The parathyroid hormone receptorsome and the potential for therapeutic intervention.

The parathyroid hormone 1 receptor (PTH1R) is activated by parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP), hormones that mediate mineral ion homeostasis and tissue development, respectively. These diverse actions mediated by one receptor are likely due to the formation of cell-specific receptorsome complexes with cytosolic constituents. Through the second and third intracellular loops, the PTH1R couples to several G protein subclasses, including Gs, Gq/11, Gi/o and G12/13, resulting in the activation of many pathways.

Alkylstrontium diamidoboranes: β-hydride elimination and Sr-C insertion.

Alkylstrontium secondary amidoboranes are shown to undergo β-hydride elimination and Sr-C insertion reactions; observations which provide support for similar processes in d(0)-catalysed dialkylamine borane dehydrocoupling.

Cochlear-implanted children from homes where English is an additional language: findings from a recent audit in one London centre.

A 5-year retrospective audit of demographic, audiological, and other records of 147 children implanted at one London centre was conducted. The aim was to detail the number of children implanted, with a specific focus on children from families with English as an additional language (EAL), and to compare these children with children from monolingual English-speaking families on a variety of characteristics known to affect paediatric cochlear implant outcomes. In all, 28% of children were from families where English is an additional language, with 15 different languages recorded.

Formation and reactivity of the cyclometallated N-heterocyclic carbene complexes [Ru(NHC)'(dppe)(CO)H].

Thermolysis of [Ru(PPh(3))(dppe)(CO)HCl] (dppe = 1,2-bis(diphenylphosphino)ethane) with the N-heterocyclic carbenes I(i)Pr(2)Me(2) (1,3-diisopropyl-4,5-dimethyl-imidazol-2-ylidene), IEt(2)Me(2) (1,3-diethyl-4,5-dimethyl-imidazol-2-ylidene) or ICy (1,3-dicyclohexylimidazol-2-ylidene) gave the cyclometallated carbene complexes [Ru(NHC)'(dppe)(CO)H] (NHC = I(i)Pr(2)Me(2), 4; IEt(2)Me(2), 5; ICy, 6). Dissolution of 4 in CH(2)Cl(2) or CHCl(3) gave the trans-Cl-Ru-P complex [Ru(I(i)Pr(2)Me(2))'(dppe)(CO)Cl] (7), which converted over hours at room temperature to the trans-Cl-Ru-CO isomer 7'. Chloride abstraction from 7 by NaBPh(4) under an atmosphere of H(2) produced the cationic mono-hydride complex [Ru(I(i)Pr(2)Me(2))(dppe)(CO)H][BPh(4)] (9), which could also be formed by protonating 4 with 1 eq HBF(4)·OEt(2).

Ruthenium bidentate phosphine complexes for the coordination and catalytic dehydrogenation of amine- and phosphine-boranes.

Addition of the amine-boranes H(3)B⋅NH(2)tBu, H(3)B⋅NHMe(2) and H(3)B⋅NH(3) to the cationic ruthenium fragment [Ru(xantphos)(PPh(3))(OH(2))H][BAr(F)(4)] (2; xantphos=4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; BAr(F)(4)=[B{3,5-(CF(3))(2)C(6)H(3)}(4)](-)) affords the η(1)-B-H bound amine-borane complexes [Ru(xantphos)(PPh(3))(H(3)B⋅NH(2)tBu)H][BAr(F)(4)] (5), [Ru(xantphos)(PPh(3))(H(3) B⋅NHMe(2))H][BAr(F)(4)] (6) and [Ru(xantphos)(PPh(3))(H(3)B⋅NH(3))H][BAr(F)(4)] (7). The X-ray crystal structures of 5 and 7 have been determined with [BAr(F)(4)] and [BPh(4)] anions, respectively. Treatment of 2 with H(3)B⋅PHPh(2) resulted in quite different behaviour, with cleavage of the B-P interaction taking place to generate the structurally characterised bis-secondary phosphine complex [Ru(xantphos)(PHPh(2))(2)H][BPh(4)] (9).

Apical membrane segregation of phosphatidylinositol-4,5-bisphosphate influences parathyroid hormone 1 receptor compartmental signaling and localization via direct regulation of ezrin in LLC-PK1 cells.

The parathyroid hormone 1 receptor (PTH1R), a primary regulator of mineral ion homeostasis, is expressed on both the apical and basolateral membranes of kidney proximal tubules and in the LLC-PK1 kidney cell line. In LLC-PK1 cells, apical PTH1R subpopulations are far more effective at signaling via phospholipase (PLC) than basolateral counterparts, revealing the presence of compartmental signaling. Apical PTH1R localization is dependent upon direct interactions with ezrin, an actin-membrane cross-linking scaffold protein.

Asymmetric Strecker synthesis of α-arylglycines.

A practically simple three-component Strecker reaction for the asymmetric synthesis of enantiopure α-arylglycines has been developed. Addition of a range of aryl-aldehydes to a solution of sodium cyanide and (S)-1-(4-methoxyphenyl)ethylamine affords highly crystalline (S,S)-α-aminonitriles that are easily obtained in diastereomerically pure form. Heating the resultant (S,S)-α-aminonitriles in 6 M aqueous HCl at reflux resulted in cleavage of their chiral auxiliary fragments and concomitant hydrolysis of their nitrile groups to afford enantiopure (S)-α-arylglycines.

Aromatase and dual aromatase-steroid sulfatase inhibitors from the letrozole and vorozole templates.

Concurrent inhibition of aromatase and steroid sulfatase (STS) may provide a more effective treatment for hormone-dependent breast cancer than monotherapy against individual enzymes, and several dual aromatase-sulfatase inhibitors (DASIs) have been reported. Three aromatase inhibitors with sub-nanomolar potency, better than the benchmark agent letrozole, were designed. To further explore the DASI concept, a new series of letrozole-derived sulfamates and a vorozole-based sulfamate were designed and biologically evaluated in JEG-3 cells to reveal structure-activity relationships.

Stoichiometric reactivity of dialkylamine boranes with alkaline earth silylamides.

Reactions of β-diketiminato group 2 silylamides, [HC{(Me)CN(2,6-(i)Pr(2)C(6)H(3))}(2)M(THF)(n){N(SiMe(3))(2)}] (M = Mg, n = 0; M = Ca, Sr, n = 1), and an equimolar quantity of pyrrolidine borane, (CH(2))(4)NH·BH(3), were found to produce amidoborane derivatives of the form [HC{(Me)CN(2,6-(i)Pr(2)C(6)H(3))}(2)MN(CH(2))(4)·BH(3)]. In reactivity reminiscent of analogous reactions performed with dimethylamine borane, addition of a second equivalent of (CH(2))(4)NH·BH(3) to the Mg derivative induced the formation of a species, [HC{(Me)CN(2,6-(i)Pr(2)C(6)H(3))}(2)Mg{N(CH(2))(4) BH(2)NMe(2)BH(3)}], containing an anion in which two molecules of the amine borane substrate have been coupled together through the elimination of one molecule of H(2). Both this species and a calcium amidoborane derivative have been characterised by X-ray diffraction techniques and the coupled species is proposed as a key intermediate in catalytic amine borane dehydrocoupling, in reactivity dictated by the charge density of the group 2 centre involved.

Silver coordination networks and cages based on a semi-rigid bis(isoxazolyl) ligand.

The semi-rigid ligand 1,4-bis((3,5-dimethylisoxazol-4-yl)methyl)benzene (bisox) reacts with a range of silver(i) salts to give products in which the anions dictate the structure. The reactions with AgNO(3) and AgO(2)CCF(3) both lead to compounds in which the anions are coordinated to the silver centres. Thus, the structure of [Ag(2)(NO(3))(2)(bisox)] 1 contains helical silver-nitrate chains that are linked into sheets by bridging bisox ligands, whereas the structures of [Ag(O(2)CCF(3))(bisox)]·0.

A family history intervention: enhancing cardiovascular risk assessment.

This article describes the effect of individualized counseling using family history data and objective cardiovascular risk factors on intent to change and actual exercise behavior in a diverse sample of working adults. Using a longitudinal, quasi-experimental, crossover design, objective data (blood lipids, glucose, blood pressure, and body mass index) and subjective data (awareness of heart disease risk, depression, spirituality, and knowledge of family history) were collected from 91 (mostly female and with a mean age of 45 years) primary and secondary teachers in a southwestern city. The Transtheoretical Model of Change guided the study and measured intent to exercise.

Nursing and conflict communication: avoidance as preferred strategy.

An exploratory study was conducted to examine nurses' (n = 57) selection of strategies to confront conflict in the workplace. Communication competence is the conceptual framework, defining competent conflict communication as joint problem-solving communication that is both effective and appropriate. Items were drawn from tools assessing nurses' conflict management strategies.

An advance directive in two questions.

It has been two decades since advance directives have become an integral part of health care. Impediments to their optimal usage are common and multifactorial. Decisions commonly have to be made when patients are unable to do so or choose not to participate in decision making, often at the end of life.

When is an imine not an imine? Unusual reactivity of a series of Cu(II) imine-pyridine complexes and their exploitation for the Henry reaction.

In this paper we report the synthesis and solid-state structures for a series of pyridine based Cu(II) complexes and preliminary data for the asymmetric Henry reaction. Interestingly, the solid-state structures indicate the incorporation of an alcohol into one of the imine groups of the ligand, forming a rare α-amino ether group. The complexes have been studied via single crystal X-ray diffraction, EPR spectroscopy and mass spectrometry.

Crystallographic characterisation of Ti(IV) piperazine complexes and their exploitation for the ring opening polymerisation of rac-lactide.

In this paper a series of eight Ti(IV) piperazine based complexes have been prepared and fully characterised in the solid-state by X-ray crystallography and in solution via NMR spectroscopy. In the solid-state either Ti(2)(L)(O(i)Pr)(6) or Ti(2)(L)(2)(O(i)Pr)(4) were observed depending upon the nature of the starting ligand. For complexes with less sterically demanding ligands (1H(2) and 2H(2)) an equilibrium was observed: 2 Ti(2)(L)(O(i)Pr)(6) ⇔ Ti(2)(L)(2)(O(i)Pr)(4) + 2 Ti(O(i)Pr)(4).

Experimental and computational investigation of C-N bond activation in ruthenium N-heterocyclic carbene complexes.

A combination of experimental studies and density functional theory calculations is used to study C-N bond activation in a series of ruthenium N-alkyl-substituted heterocyclic carbene (NHC) complexes. These show that prior C-H activation of the NHC ligand renders the system susceptible to irreversible C-N activation. In the presence of a source of HCl, C-H activated Ru(I(i)Pr(2)Me(2))'(PPh(3))(2)(CO)H (1, I(i)Pr(2)Me(2) = 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene) reacts to give Ru(I(i)PrHMe(2))(PPh(3))(2)(CO)HCl (2, I(i)PrHMe(2) = 1-isopropyl-4,5-dimethylimidazol-2-ylidene) and propene.

Acute down-regulation of sodium-dependent phosphate transporter NPT2a involves predominantly the cAMP/PKA pathway as revealed by signaling-selective parathyroid hormone analogs.

The parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTHR1) in cells of the renal proximal tubule mediates the reduction in membrane expression of the sodium-dependent P(i) co-transporters, NPT2a and NPT2c, and thus suppresses the re-uptake of P(i) from the filtrate. In most cell types, the liganded PTHR1 activates Gα(S)/adenylyl cyclase/cAMP/PKA (cAMP/PKA) and Gα(q/11)/phospholipase C/phosphatidylinositol 1,4,5-trisphosphate (IP(3))/Ca(2+)/PKC (IP(3)/PKC) signaling pathways, but the relative roles of each pathway in mediating renal regulation P(i) transport remain uncertain. We therefore explored the signaling mechanisms involved in PTH-dependent regulation of NPT2a function using potent, long-acting PTH analogs, M-PTH(1-28) (where M = Ala(1,12), Aib(3), Gln(10), Har(11), Trp(14), and Arg(19)) and its position 1-modified variant, Trp(1)-M-PTH(1-28), designed to be phospholipase C-deficient.

Predictors of response to ultrabrief right unilateral electroconvulsive therapy.

Background: Recent trials have demonstrated clinically meaningful efficacy and minimal cognitive side effects with ultrabrief pulsewidth right unilateral (RUL) ECT. In many countries it is gradually being adopted into clinical practice and further information on predictors of response is needed.

Methods: Data collected from 75 depressed patients who received ultrabrief RUL ECT in a prospective research trial were analysed for predictors of response.

Magnesium hydride-promoted dearomatisation of pyridine.

Reaction of pyridine with well defined magnesium hydride species results in heterocycle dearomatisation by a hydride transfer which occurs with the formation of magnesium compounds containing 1,2- and 1,4-dihydropyridide anions as the respective kinetic and thermodynamic products.

Zinc(II) silsesquioxane complexes and their application for the ring-opening polymerization of rac-lactide.

In this Communication, we report the unprecedented solid-state structures for a series of zinc(II) silsesquioxane complexes. Initial catalytic data for the ring-opening polymerization of rac-lactide are also presented together with analogous heterogeneous species.

Potent constitutive cyclic AMP-generating activity of XLαs implicates this imprinted GNAS product in the pathogenesis of McCune-Albright syndrome and fibrous dysplasia of bone.

Patients with McCune-Albright syndrome (MAS), characterized primarily by hyperpigmented skin lesions, precocious puberty, and fibrous dyslasia of bone, carry postzygotic heterozygous mutations of GNAS causing constitutive cAMP signaling. GNAS encodes the α-subunit of the stimulatory G protein (Gsα), as well as a large variant (XLαs) derived from the paternal allele. The mutations causing MAS affect both GNAS products, but whether XLαs, like Gsα, can be involved in the pathogenesis remains unknown.

Clinical decision making in palliative care and end of life care.

Clinical decision making involves a consideration of multiple factors; clinical options are constructed based on the objective clinical data and evidence-based standards. Technologic advances have led not only to life saving interventions, but also to the use of these technologies when benefit to the patient was unclear or unexamined. The cases of Karen Quinlan, Nancy Cruzan, and Terri Schiavo provide a framework for examining the evolution of clinical decision making, including when to use or not to use technologies such as ventilators and artificial nutrition and hydration, and the role of specific questions in the process.