faceprints, and voiceprints, iris or retina scans, keystroke, gait, or other physical patterns, and sleep, health, or exercise data.
|F. Internet or other similar network activity.
|Browsing history, search history, information on a consumer's interaction with a website, application, or advertisement.
|G. Geolocation data.
|Physical location or movements.
|H. Sensory data.
|Audio, electronic, visual, thermal, olfactory, or similar information.
|I. Professional or employment-related information.
|Current or past job history or performance evaluations.
|J. Non-public education information (per the Family Educational Rights and Privacy Act (20 U.S.C. Section 1232g, 34 C.F.R. Part 99)).
|Education records directly related to a student maintained by an educational institution or party acting on its behalf, such as grades, transcripts, class lists, student schedules, student identification codes, student financial information, or student disciplinary records.
|K. Inferences drawn from other personal information.
|Profile reflecting a person's preferences, characteristics, psychological trends, predispositions, behavior, attitudes, intelligence, abilities, and aptitudes.
Personal information does not include:
- Publicly available information from government records.
- De-identified or aggregated consumer information.
- Information excluded from the CCPA's scope, like:
- health or medical information covered by the Health Insurance Portability and Accountability Act of 1996 (HIPAA) and the California Confidentiality of Medical Information Act (CMIA) or clinical trial data;
- personal information covered by certain sector-specific privacy laws, including the Fair Credit Reporting Act (FRCA), the Gramm-Leach-Bliley Act (GLBA) or California Financial Information Privacy Act (FIPA), and the Driver's Privacy Protection Act of 1994.
We obtain the categories of personal information listed above directly and indirectly from activity on our website and in our applications. For example, from submissions through our website portal or website usage details collected automatically.
Use of Personal Information
We may use or disclose the personal information we collect for one or more of the following business purposes:
- To fulfill or meet the reason for which the information is provided. For example, if you share your name and contact information to request pricing information or ask a question about our products or services, we will use that personal information to respond to your inquiry.
- To provide you with information, products or services that you request from us.
- To provide you with email alerts, event registrations and other notices concerning our products or services, or events or news, that may be of interest to you.
- To carry out our obligations and enforce our rights arising from any contracts entered into between you and us, including for billing and collections.
- To improve our website and present its contents to you.
- For testing, research, analysis and product development.
- As necessary or appropriate to protect the rights, property or safety of us, our clients or others.
- To respond to law enforcement requests and as required by applicable law, court order, or governmental regulations.
- As described to you when collecting your personal information or as otherwise set forth in the CCPA.
- To evaluate or conduct a merger, divestiture, restructuring, reorganization, dissolution, or other sale or transfer of some or all of our assets, whether as a going concern or as part of bankruptcy, liquidation, or similar proceeding, in which personal information held by us is among the assets transferred.
We will not collect additional categories of personal information or use the personal information we collect for materially different, unrelated, or incompatible purposes without providing you notice.
Sharing Personal Information
We may disclose your personal information to a third party for a business purpose. When we disclose personal information for a business purpose, we enter a contract that describes the purpose and requires the recipient to both keep that personal information confidential and not use it for any purpose except performing the contract.
In the preceding twelve (12) months, we have disclosed the following categories of personal information for a business purpose:
Category A: Identifiers.
Category B: California Customer Records personal information categories.
We disclose your personal information for a business purpose to the following categories of third parties:
- Service providers.
- The institution you are affiliated with, if you use our products through your affiliation with an institution, such as a college or university
In the preceding twelve (12) months, we have not sold any personal information.
Your Rights and Choices
The CCPA provides consumers (California residents) with specific rights regarding their personal information. This section describes your CCPA rights and explains how to exercise those rights.
Access to Specific Information and Data Portability Rights
You have the right to request that we disclose certain information to you about our collection and use of your personal information over the past 12 months. Once we receive and confirm your verifiable consumer request, we will disclose to you:
- The categories of personal information we collected about you.
- The categories of sources for the personal information we collected about you.
- Our business or commercial purpose for collecting or selling that personal information.
- The categories of third parties with whom we share that personal information.
- The specific pieces of personal information we collected about you (also called a data portability request).
- If we disclosed your personal information for a business purpose, the personal information categories that each category of recipient obtained.
Deletion Request Rights
You have the right to request that we delete any of your personal information that we collected from you and retained, subject to certain exceptions. Once we receive and confirm your verifiable consumer request, we will delete (and direct our service providers to delete) your personal information from our records, unless an exception applies.
We may deny your deletion request if retaining the information is necessary for us or our service providers to:
- Complete the transaction for which we collected the personal information, provide a good or service that you requested, take actions reasonably anticipated within the context of our ongoing business relationship with you, or otherwise perform our contract with you.
- Detect security incidents, protect against malicious, deceptive, fraudulent, or illegal activity, or prosecute those responsible for such activities.
- Debug products to identify and repair errors that impair existing intended functionality.
- Exercise free speech, ensure the right of another consumer to exercise their free speech rights, or exercise another right provided for by law.
- Comply with the California Electronic Communications Privacy Act (Cal. Penal Code § 1546 seq.).
- Engage in public or peer-reviewed scientific, historical, or statistical research in the public interest that adheres to all other applicable ethics and privacy laws, when the information's deletion may likely render impossible or seriously impair the research's achievement, if you previously provided informed consent.
- Enable solely internal uses that are reasonably aligned with consumer expectations based on your relationship with us.
- Comply with a legal obligation.
- Make other internal and lawful uses of that information that are compatible with the context in which you provided it.
Exercising Access, Data Portability, Deletion, and Opt-out Rights
To exercise the access, portability, deletion, or opt-out rights described above, please submit a verifiable consumer request to us by email at email@example.com or by mail at:
Visible Body
492 Old Connecticut Path, Suite 501
Framingham, MA 01701
Attn: Information
Only you or a person registered with the California Secretary of State that you authorize to act on your behalf, may make a verifiable consumer request related to your personal information. You may only make a verifiable consumer request for access or data portability twice within a 12-month period. The verifiable consumer request must:
- Provide sufficient information that allows us to reasonably verify you are the person or an authorized representative of the person we collected personal information on.
- Describe your request with sufficient detail that allows us to properly understand, evaluate, and respond to it.
We cannot respond to your request or provide you with personal information if we cannot verify your identity or authority to make the request and confirm the personal information relates to you. Making a verifiable consumer request does not require you to create an account with us. We will only use personal information provided in a verifiable consumer request to verify the requestor's identity or authority to make the request.
Response Timing and Format
We endeavor to respond to a verifiable consumer request within 45 days of its receipt. If we require more time (up to 90 days), we will inform you of the reason and extension period in writing. If you have an account with us, we will deliver our written response to that account. If you do not have an account with us, we will deliver our written response by mail or electronically, at your option. Any disclosures we provide will only cover the 12-month period preceding the verifiable consumer request's receipt. The response we provide will also explain the reasons we cannot comply with a request, if applicable. For data portability requests, we will select a format to provide your personal information that is readily usable and should allow you to transmit the information from one entity to another entity without hindrance.
We do not charge a fee to process or respond to your verifiable consumer request unless it is excessive, repetitive, or manifestly unfounded. If we determine that the request warrants a fee, we will tell you why we made that decision and provide you with a cost estimate before completing your request.
We will not discriminate against you for exercising any of your CCPA rights. Unless permitted by the CCPA, we will not:
- Deny you goods or services.
- Charge you different prices or rates for goods or services, including through granting discounts or other benefits, or imposing penalties.
- Provide you a different level or quality of goods or services.
- Suggest that you may receive a different price or rate for goods or services or a different level or quality of goods or services.
Changes to Our Privacy Notice
We reserve the right to amend this privacy notice at our discretion and at any time. When we make changes to this privacy notice, we will notify you by email or through a notice on our website homepage.
Contact Information
If you have any questions or comments about this notice, our Privacy Notice, the ways in which we collect and use your personal information, your choices and rights regarding such use, or wish to exercise your rights under California law, please do not hesitate to contact us at:
Visible Body
492 Old Connecticut Path
Framingham, MA 01701
Attn: Information


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Civil War Monuments
The issue of removing American Civil War statues was violently thrust into all our lives recently. The sight of Confederate and Nazi flags being carried side by side through the streets of Charlottesville, is something that shocked many in this country, and around the world. Riots, street fighting, and the tragic loss of life have led to more protests. In Durham, a mob pulled down a statue, while in Baltimore, and other cities and towns across America, under the cover of darkness, more statues have been removed. It is difficult for some to understand why statues and monuments commemorating a war that ended 152 years ago still provoke so much passion. But for those hoping that the issue has now gone away, if the English Civil War is anything to go by, then the subject is likely to rear it's head again soon.
Outside the Houses of Parliament in London stands the statue of Oliver Cromwell. Leaning on his sword eyes looking down at the ground, the effigy of Cromwell, victor in the English Civil War (1642-46) and Lord Protector of England (1653-58), was erected in 1899. Across the street, set into the walls of St. Margaret's Church is the bust of King Charles I, Cromwell's adversary. In 1649, Charles I was tried for treason and executed in Whitehall. I once heard a myth about the statue that Cromwell looks down, ashamed of executing his king, while Charles's bodiless head defiantly glares back from across the road. The king's bust was placed on St. Margaret's in 1956, 60 years after Cromwell's statue was built. Bogus myths aside, even after all this time emotions are still raw, and strong opinions are held regarding English Civil War monuments.
After the restoration of the monarchy in 1660, King Charles II was to seek a macabre revenge. On January 31st, 1661, 12 years after the execution of his father, the King ordered that the body of Cromwell, and other leading Parliamentarians be exhumed and subjected to a posthumous execution. Hanged in chains at Tyburn (now Marble Arch), Cromwell's head was then stuck on a pole and displayed outside Westminster Hall until 1685.
In 1875, over two centuries after the Civil War, the first statue of Oliver Cromwell was erected in Manchester, outside the cathedral. As well as being highly controversial, the statue received the scorn of Queen Victoria who had agreed to open the new Town Hall building, as long as the statue was removed. It wasn't, and the town hall was opened without the presence of the Queen. When the statue of Oliver Cromwell was commissioned and placed outside Parliament in 1899, it was so controversial (especially with the Irish Nationalist Party and members of the Royal Family) it had to be built with private funds only. And even as late as 2004, some Members of Parliament proposed a motion to have Cromwell's statue taken down.
Even without the emotive subject of slavery and race that stir many Americans, the legacy of that civil war and how to commemorate it, 370 years later, can still be an issue for many people. I am sure the consequences and legacy of the American Civil War are going to be felt many centuries from now.
9/1/2017 03:30:58 pm
Great piece Andy. Trying to erase history is wrong, use it to educate and learn from!
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I don't really know anything about Richard Allen. I just saw the cover art of his record In The Front Room on Bandcamp's new arrivals and it just kind of looked like one that I might like, so I decided to hit the play button. It was a rather splendid decision, because I was hooked in a few seconds when Richard Allen started playing and beautiful, quite traditional English folk music filled the air. I bought the digital download after listening to this for a few minutes. I'm not the biggest expert on English / British folk music, but this certainly takes me back to the early 70s where people like Nick Drake, Bert Jansch, Sandy Denny and Kevin Ayers ruled the world. I'm loving this wholeheartedly at the moment. You can stream(+buy) the whole magically enchanting folk album at Bandcamp. This is Will I Ever Lean? from the album.
Staying on the same ballpark. James Frost is also an English folk musician whose new Nameless EP reflects the spirit of those 70s English folk maestros I mentioned above. I've had this on the play list for several weeks and I like it a lot. Especially this title track Nameless is just wonderful. You can again buy / stream the whole thing over at Bandcamp.


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"The End of Universal Rationality"
Yochai Benkler discusses the use of the "assumption of universal rationality and a sub-assumption that what that rationality tries to do is maximize returns to the self" as a primary analytical foundation for our models of sociological, political, and economic behavior:
The End of Universal Rationality, The Edge: The big question I ask myself is how we start to think much more methodically about human sharing, about the relationship between human interest and human morality and human society. The main moment at which I think you could see the end of an era was when Alan Greenspan testified before the House committee and said, "My predictions about self-interest were wrong. I relied for 40 years on self-interest to work its way up, and it was wrong." For those of us like me who have been working on the Internet for years, it was very clear you couldn't encounter free software and you couldn't encounter Wikipedia and you couldn't encounter all of the wealth of cultural materials that people create and exchange, and the valuable actual software that people create, without an understanding that something much more complex is happening than the dominant ideology of the last 40 years or so. But you could if you weren't looking there, because we were used in the industrial system to think in these terms.
A lot of what I was spending my time on in the 90s and the 2000s was to understand why it is that these phenomena on the Net are not ephemeral. Why they're real. But I think in the process of understanding that, I had to go back and ask, where are we really in between this what's-in-it-for-me versus the great altruists and the stories of Stahanovich and the self-sacrifice for the community?
Both of them are false. But the question is, how do we begin to build a new set of stories that will let us understand both? The stories are actually relatively easy. How we build actual, tractable analysis that allows us to convert what in some sense we all know, that some of us are selfish and some of us aren't. That actually most of us are more selfish some of the time and less selfish other of the time and in different relations. That we don't all align according to the standard economic model of selfish rationality, but that we're also not saints. Mother Teresa wouldn't be Mother Teresa if everybody were like her.
So this is the puzzle that I'm really trying to chew on now, which is how we move from knowing this intuitively and having a folk wisdom about it to something that probably won't in any immediate future have the tractability and precision of mainstream economics. Not, by the way, that as we sit here today, mainstream economics necessarily enjoys the high status that it might have a few years ago, but nonetheless so that we will be able to start building systems in the same way that we thought about building organizational systems around compensation, like options that ties the incentives of the employees to that of the business, like we thought with regard to political science that's completely pervaded today by the understanding of, how does politics happen? Well, it depends on what the median voter wants and what the median Senator wants, and all of that.
We have a lot of sophisticated analyses that try, with great precision, to predict and describe existing systems in terms of an assumption of universal rationality and a sub-assumption that what that rationality tries to do is maximize returns to the self. Yet we live in a world where that's not actually what we experience. The big question now is how we cover that distance between what we know very intuitively in our social relations, and what we can actually build with. ... [...continue reading or watch the video...]
Posted by Mark Thoma on Tuesday, March 31, 2009 at 03:33 PM in Economics, Methodology |
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Dell Medical School at The University of Texas at Austin Visual Identity
Austin, TX
Project Description
The University of Texas at Austin is the first Tier One public university in the United States to build a new medical school in almost 50 years.
The vision of the Dell Medical School is to develop new approaches for teaching, patient care, and research - all with the greater goal to transform medical education and healthcare delivery. With the intent to capture this ambitious spirit, Dyal and Partners (now Dyal Branding & Graphics, A Page Company) was charged with developing an identity for the new medical school that communicates innovation and energy and would enhance efforts to recruit faculty and students and develop groundbreaking curricula and partnerships.
Looking at everything with fresh eyes and a new start is at the heart of the mission and led to the creation of the "Rethink Everything" identity and campaign. Dyal Branding & Graphics designed various print and digital collateral pieces for the campaign, and developed extensive brand guidelines which the school has used to implement other communication pieces, including video and brochures. The campaign has become an effective tool for promoting the school and its greater vision of transforming healthcare. Community leaders have embraced the campaign as a way of talking about the medical school and its impact on the community and wellbeing of Austin.
Dell Medical School was constructed in the southeastern portion of the UT Austin campus. The school's inaugural Fall 2016 class of students were the first users of the new building. The school includes research, educational and administrative facilities, as well as a medical office building and parking garage. Page served as architect of record and design partner for all buildings on the campus.
"The Dyal and Partners team took the time to really understand our branding goals, and then visually brought the brand to life. As part of the creative process, they also proactively shaped our first brand campaign that incorporated great design, compelling messaging and flexibility."
– John Daigre, Executive Director of Communications & External Affairs, Dell Medical School | The University of Texas at Austin
Professional Services
Brand Identity
Communications Strategy
Graphic Design
Publications + News
- A District Built For Health
- Breaking Ground on a Ground-up Medical School
- Nurturing Resiliency through Relationships
- Overview: Dell Medical School at The University of Texas at Austin Updates
- Winner: Community Impact Award


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Black Doll Inc.Janet Jackson is back. Her Unbreakable World Tour begins tonight in Vancouver, Canada, supporting her forthcoming album of the same name, Janet's first since 2009. The massive, 69-show tour, which will see Janet hit North America, Hawaii and Japan, will wrap up March 9 in Ft. Lauderdale, Florida.
Although no release date has been announced for the album, it's expected this fall. Now her long time producers, Jimmy Jam & Terry Lewis, are revealing inside details about the making of the much-anticipated album.
For one thing, the pair tell Entertainment Weekly, the album and tour were conceived simultaneously. In fact, Jam says, in the final stages of working on the album, Janet would show up at the studio after working all day at rehearsals for the stage show.
The producers, who were behind Jackson's biggest hits, including "That's The Way Love Goes," "Again" and "All for You," say Unbreakable's lead single, "No Sleeep" featuring J. Cole, was something of an accident.
"'No Sleeep' was basically called that because it was like five in the morning, and we had just completed a day of work and I was still awake, so I was playing around with some different stuff and came up with the skeleton of it," Jam remembers. The track sat on his computer, half remembered until Lewis came across it and played it back. "Janet said, 'Ooh, what's that?' I told her it was a track I did like two months ago," Jam says. "Janet loved it — just the feeling that she got when she heard it is the feeling she wanted the fans to have. Just a warm, welcoming, sensual feel. But it was almost forgotten."
Jam also says the album may surprise some long-time fans. "I think it's totally different from any of her other albums," he says. "But it feels like her. At the end of the day, I go back to that. The thing about this album is there's a lot of different places that it touches, but at the end of the day, it's pure Janet."
Here are Janet's Unbreakable World Tour dates:
8/31 — Vancouver, BC, Rogers Arena
9/2 — Calgary, AB, Scotiabank Saddledome
9/4 — Edmonton, AB, Rexall Place
9/5 — Grande Prairie, Canada, Revolution Place
9/7 — Saskatoon, Canada, SaskTel Centre
9/8 — Winnipeg, MB, MTS Centre
9/11 — Grand Rapids, MI, Van Andel Arena
9/12 — Cincinnati, OH, PNC Pavilion at Riverbend
9/15 — Toronto, ON, Air Canada Centre
9/17 — Raleigh, NC, Walnut Creek Amphitheater
9/18 — Charlotte, NC, PNC Music Pavilion
9/20 — Miami, FL, American Airlines Arena
9/23 — Orlando, FL, Amway Center
9/24 — Tampa, FL, Amalie Arena
9/26 — Atlanta, GA, Chastain Park Amphitheater
9/27 — Nashville, TN, Ascend Amphitheater
9/29 — Memphis, TN, Fedex Forum
9/30 — New Orleans, LA, Smoothie King Center
10/9 — Las Vegas, NV, AXS at Planet Hollywood
10/10 — Las Vegas, NV, AXS at Planet Hollywood
10/13 — San Francisco, CA, Bill Graham Civic Auditorium
10/14 — San Francisco, CA, Bill Graham Civic Auditorium
10/16 — Los Angeles, CA, The Forum
10/17 — San Diego, CA, Viejas Arena
10/19 — Phoenix, AZ, Comerica Theatre
10/21 — Santa Barbara, CA, Santa Barbara Bowl
10/22 — Santa Barbara, CA, Santa Barbara Bowl
10/24 — Salt Lake City, UT, Energy Solutions Arena
10/25 — Denver, CO, Pepsi Center
10/27 — Kansas City, MO, Sprint Center
10/29 — St Louis, MO, Chaifetz Arena
10/30 — Omaha, NE, Centurylink Center
11/1 — Minneapolis, MN, Target Center
11/3 — Chicago, IL, Chicago Theater
11/4 — Chicago, IL, Chicago Theater
11/6 — Chicago, IL, Chicago Theater
11/12 — Honolulu, HI, Neal S. Blaisdell Center
11/13 — Honolulu, HI, Neal S. Blaisdell Center
11/15 — Honolulu, HI, Neal S. Blaisdell Center
11/19 — Osaka, Japan, INTEX Center
11/21 — Tokyo, Japan, Saitama Super Arena
11/22 — Tokyo, Japan, Saitama Super Arena
1/12 — Portland, OR, Moda Center
1/13 — Seattle, WA, KeyArena
1/15 — Sacramento, CA, Sleep Train Arena
1/16 — Anaheim, CA, Honda Center
1/19 — Tucson, AZ, Tucson Arena
1/21 — San Antonio, TX, AT&T Center
1/23 — Houston, TX, Toyota Center
1/24 — Dallas, TX, American Airlines Center
1/27 — Tulsa, OK, BOK Center
1/29 — Indianapolis, IN, Bankers Life Fieldhouse
1/30 — Lexington, KY, Rupp Arena
2/1 — Columbus, OH, Schottenstein Center
2/2 — Cleveland, OH, Quicken Loans Arena
2/5 — Detroit, MI, The Palace of Auburn Hills
2/6 — Pittsburgh, PA, CONSOL Energy Center
2/17 — Newark, NJ, Prudential Center
2/19 — Bethlehem, PA, Sands Bethlehem Events Center
2/22 — Brooklyn, NY, Barclays Center
2/24 — Philadelphia, PA, Wells Fargo Center
2/26 — Boston, MA, TD Garden
2/29 — Baltimore, MD, Royal Farms Arena
3/1 — Washington, D.C., Verizon Center
3/3 — Atlanta, GA, Philips Arena
3/4 — Winston-Salem, NC, Lawrence Joel Veterans Memorial Coliseum
3/6 — Columbia, SC, Colonial Life Arena
3/8 — Jacksonville, FL, Jacksonville Veterans Memorial Arena
3/9 — Fort Lauderdale, FL, BB&T Center
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