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TiVo® Alert Larry King Live – Autism Show
Larry King Live this week (Thursday, February 14th) is featuring a show on Autism. Should be interesting with several well known parents of autistic children appearing. I'm most interested in seeing Jason McElwain though.
For those of you who don't know about Jason, let me catch you up. Jason is a child who was diagnosed as autistic as a toddler. He is considered high functioning. In high school at Greece Athena outside of Rochester, NY, Jason served as a manager of the high school basketball team for 3 years. Wanting to repay his loyalty the team coach had him suit up for the last game. Not guaranteeing Jason the chance to play, the coach did put him in for the last 4 minutes of the game. On his first opportunity to take a shot Jason did – and missed. On successive chances however Jason not only scored but scored BIG. Jason hit six 3-point shots and scored a total of 20 points tying a school record.
The bigger story here however has nothing to do with Jason and yet everything to do with Jason. The bigger story is the reception that Jason got just in entering the game. The crowd went wild. With each successive score the crowd went more crazy. (Keep in mind that the team was already well ahead at the time the coach put Jason into the game) With the finish of the game the crowd at the game rushed the floor putting Jason upon its shoulders and carrying him around the gym in triumph. (See the video at YouTube by clicking here – make sure you have a couple of hankies available)
Jason from this vantage point at least seems to be the poster child for successful inclusion/mainstreaming. While I certainly credit Jason to a great degree, one can not forget that along with Jason's apparently infectious spirit goes credit to his parents who fostered this child's attitude of staying focused and belief in self as well as a school and community who looked past a label and accepted a person.
If all our children could be so lucky as to have such love an acceptance in a mainstream setting. I wish they were available to more children, more easily, more readily, more consistently. I wish I didn't have to wish for it.
I look forward to seeing what's up with Jason now!
The description from the Larry King Live website of this Thursday's show:
The heartbreak …and hope of autism. Jason "J-Mac" McElwain inspired the world with his incredible shot-making at a high school basketball game. Larry talks to the teen and others about the disorder. Holly Robinson Peete, Doug Flutie and Toni Braxton join the discussion to bust myths and present breakthroughs. It's an uplifting hour with those who know!
Larry King Live is a nightly show on CNN which airs 9pm ET and 6pm PT.
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How to Build a High Converting Marketing Funnel [Infographic]
Want to maximize the growth potential of your business? Here's a 7 step formula you can use to consistently attract and convert more customers by building an automated marketing funnel. Infographic courtesy of Eliv8.
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Historic Rotherhithe
Rotherhithe is an 'urban village' in South East London. The name is Saxon, meaning 'Mariners' landing place', which demonstrates the long history of habitation in the area. The river Thames half surrounds the district, which used to consist of marshes, meadows, and rivulets - prehistoric animal and human remains have been found and ancient causeways, deep under the present surface of the ground, leading towards the river, give a clue about the importance of the river Thames and of the community living on its banks.
Over the centuries, the area has been transformed from one of total rurality to become one of complete urban living. There have been immeasurable changes in the social and working structures of the community - emerging from a village of mariners, ship repairers, ship breakers, whalers, market gardeners and finally, dockers.
The Docks
Docks had existed in the neighbourhood from the 17th Century, reaching a peak of activity prior to the 2nd World War. It was an area vibrant with life, highly populated, with sons following their fathers into the same trade. Even so, here was an area of great poverty and social deprivation. In the 1930's this led to Bermondsey Borough Council developing an ambitious programme of 'slum clearance' and the start of successful rebuilding.
The 2nd World War left the area severely bombed, with many human casualties. After the war, the docks required business, but the political balance of the country at this time weighed heavily against inner city trade and industry. The result of containerisation and the building of larger ships created trade further down the river at Tilbury. As a consequence the 'Surrey docks' at Rotherhithe were closed in 1971 and fell into decay. They remained derelict until the early 1980's, when the then Conservative Government led by Margaret Thatcher created the 'London Docklands Development Corporation' This had sweeping powers, was a planning authority in its own right and for a period of approximately 16 years carried out a huge programme of regeneration for London's Dockland areas.
Much good has come of this, but many problems remain; what cannot be constructed is the sense of belonging, with that closeness and concern for neighbours which underpinned the old community. Some of this remains, but much has yet to be conceived and born out of patient work and unselfish community building. Time will tell!
An Engineering Triumph
In 1825 a foot tunnel under the Thames was begun by Marc Brunel. This pioneering feat of engineering was successfully completed in 1843 by his son Isambard Kingdom Brunel. Originally it was provided with shops, but 1869 it was converted into a tunnel for use by one of the Railway Companies of Victorian England.It is still in use by London Underground. An old print of work in progress shows St Mary's in the background.
Shipping in the Pool of London, with St. Mary's in the background~
The Diving Bell at work over the Thames Tunnel;
- looking to the South Bank and St. Mary's
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The Defence Science Institute is a proud collaborator with AMSI Intern in providing research higher degree students the ability to apply their knowledge and solve real defence-related industry problems. The value of this program is not to be underestimated, increasing the size of the Defence industry ecosystem will ultimately lead to stronger innovation in this industrial sector.
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U.S. WWII Draft Cards Young Men, 1940-1947
Father: Joseph Thomas PONCE b: 15 MAR 1876 in Jacksonville, Duval County, Florida
Mother: Ethel Sarah GREEN b: 22 OCT 1879 in Duxbury, Plymouth County, Massachusetts
Marriage 1 Gertrude C. "Trudie" TODD b: 25 DEC 1910 in possibly Okaloosa County, Florida
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In rabbit proximal tubules, a basolateral ATP- and taurine-sensitive K+ channel (KATP) was shown to be involved in the regulation of the basolateral K+ conductance as a function of the rate of apical Na+ entry. To establish the molecular identity of this channel, we used degenerated primers to look for cDNA transcripts for an inwardly rectifying K+ channel (Kir6.1 and Kir6.2) and sulfonylurea receptors (SUR1, SUR2A, and SUR2B) in a cDNA library obtained from rabbit proximal tubules. PCR products were found only for Kir6.1, SUR2A, and SUR2B. Expression of Kir6.1 in Xenopusoocytes generated an additional K+ current that was found to be sensitive to external barium and intracellular taurine and to changes in intracellular ATP concentrations. To study the specificity of the taurine sensitivity, intracellular taurine was tested on several members of the Kir family expressed in Xenopus oocytes. K+ currents induced by Kir1.1A, Kir2.1, Kir3.2, Kir4.1, or Kir5.1 were insensitive to taurine, but all tested combinations of Kir6.x with or without the SUR subunit were significantly inhibited by taurine. This study suggests that the taurine-sensitive KATP channel of rabbit proximal tubules is formed by a combination of Kir6.1 plus SUR2A and/or SUR2B.
- kidney
- inwardly rectifying potassium channel
- sulfonylurea receptor
- taurine
in the kidney, the greatest part of volume reabsorption is performed by the proximal convoluted tubule (PCT), which generates an intense transepithelial NaCl transport. As this transepithelial ionic flux may vary as a function of the availability of Na+-cotransported substrates in the lumen, regulatory mechanisms exist to minimize potentially dangerous changes in cell volume and ionic composition. It was previously shown that the basolateral K+ conductance is adjusted as a function of transepithelial Na+ transport (26) and that an ATP-sensitive K+ channel is responsible for this regulation (7, 17, 31, 43). Pump-dependent changes in local ATP concentration were suggested to constitute the likely mediator of this regulatory mechanism (8,38), but other mediators could also be involved. For example, the KATP channel of the rabbit PCT was recently demonstrated to be taurine sensitive (31). As intracellular taurine has been implicated in volume regulation as an exportable osmolyte, it is a very interesting candidate for the regulation of the coupling between the basolateral K+conductance and the transepithelial Na+ transport that is known to affect cell volume (27).
Taurine sensitivity of K+ channels is a relatively new finding that has been thus far observed for KATP channels in ventricular myocytes (16, 37), proximal tubules (31), Xenopus oocytes (10), and skeletal muscle (42). However, it had not been established whether taurine sensitivity is a specific property of KATPchannels or could be extended to other members of the inwardly rectifying K+ channel family.
Originally discovered in cardiac muscle (29), KATP channels have been subsequently identified in a variety of tissues. Since 1995 it has been recognized that KATP channels are heteromultimeric proteins formed from the combination of two types of proteins: pore-forming subunits (i.e., the inwardly rectifying K+ channel, Kir 6.1 or Kir 6.2) and sulfonylurea receptors (SUR1, SUR2A, or SUR2B) (1, 19,20, 23, 36). More recently, the combination of Kir1.1A and the cystic fibrosis transmembrane conductance regulator (CFTR, like SUR, a member of the ATP-binding cassette protein family) was also shown to produce a KATP channel activity (35). A preliminary report describes a ubiquitously expressed KATP channel (uKATP-1 or Kir6.1 cloned from rat pancreatic islets; see Ref. 22) that was localized at the basolateral membrane of rat proximal tubule (5). This subunit has been subsequently cloned in human lungs (21) and mouse brains (45). However, it is still unknown whether the Kir6.1 subunit, which develops a channel with a 70-pS conductance in Xenopus oocytes (22), is the one responsible for the 50-pS channel in rabbit PCT. Attempts to determine the nature of the SUR subunits in mice and rats show that SUR1 and SUR2A mRNAs are generally absent in the kidney (9, 19, 23). On the other hand, SUR2B mRNAs are expressed in kidney as well as in all other tissues examined (heart, eye, urinary bladder, skeletal muscle, brain, lung, liver, pancreas, spleen, stomach, small intestine, colon, uterus, ovary, and fat tissue) (23). In kidney, high staining was found with SUR2B antisera in distal nephron segments, whereas low, diffuse staining was found in proximal tubules (9).
KATP channels in native tissues yield a wide variety of characteristics (such as conductance and/or sensitivity to ATP or sulfonylurea), and it is not clear whether the two Kir6.x and three SUR subunits already identified could account for such a wide variety of native KATP channels. In the kidney in general and in PCT in particular, the molecular identity and precise composition of the KATP channel remain unsettled.
As a first step in the molecular identification of the different subunits that compose the basolateral PCT KATP channel, we searched for the presence of transcripts that correspond to the most likely composition (Kir6.x plus SURx). We then expressed the corresponding proteins in Xenopus oocytes to compare important functional characteristics with what is currently known from rabbit PCT. Finally, to define whether taurine sensitivity is a specific characteristic of the KATP channel, the effect of taurine was tested on several members of the Kir family after expression in oocytes.
Molecular Biology
A suspension of cortical renal tubules from New Zealand White rabbits was prepared as described previously (24). The tubule fragments were separated in a Percoll gradient using the method of Vinay et al. (44). The F4 layer, 98% of which represents proximal tubules, was then removed from the Percoll gradient and washed three times by centrifugation. Total RNA was extracted from the PCT suspension using TRIzol reagent (Life Technologies) according to the manufacturer's instructions. Double-stranded cDNA was obtained using the Smart PCR cDNA synthesis kit (Clontech, Palo Alto, CA), which presents the advantage of a significant enrichment in full-length cDNAs.
Cloning of rabbit PCT Kir6.x.
Two degenerated PCR primers corresponding to the first 28 nucleotides (the 5′ end) and the last 22 nucleotides (the 3′ end) of human, mouse, and rat Kir6.1 (respectively, 5′-GATGYTGGCCAGRAAGAGYATCACCCGGA-3′ and 5′-TCYTGCYSTCATGATTCYGATG-3′) were used to amplify a 1,286-bp product from PCT cDNA corresponding to the full-length rabbit renal Kir6.1. The PCR product was then ligated into the pGEMT-Easy vector (Promega, Madison, WI).
Two primers directly designed from the 5′ and 3′ ends (respectively, 5′-GGCATGCTGTCCCGAAAGGGG-3′ and 5′-TCAGGACAAGGAATCTGGAGAGATGC-3′) of the cloned rabbit heart Kir6.2 (GenBank accession no. AF006262) were used in our attempt to isolate the renal Kir6.2 from the PCT cDNA.
Cloning of rabbit PCT SURx.
Four degenerated PCR primers corresponding to the 5′ end (5′-CATGCCYYTGGCCTTCTGCGG-3′ or 5′-CATGCCYYTGGCCTTCTGCGGYASC-3′) and the 3′ end (5′-TCAYTTGTCYGCRCGGAC-3′ or 5′-TCAYTTGTCYGCRCGGACRAAGG-3′) of human, rat, and hamster SUR1 were used to isolate the rabbit renal SUR1 from the PCT cDNA.
Two degenerated PCR primers corresponding to the 5′ and 3′ ends (respectively, 5′-ATGAGCCTTTCHTTYTGTGG-3′ and 5′-TCACATGTCTGCRCGRAC-3′) of rat, mouse, and human SUR2B were used to amplify a 4.8-kb product. It could correspond to the full-length rabbit renal SUR2A or SUR2B, taking into account that the 5′ ends of SUR2A and SUR2B are identical and that the selected sequence of the PCR primer corresponding to the 3′ end of SUR2B is also present in the 3′ untranslated region of SUR2A. In fact, the nucleotide sequences of SUR2A and SUR2B cloned in other species are identical apart from an insertion in the 3′ end of the coding region for SUR2A, which generates a C-terminus different from SUR2B. The 4.8-kb PCR product was purified with GFX PCR DNA and the Gel Band purification kit (Amersham Pharmacia Biotech Life Science, Cleveland, OH) and ligated into pGEMT-Easy vector. The ligated product was used to transform competent X1–2 Blue E. colibacteria (Stratagene, La Jolla, CA), which were plated onto petri dishes. Plasmids of five different colonies were purified. To determine which colony corresponded to SUR2A or SUR2B, a new pair of PCR primers was designed to frame the 3′ insert region of SUR2A and therefore amplify products of different sizes from either SUR2A or SUR2B. It was expected that the 5′ and 3′ PCR primer pair (respectively, 5′-CCG TGG TCA CCA TAG CTC-3′ and 5′-TCA CAT GTC TGC ACG AAC-3′) would amplify a 336-bp product for SUR2A and a 162-bp product for SUR2B.
The nucleotide sequence of the isolated clones was determined by a commercial sequencing service (BioS&T, Lachine, PQ) and confirmed twice. For expression in oocytes, 10 μg of pGEMT-Easy vector that contained the full-length cDNA encoding Kir6.1, SUR2A, or SUR2B were linearized with NdeI (for Kir6.1) or SpeI (for SUR2A or SUR2B) and transcribed in vitro using the mMESSAGE mMACHINE T7 Transcription Kit (Ambion, Austin, TX). Each transcript (12–30 ng) was injected into the oocytes.
Kir clones.
pSPORT (10 μg) containing cDNA that encodes rat Kir1.1A (or ROMK1, GenBank accession no. AF081365; a gift of Dr. S. J. White), was linearized with NotI and transcribed in vitro using the mMESSAGE mMACHINE T7 transcription kit. RNA (5 ng) was injected into the oocytes.
Human Kir 2.1 cDNA (1 ng; hIRK; given by Dr. R. Sauvé) and rGFP (1 ng; in pMT21 vectors) were injected intranuclearly.
Human Kir3.2 (or pBlue-HGIRK2, GenBank accession no. U52153) and human Kir4.1 (or pBlue-HGIRK15–2, GenBank accession no. HSU52155, gifts of Dr. H. Van Tol) were linearized with BamHI. Each clone was transcribed with the mMESSAGE mMACHINE T7 transcription kit, and each transcript (16 ng) was injected into the oocytes.
Rat Kir5.1 (or BIR9, GenBank accession no. AF249676; provided by Dr. Larry Salkoff) was linearized with MluI and transcribed in vitro with the mMESSAGE mMACHINE SP6 transcription kit (Ambion). RNA (16 ng) was injected into the oocytes.
Four different clones were given to us by Dr. Seino: rat Kir6.1 (linearized with HindIII), mouse Kir6.2 (linearized withXbaI), rat SUR1 (linearized with XbaI), and human SUR2A (linearized with ClaI). Each linearized clone was transcribed in vitro with the mMESSAGE mMACHINE T7 transcription kit. Oocytes were injected with 12.5 ng of each transcribed RNA.
Oocyte Preparation and Injection
Stage V and VI oocytes were removed from Xenopus laevisfrogs anesthetized with 3-aminobenzoic acid ethyl ester and were placed into Barth's solution [(in mM) 88 NaCl, 3 KCl, 0.82 MgSO4, 0.41 CaCl2, 0.33 Ca(NO3)2, and 5 HEPES; pH 7.60]. The follicular layer was removed by incubation in a Ca2+-free Barth's solution containing 1.6 mg/ml collagenase (Sigma, St. Louis, MO) as previously described (11). Defoliculated oocytes were stored at 18°C in Barth's solution supplemented with 5% horse serum, 2.5 mM sodium pyruvate, 100 U/ml penicillin, and 0.1 mg/ml streptomycin for 48 h. Healthy oocytes were then selected and injected either into the cytoplasm with 46 nl of water (±mRNA) or into the nucleus with 4.6 nl of water containing recombinant expression vector coding for green fluorescent protein with or without recombinant pMT21 vector containing the cDNA insert. The oocytes were incubated in antibiotic Barth's solution for 3–8 days before the experiments.
Two-Microelectrode Voltage-Clamp Technique
Oocyte currents were measured with the two-microelectrode voltage-clamp technique using a commercial amplifier (oocyte clamp model OC-725, Warner Instrument, Hamden, CT) as described previously (12). Current-voltage curves were obtained from 11 pulses (500-ms duration) separated by 600-ms periods at the resting potential of −40 mV. The voltage range covered was from −165 to +85 mV. Three different bath solutions were used: 1) a modified Barth's solution (M-Barth) that contained (in mM) 40 NaCl, 3 KCl, 50 n-methyl-d-glucamine-Cl (NMDG-Cl), 0.82 MgCl2, 0.74 CaCl2, and 5 HEPES/Tris, at pH 7.60; 2) a K+-enriched Barth's solution (K-Barth) that contained (in mM) 40 NaCl, 20 KCl, 33 NMDG-Cl, 0.82 MgCl2, 0.74 CaCl2, and 5 HEPES/Tris, at pH 7.60; and 3) a high-K+ Barth's solution (HK-Barth) that contained (in mM) 93 KCl, 0.82 MgCl2, 0.74 CaCl2, and 5 HEPES/Tris, at pH 7.60. Current and voltage traces were analyzed by averaging the signals in a window of 25 ms positioned after the decay of all capacitative transients.
Statistical analysis was performed using paired or unpairedt-tests as appropriate. Average values are given as means ±SE, and n represents the number of oocytes that were obtained from at least three different animals.
Cloning of Rabbit PCT Kir6.1
As there has been no reported sequence for a Kir6.x of renal origin, we first looked for the presence of transcripts corresponding to the known Kir6.x subunits, i.e., Kir6.1 or Kir6.2, in rabbit proximal tubule cDNA. Degenerated primers designed from sequences of Kir6.1 cloned in human lung, mouse brain, and rat pancreatic cells were used to amplify a 1,286-bp product (Fig.1 A). This clone, which corresponds to the full-length renal rabbit Kir6.1 (GenBank accession no. AF417509), was totally sequenced; it was predicted to code for a 424-amino-acid polypeptide where alignment through GenBank scored 95–97% identity with rat, mouse, and human Kir6.1 (Fig.1 B) and 62% identity with the rabbit Kir6.2 previously cloned from heart. As shown in Fig. 1 A, a second PCR product of lower molecular weight was also found to be amplified by the same primers but was not further studied. When primers designed from the rabbit cardiac Kir6.2 were used, no signal could be detected by PCR from our rabbit PCT cDNA (Fig. 1 A).
Cloning of Rabbit PCT SUR2A and SUR2B
A similar homology strategy was used to isolate the SUR subunits from our PCT cDNA. No product could be detected with two different pairs of degenerate PCR primers corresponding to human, rat, or hamster SUR1 (Fig. 2 A). On the other hand, two degenerated PCR primers corresponding to the 5′ and 3′ ends of mouse, rat, and human SUR2B were effective in amplifying a PCR product (Fig. 2 B) that corresponded to the size expected (about 4.8 kb) for the full-length renal rabbit SUR2A or SUR2B. A new pair of PCR primers designed to frame the 3′ end insert region of SUR2A was used to amplify (from plasmids isolated from colonies of bacteria transformed with the previously obtained 4.8-kb product) new PCR products of different size from either SUR2A and SUR2B. Among the five different plasmids isolated from five colonies of bacteria, one (no. 2 clone) yielded a 336-bp product (the expected size of a SUR2A fragment) and the four others (nos. 1, 3, 4, and 5 clones) yielded a 162-bp product (the expected size of a SUR2B fragment; Fig. 2 C; for details, see materials and methods). The no. 2 clone was predicted to code for a full-length 1,549-amino acid protein that was 100% identical to the rabbit cardiac SUR2A (GenBank accession no.AF417510), and the no. 1 clone was predicted to correspond to its splice variant SUR2B (GenBank accession no. AF417511). As expected, sequences of SUR2A and SUR2B only differ in the 3′ end, which is represented in Fig. 2 D. Alignment through GenBank has shown that the rabbit SUR2B from PCT was 96–98% identical to the rat, mouse, and human SUR2B, including the rat kidney SUR2B homologue (41).
Expression of Rabbit Kir6.1 in Xenopus Oocytes
To characterize the properties of the cloned rabbit Kir6.1 and to compare these properties with the known characteristics of the native PCT KATP channel, we first expressed Kir6.1 RNA in the absence of an exogenous SUR subunit into Xenopus laevisoocytes. We compared whole-cell currents of control oocytes with Kir6.1-injected oocytes (at 5–8 days after injection). Control oocytes developed a current of 166 ± 11 nA at +85 mV and −71 ± 13 nA at −110 mV in M-Barth (n = 7; Fig.3). Conductance was higher in Kir6.1-injected oocytes: 441 ± 39 nA at +85mV and −192 ± 23 nA at −110 mV in M-Barth (n = 23). When oocytes expressed Kir6.1 RNA, the reversal potential measured in control conditions (M-Barth) was slightly depolarized (−31 ± 1 mV) compared with control oocytes (−40 ± 5 mV). In Kir6.1-expressing oocytes, as extracellular K+ was increased (from 3 mM in M-Barth to 20 mM in K-Barth and 93 mM in HK-Barth), the reversal potentials shifted to more-positive values (−31 ± 1 mV in M-Barth, −21 ± 2 mV in K-Barth, and −3 ± 0.5 mV in HK-Barth; see Fig. 3). These values indicate a partial selectivity of the whole-cell current for K+ (the partial conductance of potassium, GK/Gtot= 0.2 and 0.5 when calculated from the reversal potential, respectively, in M-Barth vs. K-Barth and K-Barth vs. HK-Barth). This estimation is probably an underevaluation of true selectivity considering that changes in local intracellular K+ concentration will follow changes in external K+ concentration and affect the selectivity calculation. In addition, inward currents activated by external addition of K+ (90 mM K+ increase from M-Barth to HK-Barth) were significantly higher in Kir6.1-expressing oocytes (285 ± 20 nA at −110 mV; n = 23;P < 0.001; see Fig. 3) than in control oocytes (101 ± 9 nA at −110 mV; n = 7; see Fig. 3).
To confirm the presence of a K+ current, the inhibitory effect of barium was tested. In the presence of 5 mM external barium, the currents of Kir6.1-expressing oocytes decreased to a level close to control currents (Fig. 4 A). External barium inhibited the currents in both directions (barium-sensitive currents of 154 ± 18 nA and −108 ± 17 nA at +85 and −110 mV; n = 7). The reversal potential of the Ba2+-sensitive current was found to be −22 ± 4 mV in K-Barth, which is consistent with an intracellular K+concentration of ∼48 mM.
As Kir6.1 is a KATP channel, we characterized its ATP sensitivity. A 10-min treatment with 3 mM sodium azide, which has been shown to decrease the oocyte ATP level from 2.3 to 1.7 mM on average (14), had no effect on control oocytes (see Fig.4 B, inset). In contrast, in Kir6.1-expressing oocytes, sodium azide increased the currents (from 560 ± 120 nA to 930 ± 230 nA at +85 mV and from −180 ± 78 nA to −340 ± 82 nA at −110 mV), and a significant sodium azide current was measured (375 ± 140 nA; P < 0.05, and 160 ± 35 nA; P < 0.025, respectively, at +85 and −110 mV; n = 4; see Fig. 4 B). The reversal potential of the current induced by the sodium azide treatment was found to be −22 ± 1 mV in K-Barth.
Finally, as the KATP channel of the PCT was shown to be taurine sensitive, we tested the sensitivity to taurine of the Kir6.1 clone. Taurine sensitivity was tested by comparing the effect of injecting taurine versus mannitol in two sets of Kir6.1-expressing oocytes. More precisely, the current-voltage curves of a given number of oocytes were measured just before they were injected with either mannitol or taurine (final intracellular concentration reached ∼40 mM). After a period of 1–2 h to allow for recovery toward the resting oocyte resistance, the total current-voltage curve was determined for each oocyte a second time. Although mannitol injection produced an increase in the current measured at both +85 and −110 mV (150 ± 49 nA at +85 mV; P < 0.025, and 59 ± 66 nA at −110 mV; not significant; n = 8), taurine produced a significant decrease at the same potentials (135 ± 36 nA; P < 0.025, and 150 ± 43 nA;P < 0.010, respectively, measured at +85 mV and at −110 mV after taurine injection; n = 8). This is illustrated for the current measured at +85 mV in Fig.5 A. Taurine-sensitive currents were determined by subtraction with each Kir6.1-expressing oocyte serving as its own control (Fig. 5 B). The reversal potential of this current was −23 ± 2 mV.
Expression of Kir6.1 and SUR2A or SUR2B in Xenopus Oocytes
To compare the properties of the native PCT KATPchannel with those of cloned rabbit subunits, we expressed Kir6.1 RNA combined with SUR2A or SUR2B RNA. Expression in oocytes of Kir6.1 combined with SUR2A or SUR2B induced similar K+ currents (see Fig. 6 A: for SUR2A in K-Barth, the current measured 650 ± 110 nA at +85 mV and −220 ± 33 nA at −110 mV with a reversal potential of −30 ± 4 mV; n = 4; and for SUR2B in K-Barth, it was 1,470 ± 515 nA at +85 mV and −250 ± 75 nA at −110 mV with a reversal potential of −28 ± 8 mV; n = 4).
As the SUR subunits are responsible for the glibenclamide sensitivity, we tested the effect of increasing the concentration of glibenclamide (from 1 to 100 μM) on oocytes expressing Kir6.1/SUR2A. In four oocytes injected with a combination of Kir6.1/SUR2A, with respect to four control oocytes of the same batches, a specific current of 460 ± 120 nA at +85 mV could be measured. Application of 1-, 10-, 50-, and 100-μM glibenclamide produced a rapid inhibition (within 1 min) by 8, 32, 49, and 57%, respectively (P < 0.05 in all cases; see Fig. 6 B). Currents of Kir6.1/SUR2B-expressing oocytes were also inhibited by a 100-μM concentration of glibenclamide (74 ± 9% inhibition at +85 mV; n = 3). In contrast, glibenclamide had no measurable effect on oocytes expressing Kir6.1 alone (1 ± 3% inhibition at +85 mV using 100 μM glibenclamide; n = 3).
Taurine Sensitivity of Several Kir Family Members
Effect of taurine on ROMK1 channels.
The ATP-dependent rat Kir1.1A (ROMK1) RNA expressed in oocytes developed large currents (−13,000 ± 3,700 nA at −110 mV;n = 10) compared with that measured in control oocytes (−283 ± 67 nA at −110 mV in K-Barth; n = 3). A weak inward rectification was observed. Taurine sensitivity of the ROMK1 clone was then tested as previously described comparing the effect of intracellular mannitol versus taurine. Mannitol injection produced a weak decrease of the whole-cell currents at both +60 mV and −110 mV, which turned out to be statistically nonsignificant (−36 ± 19% and −20 ± 31%, respectively, at +60 mV and −110 mV; nonsignificant; n = 5). Similarly, taurine injection did not significantly modify whole-cell currents at either +60 mV or at −110 mV (−28 ± 24% and −12 ± 26%, respectively, at +60 mV and −110 mV; nonsignificant; n= 5; Table 1).
Effect of taurine on Kir2.1 channels.
Kir2.1 (IRK1) cDNA expression developed large inwardly rectifying currents (−17,000 nA at −80 mV; n = 7) in the presence of 20 mM K+ in the bath solution. Clearly, taurine injection failed to produce an inhibitory effect at all tested potentials (65 ± 53% and 12 ± 33% increases, respectively, at +60 mV and −80 mV; n = 7; Table 1).
Effect of taurine on Kir3.2 channels.
Human Kir3.2 RNA expression produced a modest but significant increase in whole-cell currents compared with control oocytes (−333 ± 63 nA and −77 ± 21 nA, respectively, for Kir3.2-expressing oocytes and control oocytes at −110 mV in K-Barth; n = 3). Unlike Kir2.1, which is a strongly inwardly rectifying K+channel, Kir3.2-expressing oocytes developed currents with an apparent outward rectification in the presence of 20 mM external K+. Either mannitol or taurine produced a slight nonsignificant decrease of membrane currents (−35 ± 23% and −16 ± 43%, respectively, at +85 mV and −110 mV after mannitol injection; and −10 ± 23% and −4 ± 53%, respectively, at +85 mV and −110 mV after taurine injection; n = 8; see Table 1).
Effect of taurine on Kir4.1 channels.
Expression of the human Kir4.1 ATP-dependent K+ channel in oocytes developed an apparent outwardly rectifying K+current in the presence of 20 mM external K+ (411 ± 34 nA and −214 ± 17 nA, respectively, at +85 mV and −110 mV in K-Barth; n = 13). In the same batch of oocytes, control currents of 130 ± 15 nA at +85 mV and −102 ± 16 nA at −110 mV were measured (n = 9). Although mannitol injection produced a weak decrease in membrane currents (−29 ± 12% and −35 ± 16%, respectively, at +85 mV and −110 mV), membrane currents measured before and after taurine injection were similar (+15 ± 26% at +85 mV and −22 ± 18% at −110 mV after taurine injection; see Table 1).
Effect of taurine on Kir5.1 channels.
Kir5.1 expression produced a two-to-threefold increase in whole-cell currents compared with control oocytes (−278 ± 61 nA and −115 ± 4 nA, respectively, for Kir5.1-expressing oocytes and control oocytes at −110 mV in K-Barth; n = 10). In rat Kir 5.1 RNA-expressing oocytes, membrane currents measured in K-Barth before mannitol injection were not significantly different from those measured after mannitol injection (−22 ± 30% at +85 mV and +5 ± 52% at −110 mV; not significant). The same observation was made with taurine injection (−25 ± 19% at +85 mV and −17 ± 43% at −110 mV; not significant; see Table 1).
Effect of taurine on different combinations of Kir6.x and SUR subunits.
As shown in Fig. 5, the cloned rabbit proximal Kir 6.1 expressed in oocytes developed taurine-sensitive K+ channels. To determine whether taurine sensitivity is a specific property of KATP channels, the effects of taurine were tested on different combinations of Kir and SUR subunits (Kir6.1, Kir6.2, SUR1, and SUR2A) cloned in different species.
In oocytes expressing rat Kir6.1 plus rat SUR1 (whole-cell current of −1,300 ± 300 nA at −110 mV in K-Barth), mannitol injection induced a slight increase in membrane currents (+14 ± 24% at +60 mV and +51 ± 42% at −110 mV, not significant; n= 8), whereas taurine significantly inhibited membrane currents at all tested membrane potentials (−46 ± 16% at +60 mV;P < 0.005, and −39 ± 16% at −110 mV;P < 0.05; n = 10; see Table 1).
Rat Kir6.1 was also expressed with human SUR2A (whole-cell current of −518 ± 68 nA at −110 mV in K-Barth; n = 14), and the effects of both mannitol and taurine were tested. It was observed that taurine significantly reduced the membrane currents at all tested potentials (−37 ± 14% at +85 mV, P< 0.05, and −40 ± 15% at −110 mV, P < 0.05;n = 6; see Table 1). In comparison, mannitol had no significant effect at all tested potentials (−31 ± 26% at +85 mV and +14 ± 67% at −110 mV).
The effect of taurine was also tested on the Kir6.2 subunit coexpressed with SUR1 (whole-cell current of −570 ± 83 nA at −110 mV in K-Barth; n = 24) and SUR2A (whole-cell current of 830 ± 174 nA at −110 mV in K-Barth; n = 24). It was observed that membrane currents in taurine-injected Kir6.2/SUR1-expressing oocytes were smaller (−30 ± 14% at +85 mV, P < 0.05, and −38 ± 13% at −110 mV,P < 0.01; n = 24; see Table 1) than membrane currents in mannitol-injected Kir6.2/SUR1-expressing oocytes. In Kir6.2/SUR2A-expressing oocytes, taurine significantly reduced the membrane currents (−24 ± 11% at +85 mV, P < 0.05, and −58 ± 18% at −110 mV; P < 0.005; Table 1). Mannitol had no significant effect (−16 ± 26% at +85 mV and +3 ± 40% at −110 mV, not significant; n= 24).
Taurine-sensitive inward currents expressed as a percentage of the measured inward current before taurine injection are systematically correlated with the known ATP sensitivity on all tested Kir members in Table 1. If we pool all the experiments with the different combinations involving Kir6.1, taurine produced an inhibition of 40% of the inward current measured at −110 mV, whereas the effect of taurine on Kir6.2 averaged 47%. The two effects are not significantly different. This inhibition is an underestimation, because injection of mannitol produces an average increase of 27%.
The goal of this study was to determine the molecular identity of the KATP channel of the rabbit PCT and to define some of the regulatory properties of the cloned channels. A homology cloning strategy was used to isolate from our PCT cDNA the Kir6.1, SUR2A, and SUR2B subunits. Expressed in Xenopus oocytes, Kir6.1 by itself forms a functional K+ channel, and the induced K+ current was shown to be sensitive to extracellular K+, external barium, cytosolic ATP levels, and intracellular taurine. Expression of Kir6.1 combined with SUR2A or SUR2B generates a glibenclamide-sensitive K+ current. These properties, including the specific inhibitory effect of taurine, are also found for the native PCT KATP channel.
Molecular Identity of the Rabbit PCT KATP Channel
A wide variety of KATP channels have been directly observed in different epithelial and nonepithelial cells. The conductances range from 9 to 300 pS and the sensitivities to ATP and glibenclamide vary considerably: the IC50 ranges from 10 μM to 1 mM for ATP and from 3 nM to 250 μM for glibenclamide (30, 33, 38). At the molecular level, reconstitution of ATP-sensitive K+ channels with cloned Kir6.x and SURx subunits suggests that Kir6.2/SUR1 could represent the pancreatic β-cell KATP channel, Kir6.2/SUR2A or Kir6.2/SUR2B could be responsible, respectively, for the cardiac and smooth muscle KATP channels, and Kir6.1/SUR2B could account for the vascular smooth muscle KATP type (for review, see Ref.39). However, other combinations could be required to explain the functional characteristics of all KATP channels previously identified. For example, it was recently shown (13) that Kir6.1 and Kir6.2 can coassemble to produce functional channels. In addition, other subunits could be implicated, as it was shown that a combination of Kir1.1 (ROMK1) with CFTR could produce a bona fide KATP channel (35).
In the case of PCT and other renal segments, the composition of the observed KATP channels is not clear. In a preliminary report (5), the ubiquitously expressed Kir6.1 subunit was localized at the basolateral membrane of rat proximal tubule, but it is unclear whether the Kir6.1 subunit, which develops a channel with a 70-pS conductance in Xenopus oocytes (22), could be responsible for the 50-pS activity found in rabbit PCT. In addition, it seems that SUR1 and SUR2A mRNAs were absent in mouse and rat kidney (19, 23), although SUR2B mRNA was shown to be abundantly expressed in rat proximal tubule, cortical thick ascending limb (CTAL), and outer medullary collecting duct (OMCD) (41). Interestingly, the combination of mouse Kir6.1/SUR2B has been described as the vascular smooth muscle KATP type, with functional characteristics quite different from those observed in PCT cells (45). In summary, the molecular identity and the precise composition of the KATP channel in rabbit PCT is in need of clarification.
Evidence for the presence of Kir6.1 in PCT.
Our homology cloning strategy allowed us to isolate the renal rabbit Kir6.1 although no signal for Kir6.2 could be detected. Inagaki et al. (22) found that uKATP-1 or Kir6.1 transcripts were expressed in all rat tissues tested: in the heart, ovary, and adrenals at high levels and in the kidney at low levels. Subsequently, Anzai et al. (5) found that Kir6.1 was expressed along the nephron except for the ascending and descending thin limbs. It appears that, in accordance with the intensity of Na+ reabsorption, Kir6.1 expression was as follows: PCT, medullary thick ascending limb > proximal straight tubule, CTAL, cortical collecting duct > OMCD > inner medullary collecting duct. Kir6.1 has been localized in cytoplasm and at the basolateral membrane of proximal tubule, CTAL, and collecting ducts. On the contrary, Kir6.2 mRNA seems to be absent in the kidney (19). In fact, the Kir6.2 subunit has been typically associated with pancreatic β-cells (4, 19, 36), cardiac and skeletal muscle (20, 32,36), smooth muscle (23), or brain (19,36). All of these results are in good agreement with evidence of the presence of Kir6.1 (and absence of Kir6.2) in PCT that was found in the present study.
Evidence for the presence of SUR2A and SUR2B in PCT.
With the same homology cloning strategy, we isolated from our proximal tubule cDNAs the rabbit renal SUR2A and its splice variant SUR2B; no signal could be detected with the degenerated PCR primer of SUR1. In agreement with this result, Inagaki and colleagues (19) found that SUR1 mRNA is absent in the kidney. However, using an RT-PCR approach as in the present study, Isomoto et al. (23) found a mouse SUR2B but not SUR2A signal in the kidney. This was also reported by Beesley et al. (9), who found a PCR product for SUR2B but not for SUR2A or SUR1 in the mouse kidney. These authors also used an anti-SUR2B antisera that revealed specific staining of SUR2B in distal nephron segments of mouse kidney, and a diffuse, low-level staining was observed in proximal tubules. In contrast, the rat kidney homologue of SUR2B was recently isolated and shown to be abundantly expressed in rat proximal tubules (41). Beesley et al. (9) found that no protein could be detected with anti-SUR2A antiserum in Western blot studies, and no staining could be observed in the immunohistochemistry at dilution of antisera equivalent to that used with anti-SUR2B. Interestingly, at a lower dilution they found a low level of diffuse staining in proximal tubules, which suggests that a low level of SUR2A could be present in the proximal tubule. We conclude that SUR2B is probably the main SUR transcript in the proximal tubule, with a lower level for SUR2A, which could explain the low level of staining observed at the protein level of SUR2A.
As it has been shown that Kir6.1 and Kir6.2 could coassemble to produce a functional K+ channel (13), it is possible to imagine that two different SUR subunits (SUR2A and SUR2B) could combine with Kir6.1 to form the proximal KATP channel. Such a coassembly would need to be proven at the protein level but would help in explaining the observed diversity of native KATPchannels.
Reconstitution of KATP Channels in Xenopus Oocytes With Kir6.1, Kir6.1/SUR2A, and Kir6.1/SUR2B
Expression of rabbit renal Kir6.1 yields a functional K+ channel.
Functional expression of Kir6.1 in Xenopus oocytes has revealed an unexpected result: contrary to a previous suggestion (14), the expression of an exogenous SUR subunit is not required to generate a KATP channel. Whole-cell currents of Kir6.1-expressing oocytes are significantly higher than those measured in control oocytes. However, the induced currents are <1 μM. This low current could be explained by the absence of an expressed SUR subunit. Indeed, it has been suggested, for example, that the SUR1 subunit could increase membrane insertion of the Kir6.2 subunit (25); however, we found that expression of Kir6.1 combined with the SUR2A or SUR2B subunit developed similar, quite-low K+ currents (Fig. 6). The high mean ATP level of healthy oocytes could also explain the low activity of these KATPchannels. Indeed, lowering the mean ATP level (by a 10-min treatment with sodium azide) increased the K+ current.
As expected for a K+ current, barium addition returned the conductance to the level of noninjected oocytes, and the inward currents induced by increases in external K+ concentration were significantly higher in Kir6.1-expressing oocytes than in control oocytes. In Kir6.1-expressing oocytes but not in control oocytes, a slight decrease in cytosolic ATP concentration induced a significant current increase. Finally, as for the native KATP channel, K+ currents of Kir6.1-expressing oocytes can be inhibited by injection of intracellular taurine. These different lines of evidence point to a significant KATP activity in Kir6.1-injected oocytes. It remains to be shown whether the oocyte can provide an endogenous SUR subunit to form a complete KATPchannel or whether such a subunit is unnecessary for promoting a KATP channel activity. However, the presence of a sufficient level of endogenous SUR subunits to form a KATPchannel with the overexpressed Kir6.1 is doubtful, because the K+ current of Kir6.1-injected oocytes is insensitive to glibenclamide.
The present study shows that coexpression of Kir6.1 with SUR2A induced a glibenclamide-sensitive K+ current in oocytes. These results are at variance with previous work, which suggests that this combination failed to induce a significant channel activity (2). On the other hand, our results (45) with expression of Kir6.1 and SUR2B confirmed earlier results in HEK293T cells that this subunit combination was fully capable of generating a functional K+ channel.
Comparison Between Regulatory Properties of Cloned Rabbit KATP and Known Characteristics of Native KATPChannels in PCT
Expression of Kir6.1 in Xenopus oocytes has previously been shown to develop a K+ channel with a 70-pS conductance, whereas Kir6.1 combined with SUR2B produces a 29–33-pS K+ channel in HEK293 cells (13,45). It remains to be shown whether the expression of Kir6.1 with SUR2A and SUR2B could be responsible for a native 50-pS KATP channel in the rabbit proximal tubule. Comparison of the conductances of native KATP channels with those of Kir and SUR subunits expressed in heterologous cells (for review, see Ref.6) has already shown some discrepancy. However, focusing on the comparison of the specific properties of the proximal tubule KATP channel with the characteristics of the cloned Kir6.1/SUR2A and/or Kir6.1/SUR2B expressed in oocytes, our results suggest that the isolated clones are good candidates for a native KATP channel in PCT.
The best evidence that Kir6.1 could be involved in the PCT KATP is its taurine sensitivity. Indeed, we recently found that the native KATP channel of the proximal tubule was inhibited by intracellular taurine (31). Several physiological roles have been identified for intracellular taurine, including modulation of Na+, Ca2+, or Cl− transport (for review, see Ref. 18), but taurine sensitivity of the K+ channel is a relatively new finding. Direct inhibition by taurine of the KATP channel has been also shown in guinea pig and rabbit ventricular cardiomyocytes (16, 37). More recently, experiments (42) on skeletal muscle fibers have shown that taurine stabilizes the close state of the KATP channel. In addition, it has been found (42) that taurine could increase glibenclamide affinity, which suggests that taurine could interfere with the glibenclamide site on the SUR subunit or on the Kir subunit at a site allosterically coupled to the SUR subunit. We now demonstrate that the cloned renal rabbit Kir6.1 expressed in Xenopus oocytes develops K+ currents that are sensitive to intracellular taurine, which suggests that the taurine sensitivity of the KATPchannel does not require the presence of an expressed SUR subunit. Finally, we recently found (10) that the endogenous, ATP-sensitive K+ channel in Xenopus oocytes, which was activated when ATP levels were decreased below 1 mM, was significantly inhibited by intracellular taurine.
Until now, the only K+ channels reported to be taurine sensitive were KATP channels. Testing the effect of taurine on different K+ channels from the Kir family, we have demonstrated that taurine sensitivity is not a common characteristic of the Kir family but is a specific property of KATP channels.
Taurine sensitivity is particularly interesting in the context of the proximal tubule, which is subjected to frequent changes in cell volume in response to variations in transepithelial Na+ transport (27). If taurine can be shown to be an exportable osmolyte in PCT as for other tissues (15, 28, 34, 40), a PCT cell that is initially swollen by excessive apical Na+ uptake could react by releasing its intracellular taurine. This decrease in intracellular taurine concentration would activate basolateral KATP channels. In this way, loss of intracellular osmolytes and activation of a K+ current would act in concert to efficiently regulate PCT cell volume.
In rabbit PCT, Tsuchiya et al. (43) found that a high concentration of glibenclamide (IC50 of 250 μM) was needed to inhibit the basolateral KATP. The absence of SUR1 is consistent with this low sensitivity, as SUR1 is characterized by a glibenclamide affinity on the order of 1 nM (3, 19). Interestingly, SUR2A and SUR2B are low-affinity receptors that require 100–1,000-fold higher glibenclamide concentrations to inhibit the channel (20, 23). Identification of the presence of SUR2A and SUR2B in the present study is in qualitative agreement with the low sensitivity observed for the basolateral KATP of rabbit PCT. In addition, expression of Kir6.1 with SUR2A or SUR2B results in the development of K+ currents that are sensitive to micromolar concentrations of glibenclamide (such as 50% inhibition of the Kir6.1/SUR2A current with 50 μM glibenclamide).
In summary, cDNA for Kir6.1, SUR2A, and SUR2B were found in a rabbit PCT cDNA library, whereas Kir6.2 and SUR1 appeared to be absent. Expression of Kir6.1, Kir6.1/SUR2A, and Kir6.1/SUR2B inXenopus oocytes induces K+ currents that are sensitive to external K+, external barium, cytosolic ATP, and intracellular taurine; all of these properties were previously found for the native KATP channel. This suggests that the KATP channel of rabbit PCT could be formed from a combination of Kir6.1 with SUR2A and/or SUR2B. This suggestion must be further tested at the protein level.
The authors acknowledge S. J. White, R. Sauvé, H. Van Tol, L. Salkoff, and S. Seino who graciously provided the different Kir clones.
This work was supported by the Medical Research Council of Canada Grant MT-10900 to J.-Y. Lapointe and R. Laprade. E. Brochiero acknowledges a postdoctoral fellowship from the Ministère de l′Education du Québec.
Address for reprint requests and other correspondence: J.-Y. Lapointe, Département de Physique, P.O. Box 6128 Succursale "Centre-ville," Montréal, Québec H3C 3J7, Canada (E-mail: jean-yves.lapointe{at}umontreal.ca).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Copyright © 2002 the American Physiological Society


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President John Mahama, has condemned the Xenophobic attacks in South Africa, describing it as a hindrance to the much touted Africa's integration agenda.
The Ghanaian President and Chairman of the Economic Community of West African States (ECOWAS), Mr. John Mahama has asked the South African government to immediately put a stop to xenophobic attacks of fellow Africans and to ensure that perpetrators are brought to book.
Mahama who spoke to Journalists shortly after a congratulatory visit to Nigeria's President- elect, General Muhamnadu Buhari in Abuja, described as very regrettable, the attacks by South African youths on other African citizens living in their country.
"I think that the government must sit up and must take strong action and those that have been involved in these atrocities must be brought to book and must be punished serving as a deterent so it does not happen in future," he said.
While recalling the contributions of African countries, especially those considered as 'frontline states', like Nigeria, Mahama said it is regrettable that the same people who fought against apartheid are being attacked.
He said though Nigeria is not a neighbour of South Africa, the country was considered a frontline state because of her economic contribution to the fight to liberate South Africa from apartheid.
"I think it is an issue that we are all worried about because of the specific circumstances of South Africa and its most regrettable and most unfortunate, I think that the young people of South Africa do not know what happened before they gained their freedom, the whole of this continent stood behind South Africa, the whole of Africa stood behind South Africa to fight against apartheid.
"I remember all of us who growing up as secondary school children went on marches and as part of the African Youth command boycotted classes and all that all in the fight against apartheid.
"Indeed, for several of the countries whose citizens were brutalised in South Africa, these are countries that were called front line states and harboured the freedom fighters of South Africa and gave them safe haven, gave them passports to be able to avoid the clutches of the apartheid regime and even Nigeria,
" It is regrettable that the same people who fought against apartheid are being attacked. The pictures we have seen are horrible, As ECOWAS we have issued a statement condemning what is happening, The unfortunate thing is this is not the first time, it keeps flaring up and so while we are condemning this incidence, we must work with South African government to ensure that it won't happen again, We are trying to create an integrated continent where our people can move freely amongst our countries.
"This has not set a very good example for integration and especially for South Africa that has investments all over countries," he said
Speaking on the conduct of the last election, Mahama said the polls has adjudged very peaceful, free, fair and transparent.
"Nigeria is the biggest economy in West Africa and is the most populous and also the biggest economy in Africa so it is a very valued member of ECOWAS and we will continue to expect that Nigeria would show a certain leadership and carry her responsibility in terms of the work of west African states.
He said, he had earlier met with President Jonathan where he commended him for his maturity and statesmanship in conceding defeat before the tally was done.
He also said Ghana and Nigeria have very close relationship and we will continue to work closely with Nigeria, we hare the same values our cultures are similar...
"I think that Nigeria has shown a good example for self regime that democracy and good governance have found a firm root in the ECOWAS, the ECOWAS has a protocol on democracy, good governance and elections and I believe that has been properly followed here in Nigeria.
"We have five elections this year and Nigeria has set the pace and we still have Togo that is coming on Saturday 25th and in October we have Burkina Faso, we have cote d ivoire, we have guniea, so I think that with what has happened in Nigeria it is an example for other countries in terms of the standard electioneering.


text: Share ASIS International / Store / Products Executive Roadmap to Fraud Prevention and Internal Control, 2nd Ed Martin T. Biegelman and Joel T. Bartow Wiley Item #:2077 Published:2012 Pages:440 ISBN:978-1-118-00458-6 Member:$30.00Nonmember:$33.00 Add to Wish List Clearance: original price $45 member, $50 nonmember Now in a second edition, this practical book helps corporate executives and managers understand the full ramifications of good corporate governance and compliance. It covers best practices for establishing a unit to protect the financial integrity of a business; theories and models on how and why fraud occurs in an organization; importance of strong internal controls; major compliance and corporate governance initiatives and milestones since 1985; and more. Complete coverage includes implementation guidance for a robust fraud prevention and compliance program including sample policies, best practice examples, and a 14-point management antifraud program. Features: Covers fraud risk assessment and prevention guidance Looks at global risk issues, including the Foreign Corrupt Practices Act (FCPA) and UK Bribery Act Examines amendments to the Federal Sentencing Guidelines for Organizational Crime Discusses Dodd-Frank Whistleblower Provisions Explores enterprise risk management key program elements Offers coverage of how fraud and compliance failures contributed to the financial crisis Includes enhanced principles for fraud data mining Presents new cases, checklists and real-world examples, expanded international coverage, and the latest technological tools Shows executives and managers what their responsibilities are regarding fraud prevention, internal controls, and compliance Provides an instructor's website, including a test bank Completely revised and updated, Executive Roadmap to Fraud Prevention and Internal Control, Second Edition is every manager's best resource for understanding all the complex issues and responsibilities associated with fraud and compliance. Reviewed in Security Management, 2/15. Format: Hardcover Page Content Cart Summary Cart Summary Items in Cart: 0 Cart Total: $0.00 View Cart Checkout Related Items


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Thanks to EJC's Clinic Volunteers For a Great Year So Far
As our annual Labor Day Awards Breakfast approaches, the staff of the EJC wants to give a great big THANK YOU to all our loyal intake volunteers and advising attorneys who make the EJC's Workers' Rights Clinics such a valuable resource to DC-area low-income workers. Intake volunteers like Tammy Craig, a legal assistant at WETA TV, and advising attorneys like Patrick Riley, a retired labor lawyer, have provided advice and consolation in over 1,050 intakes so far this year. We are thrilled to be able to honor Tammy and Patrick at the Labor Day Breakfast this year!
At this pace, the EJC will conduct over 1,600 intakes in 2015, the most since at least 2009. For all our volunteers, behind such a number are the dozens or even hundreds of individuals they've served at the clinics. Tammy began volunteering at EJC's clinic in southeast Washington in 2013, and has since volunteered regularly, including at EJC's new clinic in Maryland. "I started off with the clinic when I was unemployed, looking to serve myself by serving others," Tammy said. "But I ended up getting so much more out of it, learning from the workers and the lawyers who serve them." For her, volunteering at the clinic has been, in a word: "awesome."
Tammy's work and those of her fellow volunteers has allowed the EJC to expand its reach this year. We now have aSaturday clinic at Bread for the City in Southeast Washington, for workers whose schedules make it difficult to attend a clinic during the week. We've collaborated with the Neighborhood Legal Services Program (NLSP) to provide free legal help at one of NLSP's Southeast locations twice per month. And working side-by-side with the Prince George's County chapter of the NAACP, we've experimented for the first time with a clinic location in Maryland.
Thanks to all of our volunteers and supporters for your help so far in 2015! You are the backbone of the EJC's work to provide assistance to low-income workers each day. We most definitely could not do it without you!
With gratitude,
The EJC Staff
To learn more about EJC's clinics, including how to volunteer, click here.


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text:
The PR manager at Orange UK says he's "just heard" the Samsung Omnia 7 will be HD voice enabled on its UK network.
Conor Maples (@conorfromorange) is the official "voice" for UK Orange; other details weren't available via the twitter feed, but last week Orange lined up solidly behind the Windows Phone 7 announcement. The company is "exclusively" offering the HTC 7 Mozart as well as offer the Samsung Omnia 7 in the UK starting on October 21.
Slashgear is reporting that HTC has "no plans" to add HD voice to the HTC 7 Mozart – which is interesting since the technology should be a codec drop-in and HTC is said to be offering HD voice via one or more platforms by the end of the year.


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PurTest Bacteria Test is a do-it-yourself EPA based test that allows you to screen your water for dangerous levels of bacteria, Test for Ecoli (Escherichia Coli) and coli form bacteria which if present, indicate the possible existence of harmful bacteria. Add water sample to the test vial that includes the reaction media, shake and set aside. A color change from purple indicates unsafe conditions. Easy, reliable, fast, accurate, convenient. Nothing to mail, everything you need is included in the test. A free test for Nitrates and Nitrites is included with the test.
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The Collected Tales of Nurse Matilda Paperback
by Christianna Brand
Illustrated by Edward Ardizzone
"Once upon a time there was a huge family of children; and they were terribly, terribly naughty." So begins "Nurse Matilda", the first of three books about the no-nonsense nanny who uses magic to rein in the mischievous children in her charge - and changes their lives for ever.
- Format: Paperback
- Pages: 384 pages, Illustrations
- Publisher: Bloomsbury Publishing PLC
- Publication Date: 05/11/2007
- Category: General
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Showing 1 - 1 of 1 reviews.
Review by jfoster_sf
"Once upon a time there was a huge family of children; and they were terribly, terribly naughty." The first book was great! The narration was perfectly funny and I just loved it. I think this book is best for reading aloud to young kids, they will love how naughty the children are and how Nurse Matilda makes magic happen, and try to keep track of how many kids there are-- "There were so many of them (children) that I shan't even tell you their names but leave you to sort them out as you go along, and add up how many there were." When the book ends, all the children are now well behaved and no longer need Nurse Matilda, so she leaves to help another group of naughty children. How can there be two other books if the kids are good now? It turns out that in the second book, the kids have all but forgotten Nurse Matilda and are all naughty again! And their parents have adopted a ton of children so there are even more! Nurse Matilda comes back and the whole thing starts over again (with many of the same phrases and very similar scenarios.) I think that young kids might not mind the similarities and repetitive situations (maybe 5 and 6 year olds?) but I think older kids would get bored. I ended up not finishing book 2 and didn't bother with book 3, but I still love book 1 which is what my rating is based on.
Also by Christianna Brand


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Bring your children for a kids' yoga session held at the Parc de la Ciutadella every Wednesday.A kids' yoga class that takes place in the Parc de la Ciutadella is a refreshing change. For kids aged four to seven years, the outdoor sessions offer a chance for kids to enjoy some fresh air whilst enjoying music and movement. The yoga poses for this age group are typically done with an animal in mind. Stories and games using animals are also used as a source of inspiration. As well as developing flexibility and coordination, kids can also increase their level of concentration, self-discipline and learn breathing techniques that they can use for life.
Children need activities that keep them going and do not bore them, as they easily loose attention and interest. We create an environment that invites them to remain interested and energetic. Therefore we mix various activities like movements, singing, dancing, story telling, breathing and each class to finish off with relaxation.
At times we will use music to do movements and at times we will ask the children to create their own music.
The benefits of yoga:
· Develop flexibility, coordination, balance, body alignment, strength and stamina
· To enhance physical and mental health
· Increase level of concentration, self discipline, inner strength and clarity
· To learn breathing techniques which gives us the tool to regulate our life when facing various situations, and to remain calm and focused
· Learning to be respectful and cooperative to family members and friends
· Promoting positive communication and good listening skills which gives self respect, compassion and understanding for others needs.
· Bring the creative side out through storytelling, arts and crafts and body movements
· Building self-confidence and self-esteem.
Where: Parc de la Cituadella (next to the play ground by The Zoo entrance).
When: Wednesdays at 6.00pm.
Age: Four - seven years old
Cost: Donations or free if you like.
Tel: +34 620 072 613
Information supplied by Kids in Barcelona
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I want to invite you to join me on a journey. You've already set sail on a grand voyage into the world of 21st Century Learning. But, I've found that every great adventure should include at least a few side destinations. You know, those little trips that you didn't plan to take when you started out, but somehow become part of the itinerary? If you're like me, it's those side journeys that add depth and meaning to your travels more than the final destination.
The journey we'll be embarking upon is one that speaks to the heart of becoming a citizen in this global, digital, hyper-connected world we inhabit. I'd like to explore with you how to brainstorm, design and implement projects where collaborative learning is paramount. To accomplish this, we'll do many things including:
• take a tour of successful projects and what makes them tick,
• explore the process of matching outcomes to engaging activities, and
• learn skills that encourage collaboration and communication.
What I'd like for you to see me as is a fellow traveler. My paths have taken me to many places over my 20 years in teaching and I'd like to share some of the tales and lessons I've learned during those years. I've given you a little background information about those journeys here, but I invite you to join me on my blog, on Twitter or in Plurk to see and hear what makes me tick. I hope that you'll be willing to share your tales too, because no journey is as fulfilling as when you have someone to travel the miles with you.
Of course, there's plenty of research and best practices out there to study but there's also nothing like knowing in your heart what works best because you've lived it in a classroom full of students. So, I look forward to hearing from you, learning with you, and someday looking back to reminisce about the adventure we had.
A word of caution. This adventure may delve deep into ideas and resources that go beyond how to use a web tool to design a lesson. If you'd like to expand your horizons or know what you'll be getting into before you step onto the tour bus, check out the ideas that Randy Nelson shares in this video. To me, he speaks to the heart of what we'll be trying to learn.
Waypoint 1: As you reflect on Randy Nelson's definition of collaboration, share what classroom collaboration looks like to you.
Bonus points. Three books where I'll be gleaning ideas that have nothing to do with technology might be worth a read:
Training to Imagine – Kat Koppett
Made to Stick – Chip Heath and Dan Heath
Thinkertoys – Michael Michalko


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TDA Global Cycling is leading long distance tour operator in over 60 countries. Our tours are open to all who wish to take on the challenge. We have tours from two weeks, to multi-month expeditions that cross entire continents. Founded in 2002 by Henry Gold, we were chosen Best Adventure Travel Company at the Independent Travel Awards in 2015. The TDA Foundation, established at the same time, supports bike advocacy, donates bikes to individuals across Africa and encourages participating cyclists to raise funds for a charity of their choice.
At Berliner Fahrradschau we will be showcasing upcoming tours in South America, South East Asia, and Africa.


text: The last night of our cruise do we put our bags outside the door? We will be at Port Canaveral and have a noon return flight out of MCO. How quickly can we get off of the ship and on to the Disney shuttle? Should we do room service for our breakfast to save time? is the gratuity automatically added to our bill? How can we check our bill during the trip? When we go off of the ship for excursions, do we take our driver's licenses and passports, or just our licenses? We are traveling with 17 year olds. Do they also need to take their ID when we get off of the ship for excursions? I think these are my last questions. This is my first cruise and I am a bit nervous.


text: Video News: United Kingdom Syrians bomb ISIL forces, Moqtada sl-Sadr calls for a government for all Iraqis Fighting continues to spread in Iraq with a couple of new players making their entrance. Syrian warplanes are reported to have bombed ISIL militant positions in the town of Al Qaim, straddling the Iraqi-Syrian border and a key crossing point for the militant Sunni fighters. An earlier report said the Syrians had bombed ISIL within Iraq, but in any case the Syrian's move was welcomed by Iraq's prime minister.In Beiji the government released pictures of its forces in control of at least part of the country's biggest refinery. ISIL has been fighting for control of the facility for the past week. Baghdad says they have been completely pushed back.The second major player entering the conflict is the influential Shi'ite cleric Moqtada al-Sadr.He said: "First: fighting and terrorising civilians should stop. Second, the Iraqi government must fulfil the legitimate demands of moderate Iraqi Sunnis who suffered exclusion and marginalisation. And third, the formation of a national government with new faces which include all Iraqi faiths and rejects sectarian quotas must be speeded up."Al-Sadr's attempt to bridge the sectarian divide runs parallel with his ability to mobilise tens of thousands of Shi'ite fighters if needs be, and comes just a day after Prime Minister Nouri al-Maliki rejected the idea of an interim national unity government. © DailyMotion - Thursday, June 26, 2014


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text:
AIG and Goldman Sachs – How We Got Here from There
How screwed are we? It's worse than you think…
Following my long week of dogging the AIG executive bonus issues, I had planned to spend this day unwinding a little bit. Those plans were made before I spent the morning reading (and digesting) Matt Taibbi's latest Rolling Stone piece, The Big Takeover.
It'll take you awhile to read through the article, but after you're finished, I promise you that you'll have a better handle on the depth of the financial crisis this country is facing, why Fed chief Ben Bernanke is full of shit when he says "we'll see the recession coming to an end probably this year", and who the major players were that got us into this mess.
Here's your "Marie Antoinette moment" from Taibbi's investigation:
"We, uh, needed to keep these highly expert people in their seats," AIG spokeswoman Christina Pretto says to me in early February.
"But didn't these –highly expert people' basically destroy your company?" I ask.
Pretto protests, says this isn't fair. The employees at AIGFP have already taken pay cuts, she says. Not retaining them would dilute the value of the company even further, make it harder to wrap up the unit's operations in an orderly fashion.
The bonuses are a nice comic touch highlighting one of the more outrageous tangents of the bailout age, namely the fact that, even with the planet in flames, some members of the Wall Street class can't even get used to the tragedy of having to fly coach. "These people need their trips to Baja, their spa treatments, their hand jobs," says an official involved in the AIG bailout, a serious look on his face, apparently not even half-kidding. "They don't function well without them." … [emphasis mine]
Basically, Taibbi says, we're screwed.
The financial future of this country rests in the hands of a very few people who, ultimately, were at least partly responsible for getting us into this mess in the first place: Bernanke and Geithner, along with their ex-Goldman Sachs minions.
After reading Taibbi's lengthy piece, it's clear that there is absolutely no accountability for the strategies that have been put in place to solve the problems. Congress can hold all of the hearings that it desires, but neither Geithner nor Bernanke (or the unilateral policies of Treasury or the Fed) are answerable to congressional oversight.
If, as AIG CEO Edward Liddy claimed on Wednesday, AIG execs who received bonuses are really paying them back, it's not necessarily because they're trying to stave off the Marie Antoinette moment that's at hand (although that could certainly be a motivator), but because whatever bonus money they're now receiving is literally WAM – walking around money – for these execs. Their bank accounts are already fat from spending your money at the Wall Street casino, and $2 or $3 or $6 million extra dollars just doesn't mean that much to them.
And no, there aren't going to be any scraps left at the table for you at the end of the day.
Update: Greenwald puts some wood on this one and hits it out of the park. And confidential to Joe Nocera: your douchebaggery is showing.


text:
Business TypeOther
Main MarketsWestern Europe
Product/ServiceReal Estate Agents
Business OwnerPierrette
EmployeesLess than 5 People
CategoryConstruction & Real Estate - Real Estate
Company TagsAndaluz - Costa De La Luz - Dream Estate
Company Introduction
Andalucian dream. . . . Estate agent on the costa de la luz where tourism has not yet taken off. Beauty and peace amongst history, culture and traditions. We are professional and we owe our good reputation to people like you, trusting us in buying and selling properties. In this wonderful part of Spain.
Contact Information
Contact PersonMs. pierrette collard
Fax Number34-956-446341
Post Code11149
AddressAvda Holanda 72, Roche Residencial, Conil De La Fra, Cadiz, Spai
Online MapSueno Andaluz S.L. Map & Directions


text: Has anyone used their Galaxy S as a tethered modem without installing Kies? According to the manual, you can just set the phone's USB settings to "PC Internet" then plug it into the computer. Supposedly after that you just follow "on screen instructions" to install the phone as a modem (presumably the add new hardware wizard). Has this worked for anyone? I tried it on two computers and the hardware wizard failed. Does anyone know where to download the necessary drivers? Apparently installing Kies installs the drivers needed, so you can then tether the phone without running Kies. The problem is that Kies requires an internet connection to install, so even if you carry around a kies install on the phone, you end up in a catch-22. All of this was done on XP pro SP3. I have an international I9000 with ZSJF7 baseband.


text:
Kelly Rutherford feels like her children's "voices have not been heard."
The former 'Gossip Girl' star, who has been embroiled in a bitter international custody battle with German ex-husband Daniel Giersch over their son Hermes, eight, and daughter Helena, six, since their split in 2008 and was forced to allow them to return to his home in Monaco after a court hearing in New York on Tuesday (11.08.15), thinks there needs to be better laws in place to protect them and other children in similar positions.
The 46-year-old actress said: "You're being vocal not only for your children -- this is happening to so many people. I have people stopping me on the streets, writing me letters, sending me envelopes of their cases... There needs to be laws in place. You're setting the kids up for a problem, the parents up for a problem. I shouldn't have to fight this in a foreign court.
The hearing was held earlier this week after Kelly refused to fly her children back to Monaco last week, as previously agreed, and Daniel, whose U.S. visa was revoked a few years ago, accused her of child abduction.
But she told 'Good Morning America': "He was in communication with them every day. You know, I talked to my lawyers, they were saying, this is concerning on many levels.
"I walked into a courtroom where everything felt like it was already done. It was a done deal. And his mother was sitting there with plane tickets, smiling, ready to take them. Nobody had heard our argument."
The actress previously branded Judge Ellen Gesmer's recent ruling "shocking, illegal and abusive" and accused her of breaking the law by ordering her to send her children, who were both born in America, back to Monaco.


text:
Stephen Hawking Boycotts Israel 'On the Advice of Palestinian Academics'
Extremely sad and disappointing news from Cambridge University.
JERUSALEM: Stephen Hawking has pulled out of a high-profile conference to be held in Jerusalem in June to support an academic boycott of Israel, conference organisers and the university said on Wednesday.
The academic and cultural boycott, organised by international activists to protest against Israel's policies toward the Palestinians, is a heated and contentious issue; having the renowned physicist and cosmologist join it is likely to help the anti-Israel campaigners significantly.
"Never has a scientist of this stature boycotted Israel," said Yigal Palmor, the spokesman for Israel's Foreign Ministry.
Organisers of the fifth annual Israeli Presidential Conference, held under the auspices of President Shimon Peres, said they had received a letter over the weekend from Professor Hawking announcing his decision.
Cambridge University issued a statement indicating that Professor Hawking had told the Israelis he would not be attending "based on advice from Palestinian academics that he should respect the boycott", Associated Press reported.
Looks like Hawking can't sort good advice from bad. The boycott is aimed, ultimately, at killing academic freedom.


text:
Nogibingo! 7 Episode 2 English Subtitle
Hello guys!
We did a collaboration with Tainted Wings Fansub (TWFS) to release the sub!
Original translation : Good Enough Subs
Additional translation : Za-Kuuru Subs
Encode, Typesetting, (timing fix, rough check) : BlackSwan
Streaming: DailyMotionSubtitle Font : Omniscript W01
Softsub (translation only) : Here
Softsub (translation only) : Here


text:
Traveling Luck for Olastøl, Hordaland, Norway
Where is Olastol?What's around Olastol?
Wikipedia near Olastol
Where to stay near Olastøl
The timezone in Olastol is Europe/Oslo
Sunrise at 08:48 and Sunset at 15:48. It's light
Latitude. 60.5333°, Longitude. 6.6333°
Weather near Olastøl; Report from Sogndal / Haukasen, 79.2km away
Weather :
Temperature: -4°C / 25°F
Wind: 3.5km/h Northeast
Cloud: Scattered at 1000ft Scattered at 2300ft
Weather :
Temperature: -4°C / 25°F
Wind: 3.5km/h Northeast
Cloud: Scattered at 1000ft Scattered at 2300ft
Satellite map around Olastøl
Loading map of Olastøl and it's surroudings
Geographic features & Photographs around Olastøl, in Hordaland, Norway
- populated place;
- a city, town, village, or other agglomeration of buildings where people live and work.
- Folkedal (4.1km)
- Eide (4.9km)
- Seim (4.9km)
- Granvin (5.2km)
- Nesheim (5.5km)
- Hause (6.2km)
- Kvanndal (6.2km)
- Hamre (6.2km)
- Spildo (6.6km)
- Kjerland (6.8km)
- Rong (9km)
- Lussand (9.3km)
- Tjoflot (9.9km)
- Naustflot (9.9km)
- Fenno (10.1km)
- Djønno (10.4km)
- Rjoo (10.5km)
- Kaland (10.6km)
- Opeland (11km)
- Litlere (11.4km)
- Åkre (11.5km)
- Hesthamar (12.5km)
- Skutle (12.6km)
- Lote (12.8km)
- farm;
- a tract of land with associated buildings devoted to agriculture.
- peak;
- a pointed elevation atop a mountain, ridge, or other hypsographic feature.
- Grønahorgi (7km)
- Grim (8.7km)
- Gråfjell (8.8km)
- Midnuten (12.8km)
- railroad station;
- a facility comprising ticket office, platforms, etc. for loading and unloading train passengers and freight.
- Granvin (4.9km)
- Skjervet (6km)
- Flatlandsmo (8.4km)
Accommodation around Olastøl
- mountain;
- an elevation standing high above the surrounding area with small summit area, steep slopes and local relief of 300m or more.
- Herdabreida (7.9km)
- Oksen (8.4km)
- Grubbafjell (11.8km)
- administrative division;
- an administrative division of a country, undifferentiated as to administrative level.
- Granvin Herad (5.2km)
- Voss Herad (11.1km)
- fjord;
- a long, narrow, steep-walled, deep-water arm of the sea at high latitudes, usually along mountainous coasts.
- Granvinfjorden (9.9km)
- valley;
- an elongated depression usually traversed by a stream.
- Bordalen (10.5km)
- cirque;
- a bowl-like hollow partially surrounded by cliffs or steep slopes at the head of a glaciated valley.
- Roksbotn (12.8km)
- marine channel;
- that part of a body of water deep enough for navigation through an area otherwise not suitable.
- Utnefjorden (10.6km)
- lake;
- a large inland body of standing water.
- Granvinvatnet (5.2km)
Wikipedia entries close to
- Granvinsvatnet lake
- Granvin city city m
- Lote city city o
- Utne city city o
- Vossevangen city city o
- Vangsvatnet lake
- Bjølsegrøvvatnet lake
- Lønavatnet lake
- Torfinnsvatnet lake
- Voss (Norwegen) city city i
- Hardanger landmark landmark
- Botnen, Hordaland city city o
- Hamlagrøvatnet lake
- Ulvik city city m
- Ullensvang city city l
- Eidfjordvatnet lake
Airports close to Olastøl
Sogndal haukasen(SOG), Sogndal, Norway (79.2km)
Bergen flesland(BGO), Bergen, Norway (87.7km)
Soerstokken(SRP), Stord, Norway (116.5km)
Floro(FRO), Floro, Norway (154.5km)
Fagernes leirin(VDB), Fagernes, Norway (163.9km)
Airfields or small airports close to Olastøl
Boemoen, Bomoen, Norway (14.6km)
Dagali, Dagli, Norway (110.8km)
Bringeland, Forde, Norway (113.2km)
Notodden, Notodden, Norway (191.3km)
Photos provided by Panoramio are under the copyright of their owners.


text:
Heavy Duty Weed Wiper
From Weed Wipers
The GrassWorks Weed Wiper Heavy Duty Unit is popular with Soil and Water Conservation Districts, cattle associations, farm supply stores and feed stores for rental application.
Most popular related searches
Customer reviews
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text:
myWebDNS is a MySQL/PHP Web-based package to
manage a DNS server configured with Bind. It
permits administrators to create and manage the
DNS, and users to create and manage the domains.
28 Feb 2002 06:05
A Fluent OpenStack client API for Java.
A TWiki appliance that is easy to use and lightweight.


text:
Eye play by CravingDovesWatch
©2012-2017 CravingDoves
What do you think?too much?
It's cute! I really think you would do more portraits! Your really good!
lol yeah but the camera scares me!lmao pfft
lmao! Yeah it scars me too
Yeah its feel like it makes you a lot more judgemental about your appearance!When its pointing on yourself but it doesn't feel that way when your the one aiming it!


text: Where can I get froyo?! I am not getting the ota and I was hoping someone had the leaked version. Can anyone point me towards it? I have a custom rom so I won't get ota so I really need the leaked version of froyo for lg ally. Any help wud b great.


text:
Some venture the premise that New York SETS the trends when it comes to style, stature (did he mean statue?) and insight. The eyewear spied here certainly empowers that opinion. Be it a bold sport-inspired shade scanning the view from the Staten Island Ferry, a tulip-loop
sunglass baring its classy cutting-edge lens or a wise, white-locked rocker showing off his owl-eyed circle specs, there is ample proof here that New Yorkers set the seen.
—James J. Spina


text:
Your browser does not support iframes.
Several area middle school students will be part of a delegation from Virginia participating in a People to People Leadership trip to Australia this summer.
Virginia's General Assembly convenes today in its biennial "short session" in which it tweaks the two-year budget adopted the previous year.
Bedford's Alzheimer's support group has folded. The group held its last meeting in November, according to Cindy BonDurant. BonDurant is regional director for the Central and Western Virginia Chapter of the Alzheimer's Association.
BonDurant said that the Bedford group, which held meetings on the third Monday of each month at 3 p.m., had zero attendance month after month for the last two years. That mystifies her.
Some things need to change
I read the article in last weeks paper about the cock fighting.
The Humane Society of the United States is a wonderful organization that fights to protect animal rights and has support from people from all walks of life that send whatever donation they can.
People now have access to newspapers, T.V. and the Internet and know more of what is going on than they did years ago.
Bedford City Council will have plenty on its plate the next year as it considers whether to revert to town status and works to balance a budget in these tough economic times. Monday night council officially began its work for the year by swearing in those council members who were elected in November — including first-time member Steve Rush — and by re-electing Skip Tharp as the city's mayor.
A state grant is making it possible for the Bedford Volunteer Fire Department to install free smoke detectors.
The grant is from the Virginia Department of Health and has allowed the fire department to buy 500 smoke detectors. It also paid for tools to install the detectors and nine volt lithium batteries, according to Kenny Taggart, who is heading up the program. Taggart said that the grant requires these batteries, allegedly good for 10 years, rather than less expensive batteries.
With Bedford County Schools expected to receive about $5 million less in state funding than last year, this year's budget process is expected to be a challenge. That process will get underway this week as the school board holds a work session Thursday afternoon and then a public hearing on the budget that evening.
"We're looking at almost every single line item and every program," stated Randy Hagler, director of finance for the school system. "It's going to be a pretty difficult year."
Virginia's General Assembly will face a serious budgetary challenge when it convenes in Richmond on Jan. 14.
"The picture is not pretty," commented Delegate Lacey Putney, chairman of the House of Delegates Appropriations Committee.
The Appropriations Committee, one of 14 standing Committees of Virginia's House of Delegates, has jurisdiction over state budget matters, according to the committee's Web site.
A Bedford County man facing charges for selling roosters for cockfighting will have to post a bond of $8,000 if he hopes to get the 40 birds confiscated from his property back.
A Bedford County man is facing charges for selling roosters for cockfighting, following his arrest last week as part of a pre-Christmas round-up of criminals in the county.
Copyright © 2017
The Bedford Bulletin is your source for local news, sports, events, and information in Bedford County and Bedford, VA and the surrounding area.


text:
The Tao Of Arthur*
1) Start Slowly...Taper Off.
2) Everything You Know Is Wrong.
3) No Matter Where You Go, There You Are.
3a) But there's no there there.--G. Stein
4) So Near, And Yet...So What?
4a) It's a one-shot deal--no second chances.--William Burroughs
5) Give me the strength to change the things I can, the grace to accept the things I cannot, and a great big bag of money.
6)Paranoia is just having all the facts.--William Burroughs, again
6a) Just because you're paranoid doesn't mean they're not out to get you.
7) If it ain't broke--break it.
8) If work were such a splendid thing, the rich
would have kept more of it for themselves.
9) "Things are more like they are now
than they ever were before." --Ike
10)The trouble with our times is that the future is not what it used to be.
11) I am not sincere, even when I say I am not.
(Alternate: You've no idea what a poor opinion I have of myself, and how little I deserve it.)
*Remember, this life is a test. This is not an actual life. This is only a test. If this had been an actual life, you would have been given further instructions on where to go and what to do.
And, remember the words of the prophet:
"I came to a fork in the road, and I took it."
SOCIETY, POLITICS, MUSIC, WHIMSEY and FREE SHAMWOWS. There's so much bad in the best of us, and so much good in the worst of us, that it hardly behooves any of us to talk about the rest of us. But I'll do it anyway. Stay tuned for social and political news and commentary that you won't find anywhere else. I know, I've looked around. All other blogs are empty, vapid wastes of time. Mine will not be empty.
Sunday, January 16, 2005
The Tao of Arthur
Posted by Arthur at 3:54 PM
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