Toni Thorpe, a long-standing and experienced agent in the sale ofcountry and equestrian property throughout Essex, has joined theleading specialists, Zoe Napier Country & Equestrian.
This is considered a very popular move for Toni (pictured right),by Zoe herself and also many longstanding clients who believe thatthe new team of key players, Zoe Napier, Eve Reed and now, Toni,offer an unrivalled and heavily bespoke service.
Zoe Napier …
ALBANY, N.Y. - Rat poison was found in pet food blamed for the deaths of at least 16 cats and dogs, but scientists said Friday they still don't know how it got there and predicted more animal deaths would be linked to it.
After the announcement, the company that produced the food expanded its recall to include all 95 brands of the "cuts and gravy" style food, regardless of when they were produced. The company also said it would take responsibility for pet medical expenses incurred as a result of the food.
The substance in the food was identified as aminopterin, a cancer drug that once was used to induce abortions in the United States and is still used to kill rats in some …
Worshippers in eight dioceses around the country have banded together in a last-ditch effort to ask the Vatican to instruct bishops to negotiate with them over the closures of their parishes and to stop them from "wrecking the Catholic Church in America."
Peter Borre, co-chairman of the Boston-based Council of Parishes, formed in 2004 to oppose parish closings, was in Rome on Monday to hand-deliver a letter asking that the Vatican tell bishops to promptly enter into mediation with 31 parishioner groups in Allentown, Pennsylvania; Boston; Buffalo, New York; Cleveland; New Orleans; New York City; Scranton, Pa.; and Springfield, Massachusetts.
The …
The second drought in four summers has left most area homeownerseither with brown grass or high water bills.
But a hardy southern grass that's creeping north can giveChicagoans green grass with no sprinkling.
The grass, called tall fescue, sends its water-seeking roots asdeep as 6 feet. By comparison, roots of Kentucky bluegrass and ryegrass blends common in the Chicago area grow less than 2 1/2 feetdeep, seed company president Jon Loft said Sunday at the NationalHardware Show at McCormick Place.
"Tall fescue has really caught on in Ohio and southern Indiana,and there's no reason it can't catch on in Illinois," Loft said."When you have heat and no …
NEW YORK (AP) — B.J. Upton and Carl Crawford each drove in two runs in a seven-run sixth inning as the Tampa Bay Rays punished CC Sabathia in his much-anticipated rematch with David Price in a 10-3 win over the New York Yankees on Thursday.
Price (18-6) labored through six innings but Sabathia (20-7) struggled even more. The Rays beat New York for the second straight day, splitting the four-game set and pulling within a half-game of the first-place Yankees in the American League East.
Yankees reliever Javier Vazquez equaled a big league record by hitting three straight batters in the seventh as the Rays added two runs without getting a hit.
Ten days earlier, Sabathia and …
Colorado Rockies reliever Matt Herges says he's actually glad he was implicated in the Mitchell Report on doping in Major League Baseball because it led him to clear his conscience over his "dirty little secret."
In the report, former New York Mets clubhouse attendant Kirk Radomski said Herges bought human growth hormone on two or three occasions in 2004-05, when Herges was with San Francisco and Arizona. Herges said he used it in the offseason.
"I didn't used to be this way, but I'm at the point where I know what I did was wrong 100 percent, no excuses, no justification, no rationalization. I screwed up and I crossed the line," the …
'The Mysteries of Harris Burdick'
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In his many children's books, author-illustrator Chris VanAllsburg looks at the world from unexpected angles, transforming thefamiliar into the vaguely grotesque, the ordinary into the eerie. Hisdrawings and text meld into a wonderland of the possible andimpossible.
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Some customers may comment that the sliding side door is hard to open. The door trim panel may be contacting the primary seal in the lower corner.
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A severe storm struck the building hosting the U.S. swimming trials, damaging the complex and cutting short practice Friday.
Chunks of the building were ripped off and water poured down the steps at one end of the seating area, flooding the floor around the competition pool.
Superstar Michael Phelps and hundreds of swimmers were ordered out of the water and into interior hallways, cutting short their workouts. The building was later closed for the night to assess damage and make repairs in time for Sunday's start of the eight-day trials.
There was no structural damage, although the arena lost insulation and sustained water damage, building …
CB2 started life as a Crate and Barrel for people too young, hipand penny-pinching to shop at parent Crate and Barrel. Now it has acatalog -- just like a real store! -- a clever Web site, and justthis week it started a gift registry.
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In the early morning hours on Monday, the lives of three young Black men were extinguished by an act of murder. They died where they lived, on the 400 block of East 78th Street in the Chatham neighborhood, just steps away from where they were raised and schooled.
Across the street from the grass-lined walkway where Jemez L. Nunley, 29, John Montgomery, 31, and Darryl Dentley, 36, were murdered, stands a cathedral where members of the community worship; and a few blocks away is Martha Ruggles Elementary School, the same school the three attended as kids.
But today, on the corner of 78th and Vernon, a group of the victim's loved ones and friends - most still living in the …
Jamie Meyer scored 49 points to help Abilene Christian overcome a 63-point effort by Renee Renz and beat Texas Woman's 147-143 in quadruple overtime on Monday night in a record-setting game.
The 290 combined points was an NCAA women's record for a single game. The 143 points by Texas Woman's broke the NCAA record for most points by the losing team. The 112 points the two teams scored in the overtimes also was an NCAA …
Laura Kurz had 21 points and 11 rebounds and Villanova beat No. 20 Notre Dame 58-47 Sunday in the quarterfinals of the Big East tournament.
Lisa Karcic added 11 points for the Wildcats (19-12), whose victory over the Irish in the regular season earned them the fourth seed in the tournament.
Melissa Lechlitner and Ashley Barlow each had 10 for fifth-seeded Notre Dame (22-8).
Villanova hit just two of its first 14 shots and trailed by four at halftime, but opened the second half with an 18-8 run.
"Basically the coach became un-brain dead and started posting (Kurz) up," said Villanova coach Harry Perretta, who shared the conferences coach of the year honors with UConn's Geno Auriemma.
Consecutive 3-pointers from Heather Scanlon gave Villanova a 39-33 lead with 13 minutes left, and Kurz's first 3 put her team up 50-41 with just over 3 minutes left.
"I missed my first five or six shots, but I knew I had to keep shooting," Kurz said. "I try to keep a short-term memory and I always think that my next shot is going in."
The Wildcats were 10 of 25 from 3-point range. Notre Dame attempted just five 3-pointers and made one.
Villanova will be making its 12th appearance in the semifinals. The Wildcats have won the tournament three times, the last in 2003.
The Irish jumped out to an 15-5 lead, but the Wildcats kept in close by going inside to Kurz, who had eight first-half points. Her kickout to Siobhan O'Connor for a 3-pointer cut the lead to 23-21 with 16 seconds left in the first half. But Lechlitner hit an 18-foot jump shot at the halftime buzzer to give the Irish a 25-21 lead.
"With Kurz on the block, we tried some different things with double teaming her," said Lechlitner. "She's a great passer and would find the open shooter and when she didn't she would just drive."
Villanova and Notre Dame each went 10-6 in the Big East this season. The Wildcats came in unranked, but were seeded higher than Notre Dame because they beat the Fighting Irish 55-48 in January.
Perretta said he believes the win should secure and NCAA berth for the Wildcats, who will play either South Florida and top-ranked Connecticut in the semifinals.
"My personal feeling is that we kind of like got that weight off our shoulders and will just show up and play," Perretta said.
ABSTRACT
The molecular basis of the activation of G-proteins by the G-protein coupled receptor for parathyroid hormone (PTH) is unknown. Employing a combination of NMR methods and computer-based structural refinement, structural features involved in the activation of Gα^sub s^ by the PTH receptor (PTH1R) have been determined. Focusing on the C-terminus of the third intracellular loop (IC3), previously shown to be important for Gα^sub s^ activation by PTH1R, the structure of this region, PTH1R(402-408), while bound to Gα^sub s^, was determined by transferred nuclear Overhauser effect spectroscopy. The relative topological orientation of the IC3 while associated with Gα^sub s^ was determined by saturation transfer difference spectroscopy. These experimental data were incorporated into molecular dynamics simulations of the PTH1R and Gα^sub s^ to provide atomic insight into the receptor-protein interactions important for PTH signaling and a structural framework to analyze previous mutagenesis studies of Gα^sub s^. These data provide the first step toward development of a molecular mechanism for the signaling profile of PTH1R, an important regulator of calcium levels in the bloodstream.
INTRODUCTION
Parathyroid hormone (PTH) is a major regulator of blood calcium levels and bone homeostasis (1,2). The hormone acts by way of the PTH/PTHrP receptor (PTH1R), a G-coupled-protein receptor (GPCR), associated with both cyclic adenosine-monophosphate (cAMP) and inositol triphosphate/intracellular calcium signaling pathways (2-5), associated with the activation of Gα^sub s^ and Gα^sub q^, respectively. The basis of the specificity of PTH1R for G-proteins, which structurally are similar (6-8), is not fully understood.
The C-terminus of the α-subunits of G-proteins (Gα) has been established as crucial in the interaction between Gα^sub s^ and GPCRs. Receptor-mediated accumulation of cAMP is blocked by peptide-specific antibodies that bind to the 10 most distal carboxy terminal residues (9,10). In addition, experimentally and genetically generated mutations located in this region of Gα^sub s^ uncouple the G-protein from the receptor (11). Specifically, the C-terminal mutation R385H (12) and R389P (13,14) lead to uncoupling of Gα^sub s^ from all GPCRs, and the deletion of Ile-382 specifically uncouples Gα^sub s^ from PTH1R (16). (For clarity in the description of the interaction between the receptor and G-protein, residues are denoted by the three-letter code and single-letter code for PTH1R and G-protein, respectively.) The deletion of Ile-382 possibly causes a destabilization of the contact between the α5 helix and the α4-β6 loop of Gα^sub s^ by altering the kink located in the middle of the α5 helix (16). The specific uncoupling of Gα^sub s^ indicates the importance of the relative orientations of these secondary structural domains in the interaction between Gα^sub s^ and PTH1R.
Although the significance of the C-terminus of G-proteins in contacting GPCRs has been demonstrated in previous studies, receptor specificity is not dictated by the C-terminus alone. In chimeric studies, the ability of a Gα carboxy terminus to confer receptor specificity on the Gα chimera depends on the receptor with which it is paired (17,18). For example, replacing the five C-terminal amino acid residues of Gα^sub q^ with those of Gα^sub s^ produced a Gα^sub q^ chimera that was able to stimulate phospholipase C in the α^sub s^-coupled V2 vasopressin receptor but not the uncoupled β^sub 2^-adrenergic receptor (17). Also, chimeric Gα^sub s^ protein with the five C-terminal residues replaced with those of Gα^sub q^ was able to stimulate adenylate cyclase in the α^sub q^-coupled bombesin and V1a vasopressin receptors but not the α^sub q^-coupled oxytocin receptor (17). Therefore, additional, unidentified residues of Gα^sub s^ are likely to contact the receptor (19). Evolutionary trace analysis, a method that uses evolutionary conserved residues to predict binding surfaces of proteins that are similar in structure but differ in function, indicates that the receptor binding site of Gα^sub s^ (20) involves the sixth β-strand β6, the N-terminal ends of β4 and β5, and the C-terminus. Studies in which mutations of the solvent exposed residues R280, T284 and I285 in the α3-β5 loop of Gα^sub s^ decreased the β^sub 2^-adrenergic receptor-mediated accumulation of cAMP without affecting guanine nucleotide binding or hydrolysis (19) support the possibility of the N-terminal end of β5 conacting the receptor.
The significance of the N- and C-terminal 8-15 residues of the third intracellular loop (IC3) of GPCRs in coupling to G-protein has been established (21). For PTH1R, the deletion of the 5 C-terminal amino acids produced a 97% reduction in cAMP, but retained 50% of its ability to increase IPs (22), indicating the importance of the C-terminus of IC3 in Gα^sub s^. To provide molecular insight into this interaction, we have undertaken the structural characterization of PTH1R(402-408), containing the important residues previously identified while coupled to Gα^sub s^. Previously we have determined the structure of the IC3 of PTH1R whereas free both in aqueous solution and associated with a membrane environment (23,24), demonstrating structural features at both the N- and C-termini of the IC3. These results clearly illustrate the hydrophobic residues of PTH1R(402-408) are in close contact to Gα^sub s^, and in particular to those residues previously implicated in Gα^sub s^ activation.
METHODS
Construction of Gα^sub s^ expression vector
The cDNA of Gα^sub s^ long was obtained from the UMR cDNA resource center. Standard PCR methods were used to clone the coding sequence of Gα^sub s^ with a 5' Nco1 restriction site and a 3' Xh01 restriction site. The PCR product was digested and ligated into the pCal-n-EK vector (Stratagene, La Jolla, CA). Sequencing of the plasmid using the T7 promoter primer was performed by Agencourt (Beverly, MA).
Expression and purification of Gα^sub s^
Escherichia coli strain BL21 Star(TM) (DE3), transformed with the sequenced plasmid, was used to inoculate 50 mL of LB Broth. The culture was grown overnight at 37�C and was then used to inoculate 2.5 L of LB broth. At OD^sub 600^ = .60, the culture was induced with 2.5 mL of 1M IPTG. The culture was grown for 16 h at 18�C. E. coli was harvested by centrifugal ion at 6.000 rpm for 30 min at 4�C. Cell pellets were resuspended in 50 mM Tris-HCl (pH = 8.0), 150 mM NaCl, 2 mM DTT, 1.0 mM magnesium acetate, 1.0 mM imidazole, 2 mM CaCl^sub 2^. French pressure cell press was used to lyse the cells at 11,000 psi. The lysate was centrifuged at 12,000 rpm for 30 min at 4�C. The supernatant was incubated with 2 mL bed volume of calmodulin affinity resin (Stratagene) on a rotisserie for 5 h at 4�C. The beads were washed with lysis buffer and high salt lysis buffer (300 mM NaCl). The elution buffer (50 mM Tris-HCl (pH = 8.0), 2 mM DTT, 2 mM EGTA, 1 M NaCl) was used to elute Gα^sub s^ from the column in eight 1.5 mL fractions. A sample of each fraction was run on a 10% NuPAGE(TM) Bis-Tris gel (Invitrogen, Carlsbad, CA) with MOPS running buffer (Invitrogen). The fractions were combined and concentrated to 500 �L using Vivaspin4 concentrator (Vivascience) with a 5000 MWCO, PES membrane. The protein was dialyzed into 20 mM Na^sub 2^HPO^sub 4^, 2 mM DTT, pH = 7 using a 500 �L Float-a-lyzer with a 500 MWCO, cellulose ester membrane (Spectrum, Edgewood, NY).
Nuclear magnetic resonance
Transferred NOEs experiments (25-27) were performed on a mixture of 70 �M Gα^sub s^ and 1 mM PTH1R(402-408), a peptide composed of the seven C-terminal residues, Glu-Tyr-Arg-Lys-Leu-Leu-Lys, of IC3 of PTH1R in 20 mM phosphale buffer, pH 7.0, containing 2 mM deuterated DTT and TSP as an internal chemical shift reference. The NMR experiments were performed on a Bruker Avance spectrometer with proton resonance frequency of 600.1 MHz. The peptide is in fast exchange, between the hound and the free state producing large, negative NOEs, indicating association with Gα^sub s^. NMR experiments followed previously published procedures (28). The peaks of the acquired trNOESY experiments, with different mixing times from 50 to 300 ms, were assigned and integrated. Distance geometry calculations, which used constraints generated from holonomic distance bounds and the distances generated by the NOEs, were performed to determine initial structures used for further refinement following methods previously described (28). Saturation-transfer-difference (STD) NMR experiments were carried out with similar sample conditions as the trNOEs, by selective saturation of the Gα^sub s^ and subtraction of spectra without saturation. In the one-dimensional STD experiment the on-resonance selective irradiation of the GSα protein (employing a 50-ms long Gauss-shaped pulse separated by a 1-ms delay) was applied at -0.3 ppm. For the reference spectrum, off-resonance irradiation was applied at 30 ppm. Subtraction of the one-dimensional STD spectra was performed internally via phase cycling after every scan. The spectral width for all one-dimensional STD experiments was 16 ppm. All spectra were recorded with T1ρ filter to eliminate the background protein resonances. The total number of scans was 48 with relaxation delay of 5 s. The water suppression was achieved with WATERGATE scheme.
Molecular modeling
The model of the PTH1R(402-408) peptide hound to Gα^sub s^ protein, was constructed using the bound peptide conformation, as determined by TRNOEs, and the crystal structure of Gα^sub s^ (33). The relative orientation of the peptide with respect to G-protein was defined by STD NMR data. In addition, previous mutational studies, alanine scanning, and evolutionally trace analyses have provided a good description of a tentative binding pocket on Gα^sub s^.
This pocket was sampled with 20 starting conformations of PTH1R(402-408)/Gα^sub s^, and most energetically stable has been chosen for extensive MD simulations, performed with the GROMACS 3.3 software package (29,30), using a simulation cell containing 75,170 water molecules. All atoms were treated in the OPLS-AA (optimized potentials for liquid simulations-all-atom) force field. The complete system was energy-minimized using a steepest descent algorithm. The MD simulation at 300 K (with 0.02 ps temperature bath coupling) was performed for 1 ns. During the simulation the integration time step was 1 fs, and the applied constant pressure was 1 bar. All simulations were performed on Pentium III processors running Linux.
RESULTS
Gα^sub s^ bound structure of PTH1R(402-408)
The peptide is in last exchange between the bound and the free state. The large negative NOEs observed in the trNOE spectrum verity that PTH1R(402-408) weakly binds Gα^sub s^, as anticipated from our previous investigations (28). The seven amino acid C-terminus of IC3 adopts an α-helix structure while bound to Gα^sub s^. The helix is amphipathic, with a well-defined hydrophilic face, expected to interact with solvent, and a hydrophobic face, expected to contact protein.
Saturation transfer difference spectroscopy
In the STD NMR experiment (31,32), Gα^sub s^ is saturated with a selective saturation pulse. PTH1R(402-408), which is in exchange between the bound and the free form, becomes saturated when the peptide is bound to Gα^sub s^. A difference spectrum is generated from subtracting the spectrum with protein saturation from the spectrum without protein saturation. The difference spectrum provides only the signals of the ligand residues most closely associated with the protein. The STD spectrum displays two peaks in the upfield aliphatic region at ~0.70 ppm and 0.76 ppm. These peaks were assigned as the methyl groups of Leu-406 and Leu-407 in the trNOESY spectrum (Fig. 1). Two peaks in the aromatic region of the STD spectrum at 6.6 ppm and 6.8 ppm were assigned as the δ- and ε-carbons of Tyr-403 in the trNOESY spectrum (Fig. 1). The remaining peaks in the aliphatic region of the STD spectrum are located in overlapping β- and γ-carbon regions of the assigned trNOESY spectrum, so a definitive assignment of these peaks cannot he made. However, the peaks are likely to be the β-carbon of Leu-407, the β- or β-carbon of Leu-406, and the γ-carbon of Lys-408 at 1.53 ppm, 1.40 ppm, and 1.26 ppm, respectively. The STD data supports the hypothesis that the hydrophobic lace of PTH1R(402-408), composed of Tyr-403, Leu-406, and Leu-407, contacts Gα^sub s^ and that the hydrophilic face is exposed to solvent.
Model of PTH1R(402-408) in binding pocket of Gα^sub s^
The crystal structure of Gα^sub s^ in complex with GTPγS (33) was used as a starting point for the molecular dynamics simulations. The crystal structure supports previous evidence from both alanine scanning and evolutionary trace analysis that the carboxy terminus, as well as the α4-β6 loop and the α5 helix, form the receptor contact site. The kink in the α5 helix places the carboxy terminus of the α5 helix in close contact to the α4-β6 loop. This positioning is stabilized by the side chain of M386 extending into the hydrophobic pocket created by the amino terminal residues of β5 and β6 (33). The surface created by the α5 helix and the α4-β6 loop is the predicted receptor contact site. The STD data orients the side chains of Tyr-403, Leu-406, and Leu-407 facing Gα^sub s^. Simulations were performed on twenty initial conformations of the PTH1R(402-408) in complex with Gα^sub s^ to sample the tentative binding pocket. The most energetically stable complex was chosen for a longer molecular dynamics run. After 580 ps the hydrophitic side chains of Gln-402, Arg-404, Lys-405, Lys-408 residues remained solvent exposed and the hydrophobic Tyr-403, Leu-406, and Leu-407 residues were positioned in close proximity to Gα^sub s^ residues (Fig. 2). The model of PTH1R(402-408) and Gα^sub s^ after 580 ps of molecular dynamics is shown in Fig. 3. The hydroxyl of Tyr-403 is within hydrogen bonding distance from the hydroxyls of Y360 and S286, 2.6 [Angstrom] and 2.8 [Angstrom], respectively. The δ- and ε-carbons of Tyr-403 are ~5 [Angstrom] from Y358 with the two aromatic rings adopting a T-shaped orientation. Tyr-403 sits in the hydrophobic pocket of Gα^sub s^ ~4.5 [Angstrom] above M386. The δC1 of Leu-406 is 3.8 [Angstrom] from the side chain of R356, and the δC2 of Leu-406 is 4.5 [Angstrom] from the backbone of R356, The δC1 of Leu-407 is 3.8 [Angstrom] from the methyl of M386 and 3.6 [Angstrom] and 4.0 [Angstrom] from the β- and γ-carbons, respectively, of the side chain of Q390. The δC2 of Leu-407 is 3.6 [Angstrom] from the β-carbon of T284. The β-carbon of Leu-407 is 4.8 [Angstrom] from R389. Q390 contributes to the stabilization of the interaction between the α5 helix and the α4-β6 loop by extending into the hydrophobic pocket above M386.
DISCUSSION
The C-terminal portion of the IC3 of the PTH1R has previously been identified as important tor the signaling, and more importantly the G-protein specificity of the receptor. For the PTH receptor, Segre and co-workers have identified a number of important sites for Gα^sub s^ activation (22), similar findings have been reported for a number of GPCRs using different mutagenic approaches, including insertion (21), and loss- (34-36) and gain-of-function (37-39). Here we have employed NMR methods to determine the structure and topological orientation of the C-terminus of IC3 of PTH1R while hound to Gα^sub s^. The results indicate a well-defined amphiphilic α-helix with the hydrophobic face, including Tyr-403, Leu-406, and Leu-407, interacting with the protein.
The mode of interaction between the receptor and G-protein was refined by extensive, solvated MD simulations, providing a structural framework for the analysis of experimental and naturally occurring mutational data from previous studies. The ten most distal C-terminal amino acids of Gα^sub s^ are crucial to forming the stable receptor binding site of Gα^sub s^. M386 reaches into the hydrophobic pocket formed by the N-terminal residues of β5 and β6 (33). Q390 is also extended into this hydrophobic pocket (Fig. 3 B). These residues stabilize the interaction between the α5 helix and the α4-β6 loop. The uncoupling of receptors due to the Gα^sub s^ genetic mutants ΔI382, R385H, and R389P can be explained by the model. I382 does not directly contact the peptide; however, deletion of mis residue would disturb the essential orientation of the 10 most distal C-terminal residues in the α5 helix interacting with the α4-β6 loop and therefore disrupt the hydrophobic pocket of Gα^sub s^. The bulky imidazole ring of histidine in the R385H mutant would block the binding pocket so that the tyrosine residue of PTH1R(402-408) is prevented from entering the pocket and forming important contacts with Gα^sub s^. In addition, the positively charged guanidine group of the extended side chain of R385 is 2.7 [Angstrom] from the negatively charged carboxy side chain of D381. The charge-charge interaction likely stabilizes the structure of the α5 helix. We can hypothesize that the R389P mutation causes a kink in the C-terminus away from the α4-β6 loop so that the orientation of the side chain of the key residue Q390 is altered. Furthermore, the β-carbon of Leu-407 is 4.8 [Angstrom] from the β-carbon of R389. This hydrophnbic contact contributes to the interaction between PTH1R(402-408) and Gα^sub s^. Experimental mutational data suggest that the α3-β5 loop of Gα^sub s^ is important for the receptor-mediated increase in production of cAMP. In the model, δC2 of Leu-407 is <4 [Angstrom] from the β-methyl of T284, which is located in the α3-β5 loop, This hydrophobic interaction contributes to the removal of the highly hvdrophobic leucine from solvent.
The PTH1R/Gα^sub s^ model developed here is in accord with previous studies in addition to providing several previously unidentified residues making significant contributions in the receptor protein interaction. Tyr-403 is buried in the hydrophobic groove of Gα^sub s^, forming hydrogen bonds with both Y360 and S286. Furthermore, Tyr-403 and Y358 are in a t-shaped position, providing additional stabilization of Tyr-403 by aromatic-aromatic interactions. R356, located in the α^sub 4^-β6 loop, is in close proximity to Leu-406. The side chain of R356 extends outward so that the terminal amine groups contact solvent, and the remainder of the side chain shields δC1 of Leu-406 from solvent. Furthermore, the backbone of R356 is 4.5 [Angstrom] from δC2 of Leu-406. The model predicts that mutating residues Y360, S286, Y358, and R356 will disturb the association of Gα^sub s^ to PTH1R and thus lead to a reduction of receptor-mediated accumulation of cAMP.
PTH1R(402-408) inserts the hvdrophobic residues Tyr-403, Leu-406, and Leu-407 in to a hydrophobic groove formed by several secondary structural elements of Gα^sub s^ (Fig. 4). The hydrophobic pocket is mainly formed from the C-terminal to helix, the α4-β6 loop and β6. In addition, residues T284 and S286 from the α3-β5 loop and β5, respectively, contribute to the back of the pocket. The transient and reversible interaction between Gα^sub s^ and PTH1R is largely driven by the nonpolar groups of the receptor interacting with the hydrophobic groove of Gα^sub s^. Strong charge-charge interactions between Gα^sub s^ and PTH1R that would lead to a tight association are avoided, consistent with the general model of G-protein activation and signaling pathways.
Incorporating the IC3 domain into the entire seven-transmembrane, PTH receptor provides the overall topology of the interaction of Gα^sub s^ with PTH1R. The portion of PTH1R that contacts Gα^sub s^ is adjacent to transmembrane helix six and continues the α-helical structure of TM6. Just N-terminal of this region, there is a flexible portion of the IC3 loop, as previously determined by high-resolution NMR (23). The superposition of PTH1R(402-408) onto the corresponding residues of the full structure of PTH1R does not lead to any steric clashes or overlap with the x-ray structure of Gα^sub s^. In Fig. 5, the solvent exposed groove of Gα^sub s^ fits tightly against the helix-loop-helix surface of IC3. Additionally, the hydrophobic residues of PTH1R(402-408) face the hydrophobic pocket of Gα^sub s^. The model proposed here, of the interaction of PTH1R with Gα^sub s^ provides for insight into the intricate, highly specific signaling profile of PTH1R. Future studies will utilize the proposed structural framework to aid in the elucidation of the specificity of PTH1R coupling to Gα^sub s^ and Gα^sub q^.
The authors thank Dr. Maria Pellegrini, Biogen-Idec, for assistance with the NMR experiments.
The research was supported, in part, by the National Institutes of Health through GM-54082.
[Reference]
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[Author Affiliation]
Jessica Plati,* Natia Tsomaia,[dagger] Andrea Piserchio,[dagger] and Dale F. Mierke*[dagger]
* Department of Chemistry, and [dagger] Department of Molecular Pharmacology, Division of Biology & Medicine. Brown University, Providence, Rhode Island
[Author Affiliation]
Submitted August 4, 2006, and accepted for publication September 12, 2006.
Address reprint requests to Dale F. Mierke, Dept. of Molecular Pharmacology, Div. of Biology & Medicine, Box G-B4, Brown University, Providence, RI 02912. Tel.: 401-863-2139; Fax: 401-863-1595; E-mail: dale_mierke@brown.edu.
Andrea Piserchio's present address is New York Structural Biology Center, 89 Convent Ave., New York, New York, 10027.
� 2007 by the Biophysical Society
0006-3495/07/01/535/06 $2.00
doi: 10.1529/biophysj.106.094813
SYCAMORE, Ill. (AP) — A Seattle man pleaded not guilty Thursday in the 1957 kidnapping and killing of a 7-year-old Illinois girl whose body was exhumed this summer by authorities seeking evidence in the case.
Jack McCullough, 71, appeared via a video feed from the DeKalb County Jail to enter his plea in the more than 50-year-old death of Maria Ridulph of Sycamore. Judge Robbin Stuckert also granted the prosecution's request to test McCullough's DNA against evidence recovered from the girl's body.
McCullough responded "Yes, your honor," when the judge asked if he understood that he faces a sentence of life in prison. A grand jury in August indicted McCullough — who went by the name John Tessier when he lived in Sycamore — on felony murder, kidnapping and abduction charges.
McCullough was arrested in Seattle on July 1 and brought to Illinois on July 27 to face charges in one of the oldest cold-case murders in the nation to be reopened. He's being held on $3 million bail.
Maria was abducted as she played outside her home in December 1957. Her body was found the following spring in a wooded area about 120 miles away. Her case made national headlines, and President Dwight Eisenhower and FBI Director J. Edgar Hoover reportedly requested daily updates on the massive search for her.
In a July 7 jailhouse interview with The Associated Press, McCullough said he didn't kill the girl and maintained the same alibi he gave when first questioned by investigators when he was 18: that he could not have committed the murder because he had traveled to Chicago that day for military medical exams before enlisting in the Air Force.
His next court date is Sept. 22.
After a nearly $100 million buy-out, Lancaster-based Kerr Group Inc. has reshuffled its top brass.
Richard Hofmann has replaced D. Gordon Strickland as president and CEO. Lawrence Caldwell has replaced Geoffrey Whynot as vice president and CFO.
Prior to taking the helm at Kerr, Hofmann and Caldwell were with New Canaan Investments Inc. of New Canaan, Conn., Hofmann said.
Strickland and Whynot both left the company. And former senior vice president of sales, Robert S. Reeves, retired after the buy-out, according to Hofmann.
New Canaan Investments is associated with Fremont Partners of San Francisco, which purchased the ailing Kerr group in July for almost $100 million, according to Hofmann.
"After all the changes which took place, things are starting to settle down here," said Hofmann, adding the company has "no specific plans for further changes."
Kerr's private investors have bought back 93 percent of its stock. They hope to turn the once publicly held company into a private one by the end of the year, Hofmann said.
"We're planning to acquire a few other businesses," he added. Kerr, a manufacturer of plastic bottles and lids, is looking at similar companies "around the world and in the East (Coast).
"We think we have a great company here," Hofmann said. "The company was having some financial difficulties, but we think we've ken care of them."
Prior to the buy-out, Ken. had been in the red for almost two years, struggling with a debt burden equal to almost half its annual revenues.
Last year, the company suspended its dividend after losing $12.8 million during the first quarter--$4 million from its normal operations and another $7.5 million in restructuring costs.
It then sold off its home-canning-supply operations. laid off some top brass, closed a California plant and moved its headquarters from California to Lancaster.
After the shuffle, Kerr was $50.9 million in debt. In September 19961 a group of undisclosed investors proposed to purchase the debt with aspirations of acquiring the company in a debt-for-stock swap. But negotiations for the swap broke down earlier this year.
At the time of the buy-out, former president Strickland said the company's board had been debating over "two different paths for the company"--whether to refinance or sell the company.
Hofmann said Fremont has refinanced the debt.
In 1996, Kerr lost $23.1 million of $107 million in revenues.
The company has a total of 900 employees and five manufacturing facilities in Ahoskie, N.C.; Bowling Green, Ky.; two in Jackson. Tenn.; and one in Lancaster with 290 employees.
NEW YORK Long-distance phone companies for years have tried tolure customers with such bonuses as a month of free calling,discounted rates or gift certificates.
But in a move sure to escalate the battle, AT&T is sending $100checks to selected former customers that they may cash if they agreeto switch their service back.
Sprint and MCI criticized the promotion by their much largerrival.
"We view what AT&T's doing as a rather desperate move to buycustomers," said Sprint Corp. spokeswoman Robin Pence.
"They have lost market share," said Debra Shriver, a spokeswomanfor MCI Communications Corp. "They can afford to try to buy it backin a very high-cost way."
AT&T, which has about two-thirds of the long-distance market,won't say how many $100 checks it has sent out, or how it decideswhich former customers get them. Spokesman Mark Siegel said the $100offer is an experiment.
But AT&T also has been sending checks for up to $50 as part of abroader, non-experimental plan.
It's a merry, magical, mirthful excursion though the portals of your mind and the soul of the season. It's an adventure chockful of Christmas goodies and ditties, ranging from Bing Crosby ("White Christmas") and Frank Sinatra singing jazz-tinged Yuletide songs to offerings from Nat "King" Cole (The Christmas Song") to the Latinflavored "Felice Navidad," (I Want to Wish You A Merry Christmas"), to traditional holiday favorite ("Jingle Bells," etc.) -- and refreshing peppermint candy canes.
It's the elf- and Santa Claus-infested CTA Holiday Train.
And it's coming soon, to a neighborhood near you.
After a particularly stressful day at work, at play or with holiday shopping, we, and the CTA, invite you to board the Holiday Train, a delightful and entertaining way to wind down and immerse yourself in the mood of the season, with the polite and attentive workers on the special line.
It'll lift your mood and make your day.
Catch the fever with the Holiday Train through Dec. 22 (It will circle the outer Loop in a continuous circle this Friday from 4 p.m.-5:45 p.m., coinciding with the city Christmas tree lighting in Daley Plaza).
Other times, dates and lines for the Holiday Train can be attained by calling 836-7000 (any area code) and speaking to a customer service representative.
It's an extraordinary and uplifting experience you ought not miss.
Good cheer.
Wednesday night's game between the Greensboro Grasshoppers andWest Virginia Power turned out to be the type of game you hate tosee either team lose.
It was also the type of game that area baseball fans didn't wantto see.
Fortunately for the couple of hundred fans that walked throughthe gates at Appalachian Power Park, they were rewarded with a well-played, and especially well-pitched game.
Even more rewarding was the manner in which the Power escapedwith a 1-0 win that helped the Power (16-23 second half, 51-56)climb out of the cellar in the South Atlantic League's NorthernDivision standings.
The loss dropped Greensboro to 18-21 and 58-51.
After being handcuffed by red-hot Greensboro starter Robert Moreyfor seven innings, the Power took advantage of the Grasshoppers'only pitching change of the evening when third baseman Eric Avilahit the first offering from reliever Miguel Mejia off the lower leftsection of the scoreboard in left-center field.
"I went up there looking for that pitch, in that spot of thezone," Avila said through the translation of Power center fielderMel Rojas, Jr. "I was ready to hit it if it was a strike and hethrew a fastball for a strike."
Morey's seven shutout innings ran his consecutive inningsscoreless streak to 16, following a complete-game shutout in hislast outing.
"I've seen him quite a bit, particularly in college, and the factthat he's hot and throwing up these zeros does not surprise me,"said Power pitching coach Dave Turgeon of Morey, who entered thegame with a 6-7 record and a 6.06 ERA.
"I've seen him and he's much better than the numbers he's put upthis summer."
As Morey frustrated West Virginia hitters, Power starter EliecerNavarro returned the favor against overmatched Greensboro hitters.
Navarro went five innings, allowing five hits, collecting eightstrikeouts, and walking just one.
Reliever Colton Cain (6-7) took over in the sixth and tossed fourinnings to pick up the win.
"I'm very satisfied," said Turgeon of his pitchers' performances."Both threw a lot of strikes and both did it different ways.
"Navarro was more of a frontward, backward kind of guy, movingthe ball around and changing speeds. There was nothing really fancyabout what Cain did. He came in and pounded the zone with old-fashioned fastballs down, and then he mixed in a few soft pitches tokeep them honest."
West Virginia threatened to end Morey's scoreless streak in thefirst inning when leadoff man Drew Maggi doubled down the left fieldline, only to be stranded by a pair of infield pop outs and aninning ending strike out.
The Power never really threatened again until the seven, when DanGrovatt extended his hitting streak to eight games with a one outsingle. Grovatt moved to third when Chase Lyles doubled to left,setting the Power up with two runners in scoring position and withjust one out.
The inning came to a bizarre end one batter later when KevinMort's grounder to drawn in third baseman Joe Bonnadonna, caughtGrovatt in a rundown between third and home.
After retrieving to third, Grovatt was tagged by catcher JacobRealmuto as he stood on third, along with Lyles, who advanced tothird during the rundown.
By rule, Lyles was out when Grovatt was tagged, but having feltthe tag, Grovatt believed he was out.
When Grovatt left the bag and headed to the dugout, via the thirdbase line, he was tagged out by Morey to end the inning.
Lyles led the Power with a pair of hits, while Avila, Maggi,Grovatt, Rojas and Andy Vasquez finished with one hit apiece.
For Greensboro, Noah Perio, Marcell Ozuna and Rand Smith finishedwith two hits apiece.
The two teams finish a four-game series this evening at 7:05 p.m.Left-hander Zac Fuesser (2-4, 3.14 ERA) will take the mound for thePower against Greensboro's Rett Varner (5-5, 5.82).
BOB WOJCIESZAK/DAILY MAIL The West Virginia Powers Dan Grovatt(22) and Chase Lyles are out at third base after Grovatt broke forhome and Lyles went to third. Grovatt got caught in a run down, wentback to third and Lyles was already on the base, causing bothrunners to be out Wednesday against the Greensboro Grasshoppers atAppalachian Power Park. The Greensboro players are catcher JacobRealmuto, left, and third baseman Joe Bonnadonna.
Contact Michael Dailey at mike.dailey@dailymail.com.
NEW YORK - The United Nations should impose targeted sanctions on the Sudanese government if it continues to attack civilians and humanitarian workers in the Darfur region, a U.S.-based human rights organization said in a new report.
Human Rights Watch accused the international community of failing to take effective action despite increased global attention on the crisis.
"Concerned governments and international institutions should be prepared to strengthen the less-than-robust track record on maintaining pressure on the government of Sudan and other parties to the conflict to meet their obligations under law," said the report released on Wednesday.
More than 200,000 people have been killed and 2.5 million displaced in fighting since 2003, when ethnic African rebels in Darfur took up arms against the Arab-dominated government. The government has been accused of retaliating by recruiting militias who are blamed for the worst atrocities against civilians including beatings, murder and rape. The government denies the accusations.
The 76-page report says the human rights situation in Darfur has "evolved from an armed conflict between rebels and the government into a violent scramble for power and resources."
It accuses both sides to the conflict - the Sudanese government and opposing rebel leaders - of indiscriminate attacks on civilians.
The U.N. Security Council has imposed an arms embargo on Sudan and authorized a 26,000-strong U.N.-African Union peacekeeping force this summer to replace 6,000 AU peacekeepers who have been unable to stem the violence.
The council has also ordered sanctions on four Sudanese accused of rights violations in Darfur, but Human Rights Watch criticized the move because the four are not high-level officials.
"The sanctions they've imposed are inconsequential - they are a joke," said Peter Takirambudde, executive director of the HRW's Africa Division. "They placed travel bans on people who have never even left Sudan and financial penalties on people who don't have external accounts."
Takirambudde praised the United States for imposing unilateral sanctions earlier this year on a list of Sudanese companies suspected of shipping arms to Darfur, as well as on three individuals suspected of being involved in the violence.
The report blames divisions among council members for the lack of action and accuses China, a permanent member of the council and the biggest foreign investor in Sudan, of blocking additional targeted sanctions.
It urges the council to take action if a list of benchmarks are not met by the Sudanese government and other parties, including facilitating the deployment of the new peacekeeping force and increasing humanitarian access to the 4.2 million civilians in need.
"Governments and international institutions should take multilateral and if necessary unilateral measures, such as implementing targeted individual sanctions on people identified by the U.N. Panel of Experts, and on other entities, such as companies, that are contributing to rights abuses in Darfur," said the report.
Takirambudde said he welcomes the high-level meeting hosted by Secretary-General Ban Ki-moon at U.N. headquarters Friday to discuss the deployment of the peacekeeping force, but was skeptical of its outcome. Sanctions are not on the meeting agenda.
"There have been too many meetings, too many summits, consultations. ... This has been an ongoing crisis since 2003 and there is massive suffering continuing, it is pervasive all over Darfur and these people can't wait another day," he said.
On the eve of that meeting, Luis Moreno-Ocampo, the chief prosecutor of the International Criminal Court, urged world leaders to put justice at the top of the agenda because there will be no peace as long as alleged war criminals remain free in Sudan.
Ministers from 26 countries have been invited to attend Friday's meeting aimed at mobilizing international support for new political negotiations, deployment of the AU-U.N. force and expanding humanitarian assistance to Darfur.
Moreno-Ocampo said it should be used to remind the Sudanese government of its duty to arrest the country's humanitarian affairs minister, Ahmed Harun, who is suspected of involvement in the murder, rape, torture and persecution of civilians in Darfur.
---
AP writer Edith M. Lederer at the United Nations contributed to this report.
Netherlands midfielder Nigel de Jong says the country's national team is ready to win the World Cup for the first time.
De Jong, who helped the Netherlands beat Denmark 2-0 Monday, says the squad is ready.
He says "I think we just have to deliver this World Cup. We have got enough quality to do it."
The Netherlands reached the final in 1974 and '78, but lost both times.
KATHERINE D. ARBUTHNOTT, DENNIS W. ARBUTHNOTT and VALERIE A. THOMPSON The Mind in Therapy: Cognitive Science for Practice Mahwah, NJ: Lawrence Erlbaum, 2006, 432 pages (ISBN 0-8058-5675-7, US$49.95 Paperback) Reviewed by DAVIDJ. A. DOZOIS
Cognitive science has undoubtedly contributed importantly to our understanding of adaptive and maladaptive human functioning and will increasingly continue to do so. Basic cognitive science offers a tremendous wealth of knowledge about various processes and mechanisms that are fundamental to a client's functioning, a therapist's efficacy, and the client-therapist interaction. Among other forms of psychological interventions, cognitive therapy has explicitly adopted constructs and adapted methodologies from cognitive science and has evolved conceptually and clinically as a result of this empirical work (cf. Clark & Fairburn, 1997). As McFaIl and Townsend (1998) cogently argued, however, most clinical psychologists focus on idiographic solutions to a client's problems and pay less attention to the nomothetic solutions that pertain to a broader range of issues: "It is as if the two worlds of psychology not only moved in independent orbits, but also occupied different corners of the universe. Many clinical psychologists seem unaware of and unaffected by developments and discoveries in the nomothetic world, even when these potentially could help them understand, assess, treat, predict, and prevent psychopathology and other suffering" (p. 325). Clinical science and practice, they contend, would benefit from greater integration with cognitive science.
In The Mind in Therapy: Cognitive Science for Practice, Arbuthnott, Arbuthnott, and Thompson attempt to bridge this gap by grounding psychotherapy in basic cognitive science. They do not intend to do so in the way that empirically based treatment does (i.e., by demonstrating what works for which particular psychiatric difficulties or by examining what are the effective ingredients of therapy) ; rather, their text applies the conceptual underpinnings of cognitive science, and its empirical findings, to particular practical issues. This book is thus timely, innovative, and interesting.
In 16 chapters, the authors review different areas of cognitive research and emphasize findings relevant to the theoretical and applied aspects of psychotherapy. An overarching objective of the book is to better inform practitioners about some of the key cognitive variables that impact clients, therapists, and the therapy process. Each chapter begins with general definitions of key terms and explains how various cognitive constructs, and the research literature surrounding them, are important to psychotherapy. Many chapters also include case illustrations to translate these concepts into application.
In Chapter 1, the authors make the case that cognitive processes are essential to all forms of psychotherapy in that they provide the pathways for treatment change or set up constraints to psychotherapeutic intervention. In the second chapter, Arbuthnott and her co-authors contextualize the processes and methods of psychotherapy within the framework of problem-solving. They review the literature on what facilitates effective problem-solving and how to overcome deficits and impasses. Chapter 3 provides a good review of memory retrieval and priming. The issue of how past memories are activated is described, vis-�-vis an associated network, and recommendations are made for how therapists might elicit and reframe a client's autobiographical memories in the most effective manner possible. The literature pertaining to autobiographical memory, the "lifeblood of psychotherapy" (p. 55) is further elaborated upon in Chapters 4 and 5. Common errors in autobiographical memory (e.g., overconfidence, schematic knowledge errors) are also described and the implications for therapists highlighted. In Chapter 6, prospective memory is discussed in the context of between-session extratherapy tasks. The authors state that therapists often assume that the failure to complete homework is due to motivational issues when this problem may, instead, be related to prospective memory lapses. Although this is an interesting proposition, it does beg the question of whether particular homework assignments may not be important enough to clients if they need additional cues to trigger memory for task completion. The literature on attentional processes, category judgment, decision-making and reasoning, counterfactual thinking and meta-cognition are then addressed in a series of very interesting, thought-provoking and well-written chapters (Chapters 7-12). The dynamic relationship between cognition and emotion is also described as it pertains to attention, memory, judgment, and emotion regulation (Chapter 13). The benefits and limitations of cognitive and behavioural inhibition are outlined in Chapter 14. Basic cognitive processes are then applied to the understanding of some of the major principles and tenets of psychodynamic therapy (Chapter 15). Although intriguing, the inclusion of this chapter stood out as a bit curious in my opinion. The theme of the book is how cognitive science is relevant to the process of psychotherapy regardless of one's theoretical orientation. Why the authors chose to demonstrate specifically how cognitive science maps on to extant psychodynamic principles is not clear. They argue that "cognitive theory has been of special benefit to psychodynamic theory" (p. 327), the meaning of which is vague (i.e., the authors could be stating either that psychodynamic therapy has benefited most from cognitive science or that this approach has the most to gain by incorporating cognitive science within its theory and practice and establishing a more sophisticated empirical base). If the authors are referring to the latter, they are likely correct; psychodynamic theory would indeed benefit from the refraining of constructs proposed by Arbuthnott et al. in that it would help to separate what is congruent with basic cognitive functioning and what it not. However, the focus on this modality of treatment to the relative exclusion of others is not entirely consistent with the broad approach of the book. Moreover, the vast knowledge base of clinical cognitive science (which has been applied to cognitive therapy and continues to influence its development) is underdeveloped in this text. It would also have been nice to have read some discussion about the use of cognitive methodologies in the assessment of treatment outcome (e.g., Segal, 1997). The final chapter summarizes the literature and attempts to address the question, "So how are therapists to proceed?" Recommendations are provided for how to apply the findings from cognitive science to various stages in therapy (initial session, diagnosis, treatment planning, intervention, and termination). The authors appropriately qualify this chapter, stating that the suggestions they provide are necessarily speculative given that so little integrative work has been conducted in this area. Nonetheless, the recommendations are solidly placed within the framework of basic cognitive processes and are worth considering.
The goal of the book - to increase clinicians' understanding of the cognitive processes and mechanisms involved in therapy and to encourage practitioners to integrate this knowledge within the treatments that they provide - is certainly achieved. A selling feature of this book is that it does start to bridge the gap between cognitive science and clinical practice. Being a scientist-practitioner involves not only paying attention to what works in therapy (i.e., the treatment outcome literature) but also having a firm conceptual and empirical grasp of the mechanisms involved in assessment and treatment. This book facilitates such an understanding. Practitioners who read this text will be more cognizant of the cognitive processes that influence treatment and, rather than having these processes impact therapy in automatic, unintended, and potentially harmful ways, may be more deliberate in their use of cognitive mechanisms in therapy.
[Reference]
References
Clark, D. M., & Fairburn, C. G. (Eds.). (1997). Science and practice of cognitive-behavioural therapy (pp. 119-154). New York: Oxford University Press.
McFall, R. M., & Townsend, J. T. (1998). Foundations of psychological assessment: Implications for cognitive assessment in clinical science. Psychological Assessment, 10, 316-330.
Segal, Z. V. (1997). Implications of priming for measures of change following psychological and pharmacological treatments. In H. H. Strupp, L. M. Horowitz, & M.J. Lambert (Eds.), Measuring patient changes in mood, anxiety, and personality disorders: Toward a core battery (pp. 81-99). Washington, DC: American Psychological Association.
[Author Affiliation]
Katherine D. Arbuthnott is Professor of Psychology at the University of Regina. Her research interests include inhibitory processes in attention, memory, and behavioural control and memory accuracy. Her work has recently been published in the Canadian Journal of Experimental Psychology and Memory & Cognition.
Dennis W. Arbuthnott is a therapist in private practice in Regina. He has written articles published in Thinking & Reasoning, Journal of Memory and Language, and the Canadian Journal of Experimental Psychology,
Valerie A. Thompson is Professor of Psychology at the University of Saskatchewan.
David J. A. Dozois is Associate Professor in the Department of Psychology at the University of Western Ontario. His research focuses on cognitive vulnerability to depression. He also maintains a small private practice.
The British Olympic Association has hired top American public relations executive Darryl Seibel to help raise the profile of its athletes before the 2012 London Games.
Seibel described his new role as head of Britain's Olympic media and communications division on Tuesday as a "once-in-a-generation chance to transform Olympic sport across the country."
He was the chief communications officer for the U.S. Olympic Committee for almost seven years. Seibel left in 2009 and was at the Vancouver Olympics with the BOA in February.
Seibel, who has worked at seven Olympics, will return to sports strategy company 776 Original Marketing after the 2012 games.
"I told them that I thought that in the future that the importance of the nuclear deterrent would grow, rather than diminish, partly because of the nsks of proliferation...To the extent that [the Russians] rely more and more on their nuclear capabilities...it seems to me that it underscores the importance of our sustaining a valid nuclear deterrent, a modern nuclear detenent"
-Secretary of Defense Robert Gates, June 10 speaking to reporters about his speech to Air Force personnel at Scott Air Force Base after earlier firing Air Force leaders for a series of mishaps involving nuclear weapons.
"It sounds paradoxical but there was more mutual trust and respect during the Cold War. Perhaps this was due to there being less lecturing on how one should behave. "
-Russian Foreign Minister Sergey Lavrov, June 20, during remarks in Moscow at an international symposium, "Russia in the 21st Century."
SHANGHAI, China - Chinese stocks rebounded in volatile trading Tuesday following their sharpest one-day drop in three months as strong buying by institutions offset selling by retail investors.
The benchmark Shanghai Composite Index gained 2.6 percent to 3,767.10 after a rollercoaster session that saw the index plunge as much as 7.2 percent earlier in the day. It fell 8.3 percent on Monday - the benchmark's sharpest decline since an 8.8-percent drop Feb. 27 triggered a global market sell-off.
The Shenzhen Composite Index for China's smaller second market rose 2.5 percent to 1,066.05.
Regional market reaction was muted, with Japan's benchmark index climbing 0.5 percent and Hong Kong shares up 0.7 percent by mid-afternoon.
Chinese investors had dumped shares Friday and Monday in reaction to a government decision last week to triple a tax on stock trades, viewing the move as a signal regulators are determined to cool frenzied trading that had lifted stock prices nearly 60 percent since the start of the year, following a 130 percent surge in 2006.
By Tuesday's close, the benchmark Shanghai index was 13 percent below its record high of 4,334.92, hit May 29. But it was still up 40 percent for the year so far.
China's stock markets are largely closed to foreign investors. Analysts attributed the sell-off Monday to panic-selling by individual retail investors.
The stock market boom has prompted millions of first-time investors to jump into the market, tapping savings and retirement accounts and mortgaging homes to buy stocks. Authorities are worried that the new money is fueling a bubble in prices.
Shifting to damage control, on Tuesday state-run newspapers carried prominent articles announcing the approval of four new investment funds.
Financial newspapers sought to reassure investors, asserting that the tax hike on stock trades would help the markets by encouraging longer-term investments in better stocks.
International stock markets have shrugged off the declines in mainland Chinese declines. Most Asian markets rose Monday, and Wall Street also eked out gains.
Economists say the recent fall in Chinese prices should have only a modest impact on the overall economy because China's growth is driven by exports, not the financial markets, and families have still much more money in savings than in shares.
The first students from an innovative new training scheme havegraduated as fully-fledged British Gas service engineers.
RESTON, Virginia (AP) — Cyber Monday was the busiest online shopping day ever with consumers spending an estimated $1.25 billion. That's up 22 percent from the total spent last year on the Monday after Thanksgiving.
Research group comScore said Tuesday that it estimates 10 million people bought things online Monday. The average shopper spent 9 percent more this year, or roughly $125.
Cyber Monday sales topped $1 billion for the first time last year.
Giles introduces substance abuse bill for inmates
Under new legislation, substance abusers who have been convicted of a drug-related offense and are incarcerated-will be mandated to enroll in a treatment program before they can receive good conduct credit, thanks to state Rep. Calvin Giles (D-8th), who said they must take responsibility for their addictions.
"Before a prisoner can begin to accumulate good conduct credit, it is critical they address and take responsibility for their addiction," Giles said, explaining how current law provides that a prisoner who is serving a sentence receives one day of good credit for each day of incarceration and how they may be eligible for additional good conduct credit as the Illinois Department of Corrections (IDOC) deems proper.
Giles' bill would prevent an inmate from receiving good credit until completion of a substance abuse program when the prisoner's crime was committed as a result of alcohol or controlled substance use, abuse or addiction.
Should the inmate complete the program, the Department of Corrections would award good conduct for the time spent in the treatment program.
"This legislation is both correctional and prevention," Giles said. "It mandates that prisoners receive treatment for their addiction while they are institutionalized and equips them with the tools they need to lead a substancefree life following their release from prison."
The House also passed Rep. Karen Yarbrough's (D-Maywood) identification for ex-offenders bill she says is needed to help them gain employment and improve the quality of their lives upon release.
Yarbrough's legislation passed the House State Government Administration Committee and requires the Illinois Department of Corrections (IDOC) to issue ID cards to ex-offenders who are leaving prison. It would also authorize them to exchange the ID cards for standard State of Illinois identification.
"It is unfortunate that those leaving prison are often left without the initial form of identification needed to obtain a Social Security Card, Birth Certificate and other important documentation needed to secure employment," she stated.
Referring to HB-2011, she added, "If enacted, this measure would provide ex-offenders with a solid first step to being a productive member of society."
Article Copyright Sengstacke Enterprises, Inc.
Three people in Idaho and a woman from Longview have beensickened in a multistate outbreak of E. coli that killed one personin Wisconsin, health officials said.
Food and Drug Administration officials believe the cases arelinked to raw, packaged spinach, and the FDA has advised people notto eat it.
In Washington, health officials said Friday that the outbreak ofE. coli had sickened a woman from Longview, who was tested inOregon.
Officials were still investigating and could not say Fridaywhether the spinach was purchased in Washington, said Deanna Mill,spokeswoman for the Washington Department of Health.
In Idaho, three people were sickened, with one hospitalized, saidRoss Mason of the state Department of Health and Welfare. Thatperson has been released, and all the victims are recovering. Theillnesses occurred in Ada, Canyon and Twin Falls counties.
"Although we have identified packaged spinach as the probablesource, no one has yet been able to pinpoint the brand or the storesfrom which it was purchased," said Dr. Christine Hahn, Idaho's stateepidemiologist. "Were now trying to pin down the brand."
Idaho has asked all grocery stores to voluntarily remove freshbagged spinach from their produce shelves.
Spinach brands recalled
Natural Selection Foods has recalled all packages of its freshspinach and any salad with spinach in a blend. The affected packageshave "Best if Used by Dates" of Aug. 17 through Oct. 1. The recalledbrands are:
Bellissima
Cheney Brothers
Coastline
Compliments
Cross Valley
D'Arrigo Brothers
Dole
Earthbound Farm
Emeril
Fresh Point
Green Harvest
Jansal Valley
Mann
Mills Family Farm
Natural Selection Foods
Nature's Basket
O Organic
Premium Fresh
President's Choice
Pride of San Juan
Pro*Act
Pro-Mark
Rave Spinach
Ready Pac
River Ranch
Riverside Farms
Snoboy
Superior
Sysco
Tanimura & Antle
The Farmer's Market
Trader Joe's
E. coli bacteria found in Longview womanThree people in Idaho and a woman from Longview have beensickened in a multistate outbreak of E. coli that killed one personin Wisconsin, health officials said.
Food and Drug Administration officials believe the cases arelinked to raw, packaged spinach, and the FDA has advised people notto eat it.
In Washington, health officials said Friday that the outbreak ofE. coli had sickened a woman from Longview, who was tested inOregon.
Officials were still investigating and could not say Fridaywhether the spinach was purchased in Washington, said Deanna Mill,spokeswoman for the Washington Department of Health.
In Idaho, three people were sickened, with one hospitalized, saidRoss Mason of the state Department of Health and Welfare. Thatperson has been released, and all the victims are recovering. Theillnesses occurred in Ada, Canyon and Twin Falls counties.
"Although we have identified packaged spinach as the probablesource, no one has yet been able to pinpoint the brand or the storesfrom which it was purchased," said Dr. Christine Hahn, Idaho's stateepidemiologist. "Were now trying to pin down the brand."
Idaho has asked all grocery stores to voluntarily remove freshbagged spinach from their produce shelves.
Spinach brands recalled
Natural Selection Foods has recalled all packages of its freshspinach and any salad with spinach in a blend. The affected packageshave "Best if Used by Dates" of Aug. 17 through Oct. 1. The recalledbrands are:
Bellissima
Cheney Brothers
Coastline
Compliments
Cross Valley
D'Arrigo Brothers
Dole
Earthbound Farm
Emeril
Fresh Point
Green Harvest
Jansal Valley
Mann
Mills Family Farm
Natural Selection Foods
Nature's Basket
O Organic
Premium Fresh
President's Choice
Pride of San Juan
Pro*Act
Pro-Mark
Rave Spinach
Ready Pac
River Ranch
Riverside Farms
Snoboy
Superior
Sysco
Tanimura & Antle
The Farmer's Market
Trader Joe's
Shaws deny Jackson namesake ploy
Illinois Sen. William "Bill" Shaw (D-15th) and his identical twin brother, Cook County Board of Review Comm. Robert Shaw Sunday denied running a 68-year-old Robbins resident who has the same name as Rep. Jesse L. Jackson Jr. (D-2nd) for office, but they say they are backing a candidate they hope will defeat the congressman.
Senator Shaw told the Chicago Defender he is running Yvonne Christian-Williams, an attorney, against Rep. Jackson but, in denying charges of ballot confusion by the congressman with the entry of the Robbins candidate in this race, he wants to know who put Rev. Anthony Williams in this race. "Now, that's the question," quipped the senator.
Shaw, who is also mayor of Dolton, said he is backing Christian-Williams because Jackson "is not taking care of business" in his district. He resents Jackson's writing a book and spending more time in Washington than Chicago.
"He doesn't even have an office in Chicago where the people need the help the most and we're tired of him sending this white boy to answer questions. We didn't elect him."
Accustomed to getting and surviving a lot of political heat, the colorful twins, who will turn 65 on July 31st, voiced outrage over the Jackson's anger of having competition in the upcoming congressional race.
While Rep. Jackson said the so-called phantom Jackson didn't exist, the candidate surfaced over the weekend. During his first press conference held over the weekend at the Ramada Hotel, 17400 S. Halsted, Homewood, the Robbins candidate and his attorney, Evangeline Levison, claimed his candidacy is legitimate.
Levison said she is "not aware of the Shaws backing" her client and that the senator is backing another candidate. "I'm not aware of any connection there," she stated.
While ducking questions from reporters, the Robbins candidate simply said: "I exist." "I am here today because there are questions about whether I do exist. Well, I do exist and I'm here in the flesh."
Claiming to be a lifelong resident of Robbins, Jackson said "I expect to win" but neither he nor Levison, who was the attorney that represented then Dixmoor mayoral candidate Donald Luster, an ex-felon who went on to win his race, would give any background on Jackson.
Both the senator and his brother denied knowing the Robbins candidate with the commissioner saying: "People have run against me in every election and I've been able to survive this. Put your record out there against the opponents and people make the judgments. That's what we do in America.
"There have been two Shaws on the ballot for a long time here and we've gotten elected and reelected. I trust the people," the commissioner said. "This is much to do about nothing. There are a lot of Jesse Jacksons...a lot of Robert Shaws. This (Robbins) Jackson had his name longer than" either the congressman or his father, the Rev. Jesse L. Jackson Sr.
"All is fair in love and war," Comm. Shaw quipped.
Shaw told Rep. Jackson to "put his record on the line and stop making bogus allegations and get re-elected, if he can."
Calling Jackson "inept," Shaw said: "We pay him $145,000 a year and he has to write more books to raise him some more personal money... he doesn't care about the people."
Article Copyright Sengstacke Enterprises, Inc.
Photo (William Shaw and Yvonne Christian-Williams)
