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PubMed2000

Counselling couples and donors for oocyte donation: the decision to use either known or anonymous oocytes.

In order to avoid a long waiting period, the Centre for Reproductive Medicine of the Free University of Brussels suggests that couples in need of donor oocytes search for a donor among family and friends. Recipient couples can choose between two types of donation: known donation, i.e. treatment with the oocytes of the donor recruited by the couple, or anonymous donation, i.e. an exchange of the donor recruited by the couple with a donor recruited by another couple in order to ensure anonymity between donor and recipients. In total, 144 couples were counselled by a psychologist in the decision-making process with regard to the kind of donation to be used. Some 68.8% of the recipient couples preferred known donation. This choice was mainly motivated by reasons related to fears associated with anonymity, such as fear of the unknown origin of genetic material and the trust that couples had in 'their' donor. Almost one-third of the couples opted to use anonymous oocytes. The desire to establish explicit boundaries between the two families involved was the major motivation for this choice. Approximately 44% of the couples were willing to tell the child about the oocyte donation.

Adult↗

PubMed2001

Psychosocial characteristics of infertile couples: a study by the 'Heidelberg Fertility Consultation Service'.

BACKGROUND: The aim of the study was to identify differences in psychological characteristics between couples with fertility disorders, especially idiopathic infertility, and a representative sample. MATERIAL AND METHODS: A total of 564 couples was examined using psychological questionnaires pertaining to sociodemographic factors, motives for wanting a child, dimensions of life satisfaction and couple relationships, physical and psychic complaints, and a personality inventory. RESULTS: Specific to our sample was the high educational level of the couples, and the large number with idiopathic infertility (27% of all diagnoses). There were no remarkable differences in psychological variables between the infertile couples and a representative sample, except that the infertile women showed higher scores on the depression and anxiety scales. Couples with idiopathic infertility showed no remarkable differences in the questionnaire variables compared with couples with other medical diagnoses of infertility. CONCLUSIONS: A typical psychological profile for infertile couples could not be identified using standardized psychometric rating methods. This may be an effect of the specific characteristics of our sample. For some couples, the infertility crisis can be seen as a cumulative trauma, which indicates that these couples have a marked need for infertility counselling.

Adaptation, Psychological↗

PubMedDate not supplied

From "death sentence" to "good cancer": couples' transformation of a prostate cancer diagnosis.

BACKGROUND: While little is known about the couple's process of moving from diagnosis of prostate cancer to treatment, it is acknowledged that cancer-and prostate cancer in particular-affects the couple, not just the patient. This highlighted the need to illuminate this process as a foundation for development of nursing interventions. OBJECTIVES: To describe the experience of men who are diagnosed with prostate cancer and their wives, from the time of diagnosis through staging to the completion of radical prostatectomy. METHODS: A qualitative cross-sectional approach was used to elicit couples' experiences from diagnosis to the time of the interview including their response to diagnosis, their treatment decision-making process, and how the couple moved from the decision to have surgery through the staging process to the time that the surgery was completed. A total of 20 couples participated. RESULTS: Analysis of the data revealed that a number of themes related to the couples' process of moving from diagnosis to treatment. Initially, the diagnosis of prostate cancer represented a loss of control that led these couples to put themselves through a "crash course" on prostate cancer. The information gathered led these couples to conclude that prostate cancer was "good cancer." This enabled them to refocus their energies and start their "quest for the best" treatment and surgeon. Once this was accomplished, the couples began to prepare for surgery that culminated in the turning over of complete control to the surgeon and hospital staff at the time of surgery. CONCLUSIONS: The participants discovered they were able to manage the demands presented by the intrusion of a cancer diagnosis and mount a response to what at first threatened to be a "death sentence." By engaging in the challenge of gathering a volume of facts and a variety of details, they could make informed decisions. Couples were able to regain a sense of control through the engagement in decision-making related to treatment, surgeon, and hospital, and through the transformation of the meaning of the malignant diagnosis to that of a "good cancer."

Adaptation, Psychological↗

PubMed1989

How does posture affect coupling in the lumbar spine?

There is evidence to suggest that abnormal coupling patterns in the lumbar spine may be an indicator of low-back problems. To quantify the normal coupling patterns, fresh cadaveric human lumbar spine specimens (L1-S1) were used. A pure axial torque or lateral bending moment of 10 N-m (in five equal steps) was applied to the specimen, in five spinal postures, and three-dimensional motions were measured at the five vertebral levels. The results indicated that the coupling patterns changed significantly with the intervertebral level. For example, in neutral posture, the left axial torque produced coupled lateral bending, which varied from approximately 2 degrees right lateral bending at L1-2, to approximately 0 degrees at L3-4, and to approximately 2.5 degrees left lateral bending at L5-S1. Additionally, there was coupled flexion of approximately 1 degrees to 2 degrees at all levels. Application of left lateral bending moment resulted in approximately 1.7 degrees of coupled right axial rotation at all levels, except at L1-L2, where it was 0 degrees. Additionally, there was coupled flexion of 0.7 degrees to 2 degrees at all levels. For example, at the L2-3 level, the left axial torque produced coupled right lateral bending that ranged from approximately 0.5 degrees at full extension to approximately 2.5 degrees at full flexion. There was also accompanying coupled flexion of approximately 0.4 degrees to 1.7 degrees. Application of left lateral bending moment at the L2-3 level produced axial rotation of approximately 2.5 degrees, which did not vary with the posture, while the other coupled motion varied from approximately 1.7 degrees flexion at full extension posture to approximately 0.8 degrees extension at full flexion posture.

Biomechanical Phenomena↗

PubMed1996

Effects of posture and structure on three-dimensional coupled rotations in the lumbar spine. A biomechanical analysis.

STUDY DESIGN: A biomechanical lumbar spine model was constructed to simulate three-dimensional spinal kinematics under the application of pure moments. Parametric analysis of the model allowed for the estimation of how much of the coupled motions could be predicted by the lumbar lordosis and the intrinsic mechanical properties of the spine. OBJECTIVES: To evaluate the relative effects of lordosis and intrinsic mechanical spine properties on the magnitude and direction of coupled rotations. SUMMARY OF BACKGROUND DATA: Clinical evidence suggests that abnormal coupled motion in the lumbar spine may be an indicator of low back disorders. METHODS: The biomechanical lumbar spine model consisted of five vertebrae separated by intervertebral joints that provided three rotational degrees of freedom. In vitro experimental data, obtained from nine fresh-frozen (L1-S1) cadaveric specimens, were used to establish the mechanical properties of the intervertebral joints. Two different submodels were considered in simulating the three-dimensional intervertebral rotations in response to the applied moments. In the first, it was assumed that the coupled motions were generated solely as a result of the vertebral orientation caused by lordosis. In the second, additional intrinsic motion coupling was assumed. RESULTS: Intervertebral coupling was partially predicted by lumbar lordosis; however, the inclusion of intrinsic mechanical coupling dramatically improved the simulation of the intervertebral rotations (root mean square error < 1 degree). Comparison of the results from the two models demonstrated that the lumbar lordosis and intrinsic mechanical properties of the spine had about an equal effect in predicting the coupling between axial rotation and lateral bending. In contrast, coupled flexion, associated with lateral bending, was almost fully accounted for by the presence of lumbar lordosis. CONCLUSIONS: The lumbar lordosis and intrinsic mechanical properties of the spine were equally important in predicting the magnitude and direction of the coupled rotations.

Adult↗

PubMed2007

Effects of bone oscillator coupling method, placement location, and occlusion on bone-conduction auditory steady-state responses in infants.

OBJECTIVE: The aim of these experiments was to investigate procedures used when estimating bone-conduction thresholds in infants. The objectives were: (i) to investigate the variability in force applied using two common bone-oscillator coupling methods and to determine whether coupling method affects threshold estimation, (ii) to examine effects of bone-oscillator placement on bone-conduction ASSR thresholds, and (iii) to determine whether the occlusion effect is present in infants by comparing bone-conduction ASSR thresholds for unoccluded and occluded ears. DESIGN: Experiment 1A: The variability in the amount of force applied to the bone oscillator by trained assistants (n = 4) for elastic-band and hand-held coupling methods was measured. Experiment 1B: Bone-conduction behavioral thresholds in 10 adults were compared for two coupling methods. Experiment 1C: ASSR thresholds and amplitudes to multiple bone-conduction stimuli were compared in 10 infants (mean age: 17 wk) using two coupling methods. Experiment 2: Bone-conduction ASSR thresholds and amplitudes were compared for temporal, mastoid and forehead oscillator placements in 15 preterm infants (mean age: 35 wk postconceptual age (PCA)). Experiment 3: Bone-conduction ASSR thresholds, amplitudes and phase delays were compared in 13 infants (mean age: 15 wk) for an unoccluded and occluded test ear. All infants that participated had passed a hearing screening test. RESULTS: Experiment 1A: Coupling method did not significantly affect the variability in force applied to the oscillator. Experiment 1B: There were no differences in adult bone-conduction behavioural thresholds between coupling methods. Experiment 1C: There was no significant difference between oscillator coupling method or significant frequency x coupling method interaction for ASSR thresholds or amplitudes in the young infants tested. However, there was a nonsignificant 9-dB better threshold at 4000 Hz for the elastic-band method. Experiment 2: Mean bone-conduction ASSR thresholds for the preterm infants were not significantly different for the temporal and mastoid placements. Mean ASSR thresholds for the forehead placement were significantly higher compared to the other two placements (12-18 dB higher on average). Mean ASSR amplitudes were significantly larger for the temporal and mastoid placements compared to the forehead placement. Experiment 3: There was no difference in mean ASSR thresholds, amplitudes or phase delays for the unoccluded versus occluded conditions. CONCLUSIONS: Trained assistants can apply an appropriate amount of force to the bone oscillator using either the elastic-band or hand-held method. Coupling method has no significant effect on estimation of bone-conduction thresholds; therefore, either may be used clinically provided assistants are appropriately trained. For preterm infants, there are no differences in ASSRs when the oscillator is positioned at the temporal or mastoid placement. However, thresholds are higher and amplitudes are smaller for the forehead placement, consequently, a forehead placement should be avoided for clinical testing. There does not appear to be a significant occlusion effect in young infants; therefore, it may be possible to do bone-conduction testing with ears unoccluded or occluded without applying a correction factor, although further research is needed to confirm this finding.

Acoustic Stimulation↗

PubMed1988

The effect of photoreceptor coupling and synapse nonlinearity on signal:noise ratio in early visual processing.

Electrical coupling of vertebrate photoreceptors is well known to improve the signal: noise ratio in the photoreceptor layer for large-area stimuli. For example, if N photoreceptors are perfectly coupled to each other, the signal: noise ratio is improved for stimuli illuminating more than a number M = square root of N of the receptors but is made worse for small-area stimuli illuminating less than M of the N receptors. Using the model of Lamb & Simon (J. Physiol., Lond. 263, 257 (1976], which treats the photoreceptor layer as a square array of cells, each coupled through a resistive gap junction to the four cells around it, we show that the signal:noise ratio for small-area stimuli is much greater than would be expected from a model in which receptors are assumed to be perfectly coupled. Contrary to predictions made assuming perfect coupling, receptor coupling should not prevent rods from detecting single photons, but whether the single photon signal can be detected at the bipolar cell level depends on how signals are read out of the receptor layer. The signal:noise ratio in bipolar cells postsynaptic to the photo-receptor layer is determined partly by synaptic convergence and nonlinearity in synaptic transmission from receptors. If the synaptic gain decreases with light-induced receptor hyperpolarization, as is found experimentally, then receptor coupling can improve the postsynaptic signal:noise ratio for stimuli illuminating only one receptor, even though coupling decreases the presynaptic signal:noise ratio for such stimuli. Moreover, increasing the number of coupled receptors projecting to a bipolar cell can improve the signal:noise ratio for localized stimuli if the synapse is sufficiently nonlinear (although, for the degree of nonlinearity seen in lower vertebrates, synaptic convergence makes the ratio worse for the single photon event). The fact that receptor coupling and synaptic convergence can, under some circumstances, improve the signal:noise ratio in bipolar cells suggests a principle of retinal design that may compete with the requirements of high spatial resolution.

Animals↗

PubMed2000

The labile brain. I. Neuronal transients and nonlinear coupling.

In this, the first of three papers, the nature of, and motivation for, neuronal transients is described in relation to characterizing brain dynamics. This paper deals with some basic aspects of neuronal dynamics, interactions, coupling and implicit neuronal codes. The second paper develops neuronal transients and nonlinear coupling in the context of dynamic instability and complexity, and suggests that instability or lability is necessary for adaptive self-organization. The final paper addresses the role of neuronal transients through information theory and the emergence of spatio-temporal receptive fields and functional specialization. By considering the brain as an ensemble of connected dynamic systems one can show that a sufficient description of neuronal dynamics comprises neuronal activity at a particular time and its recent history This history constitutes a neuronal transient. As such, transients represent a fundamental metric of neuronal interactions and, implicitly, a code employed in the functional integration of brain systems. The nature of transients, expressed conjointly in distinct neuronal populations, reflects the underlying coupling among populations. This coupling may be synchronous (and possibly oscillatory) or asynchronous. A critical distinction between synchronous and asynchronous coupling is that the former is essentially linear and the latter is nonlinear. The nonlinear nature of asynchronous coupling enables the rich, context-sensitive interactions that characterize real brain dynamics, suggesting that it plays a role in functional integration that may be as important as synchronous interactions. The distinction between linear and nonlinear coupling has fundamental implications for the analysis and characterization of neuronal interactions, most of which are predicated on linear (synchronous) coupling (e.g. cross-correlograms and coherence). Using neuromagnetic data it is shown that nonlinear (asynchronous) coupling is, in fact, more abundant and can be more significant than synchronous coupling.

Brain↗

PubMed2005

Excitation functions of coupling.

The responses of nonlinear dynamics of two classes to coupling are investigated. It is shown both analytically and numerically that coupling has an excitation ability in a network of the linearly coupled systems. That is, when an uncoupled system is degenerated to a stable steady state from a limit cycle but in the "marginal" state due to the system parameter, an appropriate coupling strength can excite the limit cycle such that the coupled systems exhibit synchronous oscillation; when the uncoupled system is in a stable limit cycle but close to a chaotic attractor, a certain coupling strength can induce the chaotic attractor such that the coupled systems reach chaotic synchronization. Such excitation functions of coupling are different from its traditional role where coupling mainly synchronizes the coupled systems with the original dynamics of the uncoupled system.

Journal Article↗

PubMed2006

Dynamical behavior of hydrodynamic Lyapunov modes in coupled map lattices.

In our previous study of hydrodynamic Lyapunov modes (HLMs) in coupled map lattices, we found that there are two classes of systems with different lambda-k dispersion relations. For coupled circle maps we found the quadratic dispersion relations lambda approximately k2 and lambda approximately k for coupled standard maps. Here, we carry out further numerical experiments to investigate the dynamic Lyapunov vector (LV) structure factor which can provide additional information on the Lyapunov vector dynamics. The dynamic LV structure factor of coupled circle maps is found to have a single peak at omega=0 and can be well approximated by a single Lorentzian curve. This implies that the hydrodynamic Lyapunov modes in coupled circle maps are nonpropagating and show only diffusive motion. In contrast, the dynamic LV structure factor of coupled standard maps possesses two visible sharp peaks located symmetrically at +/- omega. The spectrum can be well approximated by the superposition of three Lorentzian curves centered at omega=0 and +/-omegau, respectively. In addition, the omega-k dispersion relation takes the form omegau=cuk for k --> 2pi/L. These facts suggest that the hydrodynamic Lyapunov modes in coupled standard maps are propagating. The HLMs in the two classes of systems are shown to have different dynamical behavior besides their difference in spatial structure. Moreover, our simulations demonstrate that adding damping to coupled standard maps turns the propagating modes into diffusive ones alongside a change of the lambda-k dispersion relation from lambda approximately k to lambda approximately k2. In cases of weak damping, there is a crossover in the dynamic LV structure factors; i.e., the spectra with smaller k are akin to those of coupled circle maps while the spectra with larger k are similar to those of coupled standard maps.

Journal Article↗

PubMed1989

Intact Chloroplasts Show Ca-Gated Switching between Localized and Delocalized Proton Gradient Energy Coupling (ATP Formation).

Intact chloroplasts were compared to isolated thylakoids as to whether storage of the organelle in high KCl medium caused the energy coupling reactions to show a delocalized or a localized proton gradient energy coupling response. With isolated thylakoids, the occurrence of one or the other energy coupling mode can be reversibly controlled by the concentration of mono- and divalent cations used for the thylakoid storage media. Calcium was shown to be the key ion and previous evidence suggested a Ca(2+)-controlled gating of H(+) fluxes in the thylakoid membrane system (G Chiang, RA Dilley [1987] Biochemistry 26: 4911-4916). Isolated, intact chloroplasts, which retained the outer envelope membranes during the 30 min or longer storage treatments in various concentrations of KCl and CaCl(2) (with sorbitol to maintain iso-osmotic conditions), were osmotically burst in a reaction cuvette and within 3 minutes were assayed for either a localized or a delocalized proton gradient energy coupling (ATP formation) mode. The intact chloroplast system was analogous to isolated thylakoids, with regard to the effects of KCl and CaCl(2) on the energy coupling mode. For example, adding 100 millimolar KCl to the intact organelle storage medium resulted in the subsequent ATP formation assay showing delocalized proton gradient coupling just as with isolated thylakoids. Adding 5 millimolar CaCl(2) to the 100 millimolar KCl storage medium resulted in a localized proton gradient coupling mode. Suspending thylakoids in stromal material previously isolated from intact chloroplast preparations and testing the energy coupling response showed that the stromal milieu has enough Ca(2+) to cause the localized coupling response even though there was about 80 millimolar K(+) in the intact chloroplasts used in this study (determined by atomic absorption spectrophotometry). Extrapolating the intact chloroplast data to the whole leaf level, we suggest that proton gradient energy coupling is normally of the localized mode, but under certain conditions it could be either localized or delocalized, depending on factors that affect the putative Ca(2+)-regulated proton flux gating function.

Journal Article↗

PubMed1996

Galvanic corrosion and cytotoxic effects of amalgam and gallium alloys coupled to titanium.

The aim of this study was to examine and compare the galvanic corrosion of a conventional, a dispersed high-copper, and a palladium-enriched spherical high-copper amalgam and a gallium alloy coupled to titanium in saline and cell culture solutions, and to evaluate the effects of the couples on cultured cells. The potentials and charge transfers between amalgams and titanium were measured by electrochemical corrosion methods. Cytotoxicity of the couples, as indicated by the uptake of neutral red vital stain, was determined in 24-h direct contact human gingival fibroblast cell cultures. Results of this study indicated that before connecting the high-copper amalgams to titanium, the amalgams exhibited more positive potentials which resulted in initial negative charge transfers, i.e. corrosion of titanium. However, this initial corrosion appeared to cause titanium to passivate, and a shift in galvanic currents to positive charge transfers, i.e. corrosion of the amalgam samples. Lower galvanic currents were measured for the amalgam-titanium couples as compared to the gallium alloy-titanium couple. Coupling the conventional or the palladium-enriched high-copper amalgams to titanium did not significantly affect the uptake of neutral red as compared to cells not exposed to any test alloy. However, significant cytotoxic effects were observed when the dispersed-type high-copper amalgam and the gallium alloy were coupled to titanium. Even though the corrosion currents measured for these couples were less than gold alloys coupled to amalgam, these results suggest there is the potential for released galvanic corrosion products to become cytotoxic. These data warrant further investigations into the effects of coupling amalgam and gallium alloys to titanium in the oral environment.

Alloys↗

PubMed2000

Relationship satisfaction of Mexican American and non-Hispanic white American interethnic couples: issues of acculturation and clinical intervention.

Despite the increasing prevalence of interethnic marriages, remarkably little empirical literature exists for guiding clinical interventions offered to these couples. This study compared the marriages of 72 couples with one Mexican-American partner and one non-Hispanic White American partner, 75 Mexican-American couples, and 66 non-Hispanic White couples. Overall, the interethnic couples were more similar to non-Hispanic White couples than they were to Mexican-American couples across multiple domains, with the latter group indicating modestly higher levels of relationship distress. Among interethnic couples, Mexican-American wives' level of acculturation related significantly to both their own marital- and parental-role orientation and to distress in their relationships with children, as well as to their husbands' marital distress regarding child rearing and the couple's interactions regarding finances. Implications for clinical interventions with Mexican- and White-American interethnic couples are discussed.

Acculturation↗

PubMed1994

Analysis of the spatial-frequency-dependent DQE of optically coupled digital mammography detectors.

The effect of optical coupling efficiency on the spatial-frequency-dependent propagation of signal and noise is considered for x-ray image detectors for digital mammography in which a phosphor screen is optically coupled to a charge-coupled device (CCD) image array. For experimental purposes, optical coupling between a Gd2O2S:Tb phosphor screen and a CCD image array was provided by relay lenses. Neutral density filters were inserted between the lenses to vary the optical coupling efficiency without altering the inherent spatial resolution. The total coupling efficiency, defined as the number of electrons (e-) recorded in the CCD per x-ray interaction in the phosphor, was calculated in each case. The modulation transfer function, and the contributions to the total noise power spectrum (NPS) of x-ray quantum noise, secondary quantum noise, and inherent detector noise were measured as a function of coupling efficiency. These data were used to calculate the spatial-frequency-dependent detective quantum efficiency [DQE(f)]. The NPS due to x-ray quantum noise had a significant spatial-frequency dependence for coupling efficiencies of more than 9 e- per x-ray interaction, but little spatial-frequency dependence for coupling efficiencies of less than 2 e- per x-ray interaction. These results indicate that to preserve high spatial-frequency values of DQE(f), and to ensure that images are x-ray quantum-noise limited at high spatial frequencies, a coupling efficiency on the order of 10 e- per x-ray interaction is required.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrons↗

PubMed2005

Gq-mediated activation of c-Jun N-terminal kinase by the gastrin-releasing peptide-preferring bombesin receptor is inhibited upon costimulation of the Gs-coupled dopamine D1 receptor in COS-7 cells.

G protein-coupled receptors (GPCRs) of Gi- or Gq-coupling specificity are effectively linked to activation of the c-Jun N-terminal kinase (JNK) cascade. However, little is known with regard to the regulation of JNK by Gs-coupled receptors. In this report, we used COS-7 cells transfected with the dopamine D1 receptor (D1R) to illustrate the signaling mechanism for Gs-mediated JNK activation. Stimulation of D1R triggered a weak but significant elevation of JNK activity in a time- and dose-dependent manner. This D1R-mediated JNK activation required the participation of Gbetagamma, Src-like kinases, and small GTPases, whereas disruptions of cAMP-, phosphoinositide-3-kinase-, and epidermal growth factor receptor-mediated signaling had no effect. Costimulation of D1R with GPCRs of other coupling specificities resulted in differential activation profiles of JNK. Activation of Gs-coupled D1R weakly potentiated the JNK activation induced by the Gi-coupled opioid receptor-like receptor, but it exhibited a significant inhibitory effect on the kinase activity triggered by the Gq-coupled gastrin-releasing peptide-preferring bombesin receptor (GRPR). Administration of Spadenosine-3',5'-cyclic monophosphorothioate triethylamine (a cAMP analog that mimics the Gs/cAMP signal) also suppressed the JNK activation mediated by Gq-coupled GRPR, as well as the Ca2+-induced kinase activation upon thapsigargin treatment. Moreover, the Ca2+ signal from GRPR synergistically potentiated the D1R-triggered cAMP elevation when the two receptors were stimulated simultaneously. Taken together, our results demonstrated that stimulation of Gs-coupled receptors in COS-7 cells not only enhanced the JNK activity, but also exhibited a "tuning" effect on the kinase activation mediated by GPCRs of other coupling specificities.

Animals↗

PubMed2002

Negative and positive regulatory epitopes in the C-terminal domains of the human B1 and B2 bradykinin receptor subtypes determine receptor coupling efficacy to G(q/11)-mediated [correction of G(9/11)-mediated] phospholipase Cbeta activity.

The human B1 bradykinin (BK) receptor (B1R) is more efficacious than the human B2 BK receptor (B2R) in both ligand-independent and agonist-dependent coupling to G(q/11)-mediated phospholipase Cbeta activity. In fact, B1R is constitutively active, whereas B2R exhibits little if any constitutive activity. To evaluate the role of the C-terminal domain in receptor G(q/11) coupling, we constructed chimeric and C-terminally truncated receptors. The slopes of the increase in basal and agonist-dependent cellular phosphoinositide hydrolysis as a function of receptor density in transiently transfected human embryonic kidney 293 cells provided parameters of receptor coupling. Exchanging the C-terminal domains between the two receptors revealed that these domains are largely responsible for the difference in coupling. B1R truncation showed that this receptor does not directly depend on the C-terminal domain for efficient coupling, although coupling is dramatically augmented by residues in the membrane-distal portion of the domain downstream from Tyr(327). On the other hand, coupling of B2R is absolutely dependent on a membrane-proximal epitope in the C-terminal domain upstream from Lys(315). This epitope is adjacent to a basic residue, Arg(311), which exerts an inhibitory effect on coupling. Arg(311) is not conserved in B1R, and complementary mutations in B2R and B1R showed that this residue, together with previously identified serines and threonines, acts to attenuate the coupling efficacy of B2R. Therefore, the C-terminal domain participates intimately in the efficacy of B1R and B2R G(q/11) coupling by contributing both positive and negative regulatory epitopes.

Amino Acid Sequence↗

PubMed2002

Tet(L) and tet(K) tetracycline-divalent metal/H+ antiporters: characterization of multiple catalytic modes and a mutagenesis approach to differences in their efflux substrate and coupling ion preferences.

The Tet(L) protein encoded in the Bacillus subtilis chromosome and the closely related Tet(K) protein from Staphylococcus aureus plasmids are multifunctional antiporters that have three cytoplasmic efflux substrates: a tetracycline-divalent metal (TC-Me(2+)) complex that bears a net single positive charge, Na+, and K+. Tet(L) and Tet(K) had been shown to couple efflux of each of these substrates to influx of H+ as the coupling ion. In this study, competitive cross-inhibition between K+ and other cytoplasmic efflux substrates was demonstrated. Tet(L) and Tet(K) had also been shown to use K+ as an alternate coupling ion in support of Na+ or K+ efflux. Here they were shown to couple TC-Me(2+) efflux to K+ uptake as well, exhibiting greater use of K+ as a coupling ion as the external pH increased. The substrate and coupling ion preferences of the two Tet proteins differed, especially in the higher preference of Tet(K) than Tet(L) for K+, both as a cytoplasmic efflux substrate and as an external coupling ion. Site-directed mutagenesis was employed to test the hypothesis that some feature of the putative "antiporter motif," motif C, of Tet proteins would be involved in these characteristic preferences. Mutation of the A157 in Tet(L) to a hydroxyamino acid resulted in a more Tet(K)-like K+ preference both as coupling ion and efflux substrate. A reciprocal S157A mutant of Tet(K) exhibited reduced K+ preference. Competitive inhibition among substrates and the parallel effects of the single mutation upon K+ preference, as both an efflux substrate and coupling ion, are compatible with a model in which a single translocation pathway through the Tet(L) and Tet(K) transporters is used both for the cytoplasmic efflux substrates and for the coupling ions, in an alternating fashion. However, the effects of the A157 and other mutations of Tet(L) indicate that even if there are a shared binding site and translocation pathway, some elements of that pathway are used by all substrates and others are important only for particular substrates.

Amino Acid Sequence↗

PubMed1999

Preconceptional screening of couples for carriers of cystic fibrosis: a prospective evaluation of effects, costs and savings for different mutation detection methods.

OBJECTIVE: The aim of this study was to perform a prospective evaluation of the effects, costs and savings of a preconceptional screening programme of couples for carriers of cystic fibrosis (CF). METHODS: A decision model for both single-entry two-step (SETS) and double-entry two-step (DETS) couple screening was constructed. Two mutation detection methods were considered: allele-specific oligonucleotide (ASO) hybridisation screening of 32 mutations, with a sensitivity of 90%, and denaturing gradient gel electrophoresis (DGGE), with a sensitivity of 98%. In our model, the following combinations were used: (1) ASO for both steps; (2) DGGE for both steps, and (3) ASO for the first step and DGGE for the second step. The model is demonstrated using figures from the Netherlands, where there is a carrier frequency of 1:30. We estimated the value of different choices and probabilities in a decision tree and determined the costs of screening for CF and the costs of the illness itself. RESULTS: We found that with most of the combinations of mutation detection methods, SETS couple screening could offer positive net savings in the Netherlands. The ASO/DGGE combination resulted in the highest net savings. DETS couple screening for all combinations, including testing with DGGE in both steps, did not show a positive cost-savings balance at all, not even with an uptake rate of 100%. The maximum number of carrier couples identified when screening 100,000 couples with the ASO/DGGE combination was 98 (SETS). This could result in about 25 fewer children born with CF each year in the Netherlands, under the following assumptions: (1) each couple has two children and 10% of couples are unable to have children; (2) of detected carrier couples, 15% decide not to have children and 85% make use of prenatal diagnosis; (3) of those fetuses diagnosed with CF, 80% are aborted, and (4) prenatal diagnosis carries a 0.75% risk of iatrogenic abortion. CONCLUSIONS: The results of this evaluation show that there are no financial objections to the preconceptional screening of couples in the Netherlands when the above-mentioned assumptions apply; thus, further evaluation can concentrate on the balance of the non-economic consequences of screening for participants and for society.

Journal Article↗