NEO-PI-R Domain and Facet Scale Predictors of Achievement Dispositions

2000 ◽  
Author(s):  
Kelli Canada ◽  
Scott R. Ross ◽  
M. Karega Rausch
Keyword(s):  
R Domain

scholarly journals Analysis of the Genetic Variability of Virulence-Related Loci in Epidemic Clones of Methicillin-Resistant Staphylococcus aureus

2005 ◽  
Vol 49 (1) ◽  
pp. 366-379 ◽  
Author(s):  
A. R. Gomes ◽  
S. Vinga ◽  
M. Zavolan ◽  
H. de Lencastre
Keyword(s):  
Staphylococcus Aureus ◽  
Genetic Variability ◽  
Amino Acid Level ◽  
Point Of View ◽  
Sequence Motifs ◽  
Related Factors ◽  
Specific Sequence ◽  
Methicillin Resistant ◽  
Sequence Types ◽  
R Domain

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) isolates have previously been classified into major epidemic clonal types by pulsed-field gel electrophoresis in combination with multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec typing. We aimed to investigate whether genetic variability in potentially polymorphic domains of virulence-related factors could provide another level of differentiation in a diverse collection of epidemic MRSA clones. The target regions of strains representative of epidemic clones and genetically related methicillin-susceptible S. aureus isolates from the 1960s that were sequenced included the R domains of clfA and clfB; the D, W, and M regions of fnbA and fnbB; and three regions in the agr operon. Sequence variation ranged from very conserved regions, such as those for RNAIII and the agr interpromoter region, to the highly polymorphic R regions of the clf genes. The sequences of the clf R domains could be grouped into six major sequence types on the basis of the sequences in their 3′ regions. Six sequence types were also observed for the fnb sequences at the amino acid level. From an evolutionary point of view, it was interesting that a small DNA stretch at the 3′ clf R-domain sequence and the fnb sequences agreed with the results of MLST for this set of strains. In particular, clfB R-domain sequences, which had a high discriminatory capacity and with which the types distinguished were congruent with those obtained by other molecular typing methods, have potential for use for the typing of S. aureus. Clone- and strain-specific sequence motifs in the clf and fnb genes may represent useful additions to a typing methodology with a DNA array.

scholarly journals Structure and Function of the CFTR Chloride Channel

1999 ◽  
Vol 79 (1) ◽  
pp. S23-S45 ◽  
Author(s):  
DAVID N. SHEPPARD ◽  
MICHAEL J. WELSH
Keyword(s):  
Cystic Fibrosis ◽  
Chloride Channel ◽  
Atp Hydrolysis ◽  
Current Knowledge ◽  
Structure And Function ◽  
Binding Domains ◽  
Transporter Family ◽  
Membrane Spanning ◽  
And Function ◽  
R Domain

Sheppard, David N., and Michael J. Welsh. Structure and Function of the CFTR Chloride Channel. Physiol. Rev. 79 , Suppl.: S23–S45, 1999. — The cystic fibrosis transmembrane conductance regulator (CFTR) is a unique member of the ABC transporter family that forms a novel Cl− channel. It is located predominantly in the apical membrane of epithelia where it mediates transepithelial salt and liquid movement. Dysfunction of CFTR causes the genetic disease cystic fibrosis. The CFTR is composed of five domains: two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory (R) domain. Here we review the structure and function of this unique channel, with a focus on how the various domains contribute to channel function. The MSDs form the channel pore, phosphorylation of the R domain determines channel activity, and ATP hydrolysis by the NBDs controls channel gating. Current knowledge of CFTR structure and function may help us understand better its mechanism of action, its role in electrolyte transport, its dysfunction in cystic fibrosis, and its relationship to other ABC transporters.

scholarly journals Computational Studies Reveal Phosphorylation-dependent Changes in the Unstructured R Domain of CFTR

2008 ◽  
Vol 378 (5) ◽  
pp. 1052-1063 ◽  
Author(s):  
Tamás Hegedűs ◽  
Adrian W.R. Serohijos ◽  
Nikolay V. Dokholyan ◽  
Lihua He ◽  
John R. Riordan
Keyword(s):  
Computational Studies ◽  
R Domain

scholarly journals Simple binding of protein kinase A prior to phosphorylation allows CFTR anion channels to be opened by nucleotides

2020 ◽  
Vol 117 (35) ◽  
pp. 21740-21746
Author(s):  
Csaba Mihályi ◽  
Iordan Iordanov ◽  
Beáta Töröcsik ◽  
László Csanády
Keyword(s):  
Cystic Fibrosis ◽  
Protein Kinase ◽  
Salt Water ◽  
Anion Channel ◽  
Large Network ◽  
Channel Activation ◽  
Incurable Disease ◽  
Cftr Mutations ◽  
In Cells ◽  
R Domain

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) anion channel is essential for epithelial salt–water balance. CFTR mutations cause cystic fibrosis, a lethal incurable disease. In cells CFTR is activated through the cAMP signaling pathway, overstimulation of which during cholera leads to CFTR-mediated intestinal salt–water loss. Channel activation is achieved by phosphorylation of its regulatory (R) domain by cAMP-dependent protein kinase catalytic subunit (PKA). Here we show using two independent approaches––an ATP analog that can drive CFTR channel gating but is unsuitable for phosphotransfer by PKA, and CFTR mutants lacking phosphorylatable serines––that PKA efficiently opens CFTR channels through simple binding, under conditions that preclude phosphorylation. Unlike when phosphorylation happens, CFTR activation by PKA binding is completely reversible. Thus, PKA binding promotes release of the unphosphorylated R domain from its inhibitory position, causing full channel activation, whereas phosphorylation serves only to maintain channel activity beyond termination of the PKA signal. The results suggest two levels of CFTR regulation in cells: irreversible through phosphorylation, and reversible through R-domain binding to PKA––and possibly also to other members of a large network of proteins known to interact with the channel.

scholarly journals Observational connections between LBV’s and other stars, with emphasis on Wolf-Rayet stars

1989 ◽  
Vol 113 ◽  
pp. 229-240
Author(s):  
A. F. J. Moffat ◽  
L. Drissen ◽  
C. Robert
Keyword(s):  
Mass Loss ◽  
Massive Stars ◽  
Underlying Mechanism ◽  
High Mass ◽  
Strong Line ◽  
Essential Step ◽  
High Mass Loss ◽  
Loss Rates ◽  
R Domain

Abstract.We suggest that the LBV mechanism is an essential step to “force” massive stars (M(ZAMS) ≥ 40M⊙) to finally enter the Wolf-Rayet (W-R) domain in the Hertzsprung-Russel diagram (HRD). Just as massive supergiants showincreasingvariability as theyapproachthe Humphreys-Davidson (H-D)instability limit (horizontally in the HRD diagram), so the W-R stars showdecreasingvariability as theyrecede fromthe H-D limit (at first horizontally into the WNL domain, then, with their high mass loss rates, plunging irreversably downwards as ever hotter, smaller and fainter, strong-line W-R stars). Among the W-R stars, the luminous WNL subtypes (especially WN8) are the most variable, probably as a consequence of blob ejection in the wind. The underlying mechanism which triggers this ejection is possibly related to wind instabilities and may thus be quite different from the source of variability in luminous supergiants or LBV’s in quiescence, where photospheric effects dominate.

Efficacy of galcanezumab in patients with chronic migraine and a history of preventive treatment failure

Cephalalgia ◽  
2019 ◽  
Vol 39 (8) ◽  
pp. 931-944 ◽  
Author(s):  
Dustin D Ruff ◽  
Janet H Ford ◽  
Antje Tockhorn-Heidenreich ◽  
Matthew Sexson ◽  
Sriram Govindan ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Migraine Headache ◽  
Medication Use ◽  
Domain Score ◽  
Controlled Study ◽  
Life Questionnaire ◽  
Phase 3 ◽  
Double Blind ◽  
Acute Medication ◽  
R Domain

Background Efficacy of galcanezumab in chronic migraine has been demonstrated in a pivotal Phase 3 study. Here, we assess efficacy in patients who have failed ≥2 and ≥1 prior migraine preventives for efficacy and/or safety reasons, and in those who never failed. Study design/methods REGAIN (NCT02614261) was a Phase 3, randomized, double-blind, placebo-controlled study in patients with chronic migraine. Patients were randomized 2:1:1 to receive placebo, galcanezumab 120 mg/240 mg once monthly during a double-blind treatment period lasting three months. Subgroup analyses were conducted among patients who failed ≥2 and ≥1 prior preventives and who never failed previously. Outcomes assessed were change from baseline in number of monthly migraine headache days, proportion of patients with ≥50% and ≥75% response (reduction in monthly migraine headache days), change in number of monthly migraine headache days with acute medication use and change in patient functioning per Migraine-Specific Quality of Life Questionnaire Role Function Restrictive (MSQ RF-R) domain score. Results Treatment with galcanezumab versus placebo resulted in significant improvements ( p < 0.01) in overall reduction (Months 1–3) from baseline in the number of monthly migraine headache days in patients with prior failures (LS mean change [SE]: ≥2 prior failures: galcanezumab 120 mg: −5.35 (0.71); galcanezumab 240 mg: −2.77 (0.66); placebo: −1.01 (0.54); ≥1 prior failures: galcanezumab 120 mg: −5.53 (0.60), galcanezumab 240 mg: −3.53 (0.59); placebo: −2.02 (0.49). Similarly, significant results were seen with galcanezumab versus placebo for ≥50% and ≥75% response rates, reductions in acute medication use and improvements in MSQ RF-R domain score. In the subgroup with no prior preventive failures, results were statistically significant for the 240 mg galcanezumab group versus placebo on all outcome measures, and for the 120 mg group on the reduction in migraine headache days with acute medication use. There was also a higher placebo response observed in the patients with no prior preventive failures. Conclusion Galcanezumab is consistently efficacious versus placebo in reducing monthly migraine headache days and several other key outcomes in patients with chronic migraine who have failed ≥2 or ≥1 preventives previously. In the subgroup with no prior failures, greater numerical differences were seen with galcanezumab, but statistical separation from placebo varied by dose and outcome. Clinicaltrials.gov identifier number NCT02614261.

scholarly journals cAMP activates an ATP-permeable pathway in neonatal rat cardiac myocytes

2000 ◽  
Vol 279 (1) ◽  
pp. C173-C187 ◽  
Author(s):  
Alan S. Lader ◽  
Yong-Fu Xiao ◽  
Catherine R. O'Riordan ◽  
Adriana G. Prat ◽  
G. Robert Jackson ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Single Channel ◽  
Atp Release ◽  
Neonatal Rat ◽  
Luciferase Assay ◽  
Neonatal Rat Cardiac Myocytes ◽  
Single Channel Currents ◽  
Rat Cardiac Myocytes ◽  
Camp Stimulation ◽  
R Domain

The molecular mechanisms associated with intracellular ATP release by the heart are largely unknown. In this study the luciferin-luciferase assay and patch-clamp techniques were used to characterize the pathways responsible for ATP release in neonatal rat cardiac myocytes (NRCM). Spontaneous ATP release by NRCM was significantly increased after cAMP stimulation under physiological conditions. cAMP stimulation also induced an anion-selective electrodiffusional pathway that elicited linear, diphenylamine-2-carboxylate (DPC)-inhibitable Cl− currents in either symmetrical MgCl2 or NaCl. ATP, adenosine 5′- O-(3-thiotriphosphate), and the ATP derivatives ADP and AMP, permeated this pathway; however, GTP did not. The cAMP-induced ATP currents were inhibited by DPC and glibenclamide and by a monoclonal antibody raised against the R domain of the cystic fibrosis transmembrane conductance regulator (CFTR). The channel-like nature of the cAMP-induced ATP-permeable pathway was also determined by assessing protein kinase A-activated single channel Cl− and ATP currents in excised inside-out patches of NRCM. Single channel currents were inhibited by DPC and the anti-CFTR R domain antibody. Thus the data in this report demonstrate the presence of a cAMP-inducible electrodiffusional ATP transport mechanism in NRCM. Based on the pharmacology, patch-clamping data, and luminometry studies, the data are most consistent with the role of a functional CFTR as the anion channel implicated in cAMP-activated ATP transport in NRCM.

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