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1.
A study has been made of the temperature changes associated with the passage of a single impulse in the non-myelinated fibres of the garfish olfactory nerve: and the time course of these temperature changes has been compared with the time course of the electrical events during the action potential. As in other non-myelinated nerves studied the observed temperature changes result from a biphasic initial heat production consisting of a transient evolution of heat (the positive heat) followed by a rapid heat reabsorption (referred to as the negative heat). There is no evidence of any additional phases of initial heat production. At 0 degrees C the measured positive initial heat is 224 mucal/g impulse (937 muJ/g impulse); and the corresponding negative initial heat is 230 mucal/g impulse (962 muJ/g impulse). The residual initial heat is very small, being about -6 mucal/g impulse (-25 muJ/g impulse). In the range 0-10 degrees C there is no significant effect of temperature on the magnitude of either the positive or the negative phases of heat production. The experimental thermal records were analysed to determine the true time course of the temperature changes in the nerve undistorted by the recording system. The time course of the temperature changes does not fit with that of the transmembrane voltage change as represented by the monophasic compound action potential recorded externally from the same point on the nerve. A better fit is obtained if the temperature changes are compared with the square of the voltage change in accordance with the view that the heat derives almost wholly from free energy changes and entropy changes in the membrane capacity. The best fit is obtained if it is assumed that the membrane potential does not discharge to zero during the action potential but that at the peak of the action potential the charge (and hence the p.d.) across the membrane capacity retains about 24% of its resting value.  相似文献   
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BackgroundActive case finding (ACF) may be valuable in tuberculosis (TB) control, but questions remain about its optimum implementation in different settings. For example, smear microscopy misses up to half of TB cases, yet is cheap and detects the most infectious TB cases. What, then, is the incremental value of using more sensitive and specific, yet more costly, tests such as Xpert MTB/RIF in ACF in a high-burden setting?Methods and findingsWe constructed a dynamic transmission model of TB, calibrated to be consistent with an urban slum population in India. We applied this model to compare the potential cost and impact of 2 hypothetical approaches following initial symptom screening: (i) ‘moderate accuracy’ testing employing a microscopy-like test (i.e., lower cost but also lower accuracy) for bacteriological confirmation and (ii) ‘high accuracy’ testing employing an Xpert-like test (higher cost but also higher accuracy, while also detecting rifampicin resistance). Results suggest that ACF using a moderate-accuracy test could in fact cost more overall than using a high-accuracy test. Under an illustrative budget of US$20 million in a slum population of 2 million, high-accuracy testing would avert 1.14 (95% credible interval 0.75–1.99, with p = 0.28) cases relative to each case averted by moderate-accuracy testing. Test specificity is a key driver: High-accuracy testing would be significantly more impactful at the 5% significance level, as long as the high-accuracy test has specificity at least 3 percentage points greater than the moderate-accuracy test. Additional factors promoting the impact of high-accuracy testing are that (i) its ability to detect rifampicin resistance can lead to long-term cost savings in second-line treatment and (ii) its higher sensitivity contributes to the overall cases averted by ACF. Amongst the limitations of this study, our cost model has a narrow focus on the commodity costs of testing and treatment; our estimates should not be taken as indicative of the overall cost of ACF. There remains uncertainty about the true specificity of tests such as smear and Xpert-like tests in ACF, relating to the accuracy of the reference standard under such conditions.ConclusionsOur results suggest that cheaper diagnostics do not necessarily translate to less costly ACF, as any savings from the test cost can be strongly outweighed by factors including false-positive TB treatment, reduced sensitivity, and foregone savings in second-line treatment. In resource-limited settings, it is therefore important to take all of these factors into account when designing cost-effective strategies for ACF.

In this modeling study, Lucia Cilloni and colleagues simulate the cost and epidemiologic impact of active case-finding for tuberculosis in high-burden settings such as India.  相似文献   
3.
GABA modification plays an important role in motor cortical plasticity. We therefore hypothesized that interindividual variation in the responsiveness of the GABA system to modification influences learning capacity in healthy adults. We assessed GABA responsiveness by transcranial direct current stimulation (tDCS), an intervention known to decrease GABA. The magnitude of M1 GABA decrease induced by anodal tDCS correlated positively with both the degree of motor learning and the degree of fMRI signal change within the left M1 during learning. This study therefore suggests that the responsiveness of the GABAergic system to modification may be relevant to short-term motor learning behavior and learning-related brain activity.  相似文献   
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Nearly a third of all eukaryotic proteins are transported from the ER to the Golgi apparatus through the secretory pathway using COPII coated vesicles. Evidence suggests that this transport occurs via 500–900 Å vesicles that bud from the ER membrane. It has been shown that procollagen molecules utilize the COPII proteins for transport, but it is unclear how the COPII coat can accommodate these ~3000 Å long molecules. We now present a cryogenic electron tomographic reconstruction of a Sec13/31 tubule that is approximately 3300 Å long containing a hollow cylindrical interior that is 300 Å in diameter, dimensions that are consistent with those that are required to encapsulate a procollagen molecule wrapped in a membrane and accessory COPII components. This structure suggests a novel mechanism that the COPII coat may employ to transport elongated cargo.  相似文献   
6.
Apoflavodoxin from the sulfate reducing bacteria Desulfovibrio desulfuricans is a small, acidic protein with a net charge of -19 at neutral pH. Here, we show that monovalent cations in biologically relevant amounts have dramatic effects on apoflavodoxin stability. The effect is largest for Gdm(+) and decreases as a function of increased cation charge density (Gdm(+)>NH(4)(+)K(+) approximately Cs(+) approximately Na(+)>Li(+)). A linear correlation of stabilizing effects with cation hydration properties suggests an important role of dehydration in efficient cation interaction with the protein. The effects on stability are due to preferential binding of one cation to native apoflavodoxin and results in an increase in thermal midpoint of 20 degrees C and the free energy of unfolding (at 20 degrees C) increases fivefold. Tuning of biophysical properties (such as folding and ligand/cofactor binding) of acidic proteins by cation binding may be important in vivo.  相似文献   
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Summary The interactions between catecholamines and surfactants was investigated in perfused gills of the marine teleostPlatichthys flesus L. The activity of the branchial ion pumps was monitored via the electrogenic transepithelial potential (inside positive) measured in gills bathed and perfused with identical saline. Vascular resistance of the arterio-arterial and arterio-venous pathway was also recorded simultaneously by measuring respectively the afferent perfusion pressure and venous flow in gills perfused at constant flow and at constant efferent pressure. The specific effects of respective - and -adrenergic receptor stimulation was investigated by the administration of discrete doses of either adrenaline in the presence of 10 mol l–1 propranolol or isoprenaline in the perfusate. In the absence of surfactants the -adrenergic effects were an inhibition of electrogenic ion transport, a decrease in venous flow and an increase in the vascular resistance of the arterioarterial vascular pathway. In contrast the -adrenergic effects consisted of a stimulation of electrogenic ion transport and a vasodilation of the arterio-arterial pathway. Both anionic (linear alkyl sulphonate; sodium lauryl sulphate) and non-ionic (nonyl phenol ethoxylate; synthetic alcohol ethoxylate) surfactants were administered in the perfusate at nominal concentrations of 1 mol l–1 (0.3–0.5 mg l–1). None of these compounds had any effect on the affinity or the efficacy of the -adrenergic responses. In contrast there was a significant reduction in the efficacy of isoprenaline in the presence of all of the surfactants used but only in the case of the synthetic alcohol ethoxylate was there an effect on the affinity of this agonist for the -adrenergic receptor. The results are discussed in the context of the mechanism of action of these environmental contaminants and the nature of adrenergic receptors in the gill.  相似文献   
9.
Eight different isolates of Theileria parva and one isolate of T. taurotragi, in the form of intra-lymphocytic schizonts and/or purified piroplasms, were subjected to isoenzyme analysis for 24 enzymes by both isoelectric focusing in agarose and electrophoresis in starch gel. Twelve enzymes distinguished between T. parva and T. taurotragi; five enzymes (HK, GPI, PEP1, LDH and SOD) showed variations within T. parva. The metabolism of the host cell was affected by schizont infection, which masked intraspecific variations. Piroplasms were of more potential value for characterization of T. parva.  相似文献   
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