Magnesium permeation through mechanosensitive channels： single-current measurements

Compelling evidence shows that intracellular free magnesium [Mg^2＋]i may be a critical regulator of cell activity in eukaryotes. However, membrane transport mechanisms mediating Mg^2＋ influx in mammalian cells are poorly understood. Here, we show that mechanosensitive （MS） cationic channels activated by stretch are permeable for Mg^2＋ ions at different extracellular concentrations including physiological ones. Single-channel currents were recorded from cell-attached and inside-out patches on K562 leukaemia cells at various concentrations of MgCl2 when Mg^2＋ was the only available carrier of inward currents. At 2 mM Mg^2＋, inward mechanogated currents representing Mg^2＋ influx through MS channels corresponded to the unitary conductance of about 5 pS. At higher Mg^2＋ levels, only slight increase of single-channel currents and conductance occurred, implying that Mg^2＋ permeation through MS channels is characterized by strong saturation. At 20 and 90 mM Mg^2＋, mean conductance values for inward currents carried by Mg^2＋ were rather similar, being equal to 6.8 ± 0.5 and 6.4 ± 0.5 pS, respectively. The estimation of the channel-selective permeability according to constant field equation is obviously limited due to saturation effects. We conclude that the detection of single currents is the main evidence for Mg^2＋ permeation through membrane channels activated by stretch. Our single-current measurements document Mg^2＋ influx through MS channels in the plasma membrane of leukaemia cells.     

The application of generalizability theory to surface electromyographic measurements during psychophysiological stress testing: how many measurements are needed?

Generalizability theory is an extension of classical reliability theory that allows multiple sources of measurement error in an experimental design to be investigated simultaneously. In the present study, generalizability theory was used to evaluate measurement error in psychophysiological test procedures used to differentiate tension headache patients from normal controls based upon measures of electromyographic (EMG) responding. Thirty-three subjects who met diagnostic criteria for tension-type headache and 40 normal control subjects who rarely or never experienced headache participated in two laboratory sessions. EMG activity of head and neck muscles was recorded while subjects performed baseline, relaxation, choice reaction time, psychomotor tracking, and cold pressor tasks. Variance components were computed for an experimental design having subjects nested within experimenters and crossed with sessions and replications. Generalizability coefficients were computed for combinations of various numbers of sessions and replications. The generalizability of EMG measures was highly variable, depending on the experimental conditions in force. The largest sources of measurement error were attributed to the unique responsiveness of individual subjects under a particular set of treatment conditions. For some stress tests currently in use, data from several testing sessions may need to be averaged in order to achieve acceptable levels of generalizability. Generalizability greater than 0.80 can be expected only rarely when data are collected during a single session. In the research setting, low generalizability may account for the failure of EMG-based stress tests to differentiate tension headache patients from controls during stressful task performance. In the clinical setting, the generalizability of information derived from "stress profiling" or muscle "scanning" techniques, which depend on results obtained during a single testing session, is doubtful.     

Anthropometric measurements by ethnicity in Colombia, 1965–1990

We analyzed the evolution of height in Colombia of cohorts born in the period 1965–1990 by ethnic groups. We found that Afro-Colombian men and women were the tallest: 6 cm taller than indigenous people and 2 cm taller than the rest of the population. We also found that the height gap between Afro-Colombians and others decreased during the period under study by 0.7 cm for both men and women. While improvements were noticeable among the Afro-Colombians and those who chose not to be classified by ethnicity, in the case of the indigenous population only female cohorts registered an average-height increase of 1.5 cm. Moreover, we found that indigenous Colombians were more likely than other ethnic groups to experience an increase in biological well-being as a consequence of an improvement in their socio-economic status, thereby reducing the average-stature gap between them and the rest of the population by 2.1 and 3.6 cm for men and women, respectively.     

Should we take measurements at an intermediate design point?

It is well known that, for estimating a linear treatment effect with constant variance, the optimal design divides the units equally between the two extremes of the design space. If the dose-response relation may be nonlinear, however, intermediate measurements may be useful in order to estimate the effects of partial treatments. We consider the decision of whether to gather data at an intermediate design point: do the gains from learning about nonlinearity outweigh the loss in efficiency in estimating the linear effect? Under reasonable assumptions about nonlinearity, we find that, unless sample size is very large, the design with no interior measurements is best, because with moderate total sample sizes, any nonlinearity in the dose-response will be difficult to detect. We discuss in the context of a simplified version of the problem that motivated this work-a study of pest-control treatments intended to reduce asthma symptoms in children.     

High-field, variable-temperature M?ssbauer effect measurements on oxyhemeproteins

We measured M?ssbauer spectra of human oxyhemoglobin, its isolated beta chains, and of oxymyoglobin from horse and sperm whale in fields of 4 or 6 T between 4.2 and 200 K in order to characterize the electronic state of the oxyheme complex. Diamagnetic sodium nitroprusside measured under the same conditions served as a control. The spectra of all compounds are reproduced adequately by a model that assumes a diagmagnetic iron and treats the quadrupole splitting, the asymmetry parameter and the M?ssbauer linewidth as adjustable parameters. The results provide no indication in the oxyhemeproteins of the excited triplet state that was postulated by Cerdonio and co-workers (Cerdonio, M., Congiu-Castellano, A., Mogno, F., Pispisa, B., Romani, G.L. and Vitale, S. (1977) Proc. Natl. Acad. Sci. USA 74, 398-400) on the basis of susceptibility measurements on oxyhemoglobin.     

Can short-term litter-bag measurements predict long-term decomposition in northern forests?

Plant and Soil - The litter-bag technique has become common in the estimation of the rates of decomposition, but in many cases the bags are incubated for only a short period, raising the issue of...     

The imagination of ‘society’ in measurements of immigrant integration

Abstract

My aim in this contribution is to clarify in which way social scientific measurements of immigrant integration operate as a form of ‘social imagination’, that is, of the routinized and professionalized visualization of social life. Through such measurements, images of ‘society’ are produced that feed into larger social imaginaries. My discussion takes as an example Dutch discourse and research on integration. Crucial to the constitution of society in the Netherlands and many other Western European countries is what I call a culturist discourse that has many similarities to racism. This discourse demarcates the boundaries of society by rendering objectively observable the non-integrated who are considered to reside ‘outside society’. The image of society thereby produced is that of a morally cleansed realm: social problems are relegated to the domain ‘outside society’, consisting of persons in need of integration.     

Can the axial ligand strength be monitored through spectroscopic measurements?

 The influence of the properties of the axial ligands in heme proteins on the electronic structure of the iron(III) ion has been studied through angular overlap calculations. In particular, a correlation between (a) ligand field parameters and spectroscopic data and (b) the reduction potentials of the iron ion is proposed. The results of this approach are discussed with respect to their relevance for the biological function of different heme proteins. Received and accepted: 7 May 1996     

Are exhaled nitric oxide measurements using the portable NIOX MINO repeatable?

Background

Exhaled nitric oxide is a non-invasive marker of airway inflammation and a portable analyser, the NIOX MINO (Aerocrine AB, Solna, Sweden), is now available. This study aimed to assess the reproducibility of the NIOX MINO measurements across age, sex and lung function for both absolute and categorical exhaled nitric oxide values in two distinct groups of children and teenagers.

Methods

Paired exhaled nitric oxide readings were obtained from 494 teenagers, aged 16-18 years, enrolled in an unselected birth cohort and 65 young people, aged 6-17 years, with asthma enrolled in an interventional asthma management study.

Results

The birth cohort participants showed a high degree of variability between first and second exhaled nitric oxide readings (mean intra-participant difference 1.37 ppb, 95% limits of agreement -7.61 to 10.34 ppb), although there was very close agreement when values were categorised as low, normal, intermediate or high (kappa = 0.907, p < 0.001). Similar findings were seen in subgroup analyses by sex, lung function and asthma status. Similar findings were seen in the interventional study participants.

Conclusions

The reproducibility of exhaled nitric oxide is poor for absolute values but acceptable when values are categorised as low, normal, intermediate or high in children and teenagers. One measurement is therefore sufficient when using categorical exhaled nitric oxide values to direct asthma management but a mean of at least two measurements is required for absolute values.     

Reconstructing parameters of the FitzHugh–Nagumo system from boundary potential measurements

We consider distributed parameter identification problems for the FitzHugh–Nagumo model of electrocardiology. The model describes the evolution of electrical potentials in heart tissues. The mathematical problem is to reconstruct physical parameters of the system through partial knowledge of its solutions on the boundary of the domain. We present a parallel algorithm of Newton–Krylov type that combines Newton’s method for numerical optimization with Krylov subspace solvers for the resulting Karush–Kuhn–Tucker system. We show by numerical simulations that parameter reconstruction can be performed from measurements taken on the boundary of the domain only. We discuss the effects of various model parameters on the quality of reconstructions. Action Editor: David Terman     

Gamma-ray thermoluminescence measurements: a record of fallout deposition in Hiroshima?

In certain Hiroshima neighborhoods, radiation measurements using thermoluminescence dosimetry (TLD) exceed what can be explained by the initial gamma-ray doses and uncertainties from the Dosimetry System 2002 (DS02). This problem was not previously recognized as being isolated to certain parts of that city. The ratio between TLD measurements and DS02 dose calculations for gamma rays appear to grow larger than unity up to more than three with increasing ground range, but closer examination shows the excess TLD dose (0.1, 0.2, or possibly up to 0.8 Gray) is correlated with certain neighborhoods and could be due to radioactive fallout. At Nagasaki, the TLD measurements do not show this same excess, probably because there were no TLD measurements taken more than 800 m downwind (eastward) from the Nagasaki hypocenter, so that any small excess TLD dose was masked by larger initial gamma-ray doses of 25–80 Gray in the few downwind samples. The DS02 Report had noted many measurements lower than the DS02 calculation for several Nagasaki TLD samples, independent of ground range. This was explained as being the result of previously unaccounted urban shielding which was observed from Nagasaki pre-bomb aerial photos. However, the Hiroshima excess TLD dose issue was not resolved. If the excess TLD doses at Hiroshima are an indication of fallout, it may be possible to use additional TLD studies to make better estimates of the locations and radiation doses to survivors from the fallout after the bombings at both cities.     

Can the patellar tendon moment arm be predicted from anthropometric measurements?

The purpose of this study was to examine the relations between patellar tendon moment arm length and several relevant anthropometric characteristics of 22 healthy men. The patellar tendon moment arm length was measured using magnetic resonance imaging with two different methods: (1) measurement of patellar tendon moment arm length (d(PT)) with respect to the tibiofemoral contact point (d(PTCP)) and (2) measurement of d(PT) with respect to the intersection point of the anterior and posterior cruciate ligament (d(PTIP)). Pearson correlation coefficients and a stepwise linear regression analysis were used to examine the relationships between the d(PT) and anthropometric measurements taken. Furthermore, a Student's t-test was used to determine differences between the d(PTCP) and d(PTIP) values. Only knee circumference was a significant d(PTCP) predictor (P < 0.05) but with a very low R2 (0.139). None of the anthropometric parameters examined was found to be a significant d(PTIP) predictor. The correlation coefficients ranged from -0.04 to 0.42. The d(PTIP) values were significantly higher (by 0.84-1.89 cm) than the d(PTCP) values (P < 0.05). These results are in disagreement with previous in vitro findings that d(PT) variance may be explained by knee joint size differences. Hence, existing imaging-based methodologies remain necessary for accurate quantification of the patellar tendon moment arm.     

Kinetic measurements give new insights into lipid membrane permeabilization by α-synuclein oligomers

Interactions of oligomeric aggregates of the intrinsically disordered protein α-synuclein with lipid membranes appear to play an important role in the development of Parkinson's disease. The permeabilization of cellular membranes by oligomers has been proposed to result in neuronal death. The detailed mechanisms by which α-synuclein oligomers permeabilize lipid bilayers remain unknown. Two different mechanisms are conceivable. Oligomers may either insert into membranes forming pores through which small molecules can cross the membrane or their interaction with the membrane may disorder the lipid packing, giving rise to membrane defects. Here we show, using kinetic leakage measurements, that α-synuclein oligomer induced impairment of membrane integrity is not limited to the formation of permanent membrane spanning pores. Fast membrane permeabilization could be observed in a fraction of the large unilamellar vesicles. We have also observed, for the first time, that α-synuclein oligomers cause an enhanced lipid flip-flop. In neuronal cells, most of the α-synuclein is not expected to be present in an oligomeric form, but as monomers. In our in vitro experiments, we find that membrane bound monomeric α-synuclein can only delay the onset of oligomer-induced membrane permeabilization, implying that α-synuclein monomers cannot counteract oligomer toxicity.     

Single-microelectrode voltage clamp measurements of pancreatic β-cell membrane ionic currents in situ

A conventional patch clamp amplifier was used to test the feasibility of measuring whole-cell ionic currents under voltage clamp conditions from -cells in intact mouse islets of Langerhans perifused with bicarbonate Krebs buffer at 37°C. Cells impaled with a high resistance microelectrode (ca. 0.150 G) were identified as -cells by the characteristic burst pattern of electrical activity induced by 11 mm glucose. Voltage-dependent outward K⁺ currents were enhanced by glucose both in the presence and absence of physiological bicarbonate buffer and also by bicarbonate regardless of the presence or absence of glucose. For comparison with the usual patch clamp protocol, similar measurements were made from single rat -cells at room temperature; glucose did not enhance the outward currents in these cells. Voltage-dependent inward currents were recorded in the presence of tetraethylammonium (TEA), an effective blocker of the K⁺ channels known to be present in the -cell membrane. Inward currents exhibited a fast component with activation-inactivation kinetics and a delayed component with a rather slow inactivation; inward currents were dependent on Ca²⁺ in the extracellular solution. These results suggest the presence of either two types of voltage-gated Ca²⁺ channels or a single type with fast and slow inactivation. We conclude that it is feasible to use a single intracellular microelectrode to measure voltage-gated membrane currents in the -cell within the intact islet at 37°C, under conditions that support normal glucose-induced insulin secretion and that glucose enhances an as yet unidentified voltage-dependent outward K⁺ current.The authors are pleased to thank Dr. M.X. Li for performing some of the experiments in Fig. 2, Dr. A. Sherman for many illuminating discussions, and Drs. J. Rinzel and N. Sheppard for support. D.M. was supported in part by a National Institutes of Health training grant to The Johns Hopkins University, Department of Biomedical Engineering. Thanks are also given to B. Chidakel for electronic design and construction.     

What measurements are necessary for a comprehensive evaluation of the peripheral arterial circulation?

Several methods are available to detect atherosclerotic lesions with a severe degree of stenosis (>70%), but the diagnosis of atherosclerotic lesions with no stenosis or with a minor degree of stenosis (<20%), is problematic. Hemodynamics associated with stenotic lesions are well described by the relationship of blood pressure and blood flow velocity, both as a function of time and localization (along the length and cross-section of the vessel). The use of this relationship in the clinic is difficult because no precise information is available about the geometry and branching of arteries, blood viscosity, and the velocity distribution over the cross-sectional area of the blood vessel. Besides, the invasiveness of the technique to measure arterial pressure as a function of time and localization does not allow routine application in patients. Because of these limitations, alternative methods have been developed. The degree and extensiveness of atherosclerotic disease can, for instance, be estimated from the changes in maximum blood flow velocity and in velocity profile, i.e., velocity distribution along the cross-section of the vessel. Moreover, the delay between simultaneously recorded arterial blood flow velocity tracings (pulse-wave velocity determination) is used to assess the elastic properties of the vessel. Changes in velocity profile occur at relatively slight degrees of arterial stenosis (around 20%), so that determination of these profiles along diseased arteries may contribute to the early diagnosis of atherosclerotic lesions. In man, transcutaneous information about the maximum and mean blood flow velocities over the cross-sectional area of the artery as an instantaneous function of time as well as the flow pattern can be obtained online with continuous wave Doppler flowmeters, at least when audio spectrum analysis is used as a processing technique. Velocity profiles can be determined with multichannel pulsed Doppler systems if the resolution of the system is adequate and a sufficient number of sample volumes can be obtained, limiting the interpolation between these samples. The on-line recording of velocity profiles can be facilitated by combining the pulsed Doppler device with either a velocity imaging system or a B-mode scan. In systems with a high resolution (sample distance 0.5 mm), one should be able to detect local disturbances in the velocity profile at the site of the lesion (due to local increases in shear stress) and proximal to the lesion (due to reflections), so that lesions with a minor degree of stenosis can be detected. In resistive systems (e.g., internal carotid arteries) in which the relationship between pressure and velocity changes during the cardiac cycle is relatively simple, the elasticity of the arterial wall can be determined by relating the relative diameter changes of the vessel, determined on-line with multichannel pulsed Doppler systems, to the instantaneous velocity pulse. Although the detection of atherosclerotic lesions at an early stage of the disease with sophisticated Doppler devices looks promising, further clinical evaluation is required.     

What do measurements of molecular biomarkers in different body fluids really tell us?

Molecular or biochemical biomarkers of joint metabolism offer promise in helping us understand joint pathology, its detection and treatment. But they have often been studied alone and in only one body fluid. Although the synovial joint is usually the focus of most arthritis pathology, it is often difficult, for a variety of reasons, to obtain synovial fluid that should best reflect changes in biomarkers related to pathology. It is therefore very important to see whether analyses of more readily obtainable sera and urine also reflect changes in synovial fluid. Catterall and colleagues, in a paper in Arthritis Research & Therapy that examines very early biomarker changes following joint injury, provide us with some insights into these important questions. As the study was very small and examined very early changes following joint injury, prior to onset of any recognisable pathology, we look forward to future larger biomarker studies of this kind in patients with clinically defined arthritic changes to which we can relate biomarker data.     

Cutaneous thermal thresholds—the reproducibility of their measurements and the effect of gender

The present study evaluated the reproducibility of measurements of the forearm thresholds for warm (WT) and cold (CT) sensation, and their dependence on gender. The Middlesex Thermal Testing System was used for this purpose. CT did not differ between the five consecutive trials, whereas WT fell significantly. A minimum of two trial tests are therefore recommended prior to the assessment of WT. Furthermore, CT and WT were induced by significantly smaller skin temperature changes (lower thresholds) in females as compared to males. Should this gender specific difference in thermosensitivity also be observed in other skin regions, then females would be more sensitive to thermal stimulation than males.     

Shock wave therapy for femoral head necrosis—Pressure measurements inside the femoral head

There is a persisting need for effective therapies of femoral head necrosis, a common bone disease. Promising clinical results have been stated for the treatment with extracorporeal shock waves (ESW). However, the effective remaining pressure in the target region inside the femoral head has never been determined. Aim of this study was to investigate whether ESW are able to propagate through bone without an excessive loss of pressure. The remaining ESW pressure generated by an electromagnetic device after passing a certain intraosseous distance within the femoral head was measured. Standardized holes were drilled in porcine femora and the absorption in relation to reference measurements in degassed water was determined. The results showed continuous attenuation of shock waves in bone. After a clinical relevant intraosseous distance of 10 mm an ESW pressure of ～50% remained.In conclusion, ESW have the potential to reach necrotic regions with therapeutic pressure levels and to effectively treat femoral head necrosis.     

What do we currently know from in vivo bone strain measurements in humans?

Bone strains are the most important factors for osteogenic adaptive responses. During the past decades, scientists have been trying to describe the relationship between bone strain and bone osteogenic responses quantitatively. However, only a few studies have examined bone strains under physiological condition in humans, owing to technical difficulty and ethical restrictions. The present paper reviews previous work on in vivo bone strain measurements in humans, and the various methodologies adopted in these measurements are discussed. Several proposals are made for future work to improve our understanding of the human musculoskeletal system. Literature suggests that strains and strain patterns vary systematically in response to different locomotive activities, foot wear, and even different venues. The principal compressive, tension and engineering shear strain, compressive strain rate and shear strain rate in the tibia during running seem to be higher than those during walking. The high impact exercises, such as zig-zag hopping and basketball rebounding induced greater principal strains and strain rates in the tibia than normal activities. Also, evidence suggests an increase of tibia strain and strain rate after muscle fatigue, which strongly supports the opinion that muscle contractions play a role on the alteration of bone strain patterns.