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1.
The heritability ( h2) of fitness traits is often low. Although this has been attributed to directional selection having eroded genetic variation in direct proportion to the strength of selection, heritability does not necessarily reflect a trait's additive genetic variance and evolutionary potential (“evolvability”). Recent studies suggest that the low h2 of fitness traits in wild populations is caused not by a paucity of additive genetic variance (V A) but by greater environmental or nonadditive genetic variance (V R). We examined the relationship between h2 and variance‐standardized selection intensities ( i or β σ), and between evolvability (I A:V A divided by squared phenotypic trait mean) and mean‐standardized selection gradients (β μ). Using 24 years of data from an island population of Savannah sparrows, we show that, across diverse traits, h2 declines with the strength of selection, whereas I A and I R (V R divided by squared trait mean) are independent of the strength of selection. Within trait types (morphological, reproductive, life‐history), h2, I A, and I R are all independent of the strength of selection. This indicates that certain traits have low heritability because of increased residual variance due to the age at which they are expressed or the multiple factors influencing their expression, rather than their association with fitness. 相似文献
2.
Voltage-gated potassium (KV) currents, subdivided into rapidly inactivating A-type currents (I
A) and slowly inactivating delayed rectifier currents (I
K), play a fundamental role in modulating pain by controlling neuronal excitability. The effects of Honokiol (Hon), a natural biphenolic compound derived from Magnolia officinalis, on KV currents were investigated in freshly isolated mouse dorsal root ganglion neurons using the whole-cell patch clamp technique. Results showed that Hon inhibited I
A and I
K in concentration-dependent manner. The IC50 values for block of I
A and I
K were 30.5 and 25.7 µM, respectively. Hon (30 µM) shifted the steady-state activation curves of I
A and I
K to positive potentials by 17.6 and 16.7 mV, whereas inactivation and recovery from the inactivated state of I
A were unaffected. These results suggest that Hon preferentially interacts with the active states of the I
A and I
K channels, and has no effect on the resting state and inactivated state of the I
A channel. Blockade on K+ channels by Hon may contribute to its antinociceptive effect, especially anti-inflammatory pain. 相似文献
3.
Previously, we reported that apoptosis of cerebellar granular neurons induced by low‐K + and serum‐free (LK‐S) was associated with an increase in the A‐type K + channel current ( IA), and an elevated expression of main α‐subunit of the IA channel, which is known as Kv4.2 and Kv4.3. Here, we show, as assessed by quantitative RT‐PCR and whole‐cell recording, that besides Kv4.2 and Kv4.3, Kv1.1 is very important for IA channel. The expression of Kv1.1 was elevated in the apoptotic neurons, while silencing Kv1.1 expression by siRNA reduced the IA amplitude of the apoptotic neuron, and increased neuron viability. Inhibiting Kv1.1 current by dendrotoxin‐K evoked a similar effect of reduction of IA amplitude and protection of neurons. Applying a protein kinase C (PKC) activator, phorbol ester acetate A (PMA) mimicked the LK‐S‐induced neuronal apoptotic effect, enhanced the IA amplitude and reduced the granule cell viability. The PKC inhibitor, bisindolylmaleimide I and Gö6976 protected the cell against apoptosis induced by LK‐S. After silencing the Kv1.1 gene, the effect of PMA on the residual K + current was reduced significantly. Quantitative RT‐PCR and Western immunoblot techniques revealed that LK‐S treatment and PMA increased the level of the expression of Kv1.1, in contrast, bisindolylmaleimide I inhibited Kv1.1 expression. In addition, the activation of the PKC isoform was identified in apoptotic neurons. We thus conclude that in the rat cerebellar granule cell, the IA channel associated with apoptotic neurons is encoded mainly by the Kv1.1 gene, and that the PKC pathway promotes neuronal apoptosis by a brief modulation of the IA amplitude and a permanent increase in the levels of expression of the Kv1.1 α‐subunit. 相似文献
4.
Azolla, a small water fern, abscises its roots and branches within 30 min upon treatment with various stresses. This study was conducted to test whether, in the rapid abscission that occurs in Azolla, breakdown of wall components of abscission zone cells by ●OH is involved. Experimentally generated ●OH caused the rapid separation of abscission zone cells from detached roots and the rapid shedding of roots from whole plants. Electron microscopic observations revealed that ●OH rapidly and selectively dissolved a well‐developed middle lamella between abscission zone cells and resultantly caused rapid cell separation and shedding. Treatment of abscission zones of Impatiens leaf petiole with ●OH also accelerated the separation of abscission zone cells. However, compared with that of Azolla roots, accelerative effects in Impatiens were weak. A large amount of ●OH was cytochemically detected in abscission zone cells both of Azolla roots and of Impatiens leaf petioles. These results suggest that ●OH is involved in the cell separation process not only in the rapid abscission in Azolla but also in the abscission of Impatiens. However, for rapid abscission to occur, a well‐developed middle lamella, a unique structure, which is sensitive to the attack of ●OH, might be needed. 相似文献
5.
We developed a multicompartmental Hodgkin-Huxley model of the Hermissenda type-B photoreceptor and used it to address the relative contributions of reductions of two K + currents, I
a and I
C, to changes in cellular excitability and synaptic strength that occur in these cells after associative learning. We found that reductions of g C, the peak conductance of I
C, substantially increased the firing frequency of the type-B cell during the plateau phase of a simulated light response, whereas reductions of g A had only a modest contribution to the plateau frequency. This can be understood at least in part by the contributions of these currents to the light-induced (nonspiking) generator potential, the plateau of which was enhanced by g C reductions, but not by g A reductions. In contrast, however, reductions of g A broadened the type-B cell action potential, increased Ca 2+ influx, and increased the size of the postsynaptic potential produced in a type-A cell, whereas similar reductions of g C had only negligible contributions to these measures. These results suggest that reductions of I
A and I
C play important but different roles in type-B cell plasticity. 相似文献
6.
The modulation of I
A
K + current by ten trivalent lanthanide (Ln 3+) cations spanning the series with ionic radii ranging from 0.99 ? to 1.14 ? was characterized by the whole-cell patch clamp
technique in bovine adrenal zona fasciculata (AZF) cells. Each of the ten Ln 3+s reduced I
A
amplitude measured at +20 mV in a concentration-dependent manner. Smaller Ln 3+s were the most potent and half-maximally effective concentrations (EC 50s) varied inversely with ionic radius for the larger elements. Estimation of EC 50s yielded the following potency sequence: Lu 3+ (EC 50= 3.0 μ m) ≈ Yb 3+ (EC 50= 2.7 μ m) > Er 3+ (EC 50= 3.7 μ m) ≥ Dy 3+ (EC 50= 4.7 μ m) > Gd 3+ (EC 50= 6.7 μ m) ≈ Sm 3+ (EC 50= 6.9 μ m) > Nd 3+ (EC 50= 11.2 μ m) > Pr 3+ (EC 50= 22.3 μ m) > Ce 3+ (EC 50= 28.0 μ m) > La 3+ (EC 50= 33.7 μ m).
Ln 3+s altered selected voltage-dependent gating and kinetic parameters of I
A
with a potency and order of effectiveness that paralleled the reduction of I
A
amplitude. Ln 3+s markedly slowed activation kinetics and shifted the voltage-dependence of I
A
gating such that activation and steady-state inactivation occurred at more depolarized potentials. In contrast, Ln 3+s did not measurably alter inactivation or deactivation kinetics and only slightly slowed kinetics of inactivated channels
returning to the closed state. Replacement of external Ca 2+ with Mg 2+ had no effect on the concentration-dependent inhibition of I
A
by Ln 3+s. In contrast to their action on I
A
K + current, Ln 3+s inhibited T-type Ca 2+ currents in AZF cells without slowing activation kinetics.
These results indicate that Ln 3+ modulate I
A
K + channels through binding to a site on I
A
channels located within the electric field but which is not specific for Ca 2+. They are consistent with a model where Ln 3+ binding to negative charges on the gating apparatus alters the voltage-dependence and kinetics of channel opening. Ln 3+s modulate transient K + and Ca 2+ currents by two fundamentally different mechanisms.
Received: 21 January 1997/Revised: 3 April 1998 相似文献
7.
Summary Although an outwardly rectifying K +-conductance has been described in murine peritoneal macrophages and a murine macrophage cell line, the expression of this conductance in human monocyte-derived macrophages (HMDMs) is rare. Whole-cell current recordings in this study were obtained from HMDMs differentiated in adherent culture for varying periods of time following isolation and compared to currents obtained in human alveolar macrophages (HAMs) obtained from bronchoalveolar lavage. These studies were undertaken to compare ionic current expression in the in vitro differentiated macrophage to that of a human tissue macrophage. HAMs are the major population of immune and inflammatory cells in the normal lung and are the most readily available source of human tissue macrophages. Of the 974 HMDMs in the study obtained from a total of 36 donors, we were able to observe the presence of the inactivating outward current ( I
A
) which exhibited voltage-dependent availability in only 49 (or 5%) of the cells. In contrast, whole-cell current recordings from HAMs, revealed a significantly higher frequency of I
A
expression (50% in a total of 160 cells from 26 donors). In the alveolar cell, there was no correlation observed between cell size and peak I
A
amplitude, nor was there a relationship between peak I
A
amplitude and time in culture. The current in both cell types was K + selective and 4-aminopyridine (4-AP) sensitive. I
A
in both cell types inactivated with a time course which was weakly voltage-dependent and which exhibited a time constant of recovery from inactivation of approximately 30 sec. The time course of current inactivation was dependent upon the external K + concentration. An increase in the time constant describing current decay was observed in elevated K +. Current activation was half-maximal at approximately –18 mV in normal bathing solution. Steady-state inactivation was half-maximal at approximately –44 mV. The presence of the outwardly rectifying K + conductance may alter the potential of the mononuclear phagocyte to respond to extracellular signals mediating chemotaxis, phagocytosis, and tumoricidal functions. 相似文献
8.
Pavlovian conditioning in Hermissenda produces a decrease in voltage-dependent (I K,A and I Ca) and Ca 2+-dependent (I K,Ca) currents, and an increase in the action potential (AP) duration in type B-photoreceptors. In addition, synaptic connections between B and A photoreceptors and B photoreceptor and type I interneurons are facilitated. The increase in AP duration, produced by decreasing one or more K + currents, may account for synaptic facilitation. The present study examined this issue by using a mathematical model of the B-photoreceptor and the neurosimulator SNNAP. In the model, decreasing g K,A by 70% increased the duration of the AP in the terminal by 41% and Ca 2+ influx by 30%. However, if the decrease in g K,A was combined with a decrease in g Ca, similar to what has been reported experimentally, the Ca 2+ influx decreased by 54%. Therefore, the concomitant change in I Ca counter-acted the broadening-induced increase in Ca 2+ influx in the synaptic terminal. This result suggests that a spike-duration independent process must contribute to the synaptic facilitation observed following Pavlovian conditioning. 相似文献
9.
The effect of adenosine regulation on sodium and chloride transport was examined in cultured A 6 renal epithelial cells. Adenosine and its analogue N 6-cyclopentyladenosine (CPA) had different effects on short-circuit current ( I
sc) depending on the side of addition. Basolateral CPA addition induced an approximately threefold increase of the I
sc that reached a maximum effect 20 min after addition and was completely inhibited by preincubation with either an A 2 selective antagonist, CSC, or the sodium channel blocker, amiloride. Apical CPA addition induced a biphasic I
sc response characterized by a rapid fourfold transient increase over its baseline followed by a decline and a plateau phase
that were amiloride insensitive. The A 1 adenosine antagonist, CPX, completely prevented this response. This I
sc response to apical CPA was also strongly reduced in Cl −-free media and was significantly inhibited either by basolateral bumetanide or apical DPC preincubation. Only basolateral
CPA addition was able to induce an increase in cAMP level. CPA, added to cells in suspension, caused a rapid rise in [Ca 2+]
i
that was antagonized by CPX, not affected by CSC and prevented by thapsigargin preincubation. These data suggest that basolateral
CPA regulates active sodium transport via A 2 adenosine receptors stimulating adenylate cyclase while apical CPA regulates Cl − secretion via A 1 receptor-mediated changes in [Ca 2+]
i
. 相似文献
10.
The use of relative variable fluorescence (RVF) of chlorophyll, as measured in the presence of Diuron, an inhibitor of electron transfer, for the estimation of the photosynthetic activity of plankton microalgae was analyzed under a wide range of light intensities in the PAR region. Oxygen evolution rates (estimated by the method of light and dark bottles and the amperometric method), RVF, and chlorophyll a concentration were measured in parallel in natural algal cenoses and microecosystems. When the previously used regression equation, in the form A = b( F/ F
d) C
chl
I, where A is O 2 evolution rate (g/(m 3 h), F/ F
d is RVF (relative units), C
chl is chlorophyll a concentration (mg/m 3), and I is light intensity (W/m 2), was verified in the PAR region, we observed a nonlinear dependence of the correction coefficient b on I, which can be described by the formula b = 6.227 × 10 3I. This result agrees with the hypothesis that chlorophyll a fluorescence quenching comprises photochemical ( qQ) and energy ( qE) components. On the basis of the energy model, we determined the upper limit b
max = 0.003 for light intensity range I< 4.4 W/m 2 and the lower limit b
min = 0.0003 for I = 400 W/m 2. 相似文献
11.
Dopamine (DA) released from the hypothalamus tonically inhibits pituitary lactotrophs. DA (at micromolar concentration) opens
potassium channels, hyperpolarizing the lactotrophs and thus preventing the calcium influx that triggers prolactin hormone
release. Surprisingly, at concentrations ∼1000 lower, DA can stimulate prolactin secretion. Here, we investigated whether
an increase in a K + current could mediate this stimulatory effect. We considered the fast K + currents flowing through large-conductance BK channels and through A-type channels. We developed a minimal lactotroph model
to investigate the effects of these two currents. Both I
BK and I
A could transform the electrical pattern of activity from spiking to bursting, but through distinct mechanisms. I
BK always increased the intracellular Ca 2+ concentration, while I
A could either increase or decrease it. Thus, the stimulatory effects of DA could be mediated by a fast K + conductance which converts tonically spiking cells to bursters. In addition, the study illustrates that a heterogeneous distribution
of fast K + conductances could cause heterogeneous lactotroph firing patterns.
Action Editor: Christiane Linster 相似文献
12.
Measurements of Δ I as a function of retinal area illuminated have been obtained at various levels of standard intensity I
1, using "white" light and light of three modal wave-lengths (λ465, 525, 680), for monocular stimulation and for simultaneous excitation of the two eyes ("binocular"), using several methods of varying (rectangular) area and retinal location, with control of exposure time. For data homogeneous with respect to method of presentation, log Δ Im = -Z log A + C, where Δ I = Ĩ
2 – I
1, A is area illuminated, and C is a terminal constant (= log Δ Im for A = 1 unit) depending on the units in which Δ I and A are expressed, and upon I
1. The equation is readily deduced on dimensional grounds, without reference to specific theories of the nature of Δ I or of retinal area in terms of its excitable units. Z is independent of the units of I and A. Experimentally it is found to be the same for monocular and binocular excitations, as is to be expected. Also as is expected it is not independent of λ, and it is markedly influenced by the scheme according to which A is varied; it depends directly upon the rate at which potentially excitable elements are added when A is made to increase. For simultaneous excitation of the two eyes (when of very nearly equivalent excitability), Δ ĪB is less than for stimulation of either eye alone, at all levels of I
1, A, λ. The mean ratio (Δ ĪL + Δ ĪR)/2 to Δ IB was 1.38. For white light, doubling A on one retina reduces Δ Im in the ratio 1.21, or a little less than for binocular presentation under the same conditions. These facts are consistent with the view that the properties of Δ I are quantitatively determined by events central to the retina. The measure σ 1ΔI of organic variation in discrimination of intensities and Δ Im are found to be in simple proportion, independent of I
1, A, λ (and exposure time). Variability (σ 1ΔI) is not a function of the mode of presentation, save that it may be slightly higher when both retinas are excited, and its magnitude (for a given level of Δ Im) is independent of the law according to which the adjustable intensity I
2 is instrumentally controlled. 相似文献
13.
Neurofibrillary pathology of abnormally hyperphosphorylated Tau is a key lesion of Alzheimer disease and other tauopathies, and its density in the brain directly correlates with dementia. The phosphorylation of Tau is regulated by protein phosphatase 2A, which in turn is regulated by inhibitor 2, I 2PP2A. In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I 2PP2A is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I 2NTF) and the C-terminal fragment (I 2CTF). Both I 2NTF and I 2CTF are known to bind to the catalytic subunit of protein phosphatase 2A and inhibit its activity. Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I 2PP2A translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I 2PP2A, except when I 2PP2A was mutated at the cleavage site Asn-175 to Gln. Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I 2PP2A, inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I 2PP2A-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target. 相似文献
14.
Serotonin (5-HT) applied to the exposed but otherwise intact nervous system results in enhanced excitability of Hermissenda type-B photoreceptors. Several ion currents in the type-B photoreceptors are modulated by 5-HT, including the A-type K + current (I K,A), sustained Ca 2+ current (I Ca,S), Ca-dependent K + current (I K,Ca), and a hyperpolarization-activated inward rectifier current (I h). In this study, we developed a computational model that reproduces physiological characteristics of type B photoreceptors, e.g. resting membrane potential, dark-adapted spike activity, spike width, and the amplitude difference between somatic and axonal spikes. We then used the model to investigate the contribution of different ion currents modulated by 5-HT to the magnitudes of enhanced excitability produced by 5-HT. Ion currents were systematically varied within limits observed experimentally, both individually and in combinations. A reduction of I K,A or I K,Ca, or an increase in I h enhanced excitability by 20–50%. Decreasing I Ca,S produced a dramatic decrease in excitability. Reductions of I K,V produced only minimal increases in excitability, suggesting that I K,V probably plays a minor role in 5-HT induced enhanced excitability. Combinations of changes in I K,A, I K,Ca, I h and I Ca,S produced increases in excitability comparable to experimental observations. After 5-HT application, the cell's depolarization force is shifted from the I h–I Ca,S combination to predominantly I h. 相似文献
15.
In Hermissenda type-B photoreceptors, the spike is generated in the axon and back-propagated to the soma, resulting in smaller somatic spikes.
Experimentally, blocking the A-type K + current ( IK,A) results in broadening of somatic spikes. Similarly, in a compartmental model of the photoreceptor, reducing the maximum
A-type K + conductance ( gK,Amax) results in broadening of somatic spikes. However, simulations predict that little or no broadening of axonal spikes occurs
when gK,Amax is reduced. The results can be explained by the voltage-dependent properties of IK,A and the different potential ranges that the somatic and axonal spike traverse. Because of the steeper I-V curve and faster activation of the K + channels at higher potentials, the recruitment of additional K + channels in the axon is able to compensate for the decrease in K + conductance, yielding less spike broadening. These results also support the idea that spike duration in the axon may not
be reliably inferred based upon recordings collected from the soma.
Action Editor: Jonathan D. Victor 相似文献
16.
A modified version of capillary isoelectric focusing (cIEF) was developed to separate hemoglobin variants contained within single human erythrocytes. Laser-induced native fluorescence with 275 nm excitation was used to detect the separated hemoglobins. In this method, baseline fluctuations were minimized and detection sensitivity was improved by using dilute solutions of anolyte, catholyte, and carrier ampholytes (with methylcellulose). Since electrosmotic flow was used for mobilization of the focused bands, separation and detection were integrated into a single step. The capillary was first filled with only ampholyte solution, and the cell (or standard) was injected as in capillary zone electrophoresis. The ∼90 fl injection volume for individual cells is 7×10 4 times lower than those previously reported. Adult (normal and elevated A 1), sickle (heterozygous), and fetal erythrocytes were analyzed, with the amounts of hemoglobins A 0, A 1c, S and F determined. The pH gradient for cIEF was linear ( r2 = 0.9984), which allowed tentative identification of Hb F ac. Variants differing by as little as 0.025 p I units were resolved. 相似文献
17.
The effects of sodium metabisulfite (SMB), a general food preservative, on potassium currents in rat dorsal root ganglion
(DRG) neurons were investigated using the whole-cell patch-clamp technique. SMB increased the amplitudes of both transient
outward potassium currents and delayed rectifier potassium current in concentration- and voltage-dependent manner. The transient
outward potassium currents (TOCs) include a fast inactivating (A-current or I
A) current and a slow inactivating (D-current or I
D) current. SMB majorly increased I A, and I D was little affected. SMB did not affect the activation process of transient outward currents (TOCs), but the inactivation
curve of TOCs was shifted to more positive potentials. The inactivation time constants of TOCs were also increased by SMB.
For delayed rectifier potassium current ( I
K), SMB shifted the activation curve to hyperpolarizing direction. SMB differently affected TOCs and I
K, its effects major on A-type K + channels, which play a role in adjusting pain sensitivity in response to peripheral redox conditions. SMB did not increase
TOCs and I
K when adding DTT in pipette solution. These results suggested that SMB might oxidize potassium channels, which relate to adjusting
pain sensitivity in pain-sensing DRG neurons. 相似文献
18.
A purified peptide from Androctonus australis Garzoni venom (AaG) affects selectively a K +-current recorded from cerebellum granular cells. This current is characterized by fast activating and inactivating kinetics
similar to an I A-type current. Addition of 2 μ m peptide Aa1 (from Androctonus australis, toxin 1) to the external side of the channel suppressed completely and in a selective manner the I A-type current, with an IC50 value of 130 n m, whereas in the same conditions, the other potassium current, identified as delayed rectifier (I d), was not affected. Additionally, we show that another partially purified peptide (III-12) from the same venom was able to
block reversibly both K +-currents.
Received: 10 February 1997 / Accepted: 7 August 1997 相似文献
19.
The preparation and characterization of α-L -glutamic acid oligomers with degree of polymerization (DP) up to 12 are described. The preparation of polymers with low DP corresponding to various A/ I ratios (where A and I are monomer and initiator concentrations, respectively) with end groups blocked is given. The conditions of the fractionation, which separates the different oligomers by ion-exchange chromatography, are discussed. Finally, the isolation from salt solutions of the pure acidic form is given. Each polymer obtained for a given A/ I is characterized at the end of the polymerization by its molecular-weight distribution. The average DP values calculated are compared to the A/ I values; agreement is very good. Potentiometric behaviour during neutralization is obtained as a function of the degree of polymerization and the elaboration of the polyelectrolytic phenomenon is discussed. 相似文献
20.
A laboratory upflow anaerobic sludge blanket reactor, seeded with fine, suspended, bacterial floc with 1.76 g volatile suspended solids/l, was used to treat synthetic methanolic waste. After 180 days of continuous peration, granular sludge with discrete granules of 1 to 2 mm diam. was formed, with 52 g volatile suspended solids/l. Granules were brown, relatively soft and had a settling velocity of 1.61 cm/s. Extracellular polymeric matter extracted from the granular sludge had high carbohydrate content but low nucleic acid content. The ash of the granular sludge contained Na +, K + and Mg 2+ up to 15.0, 11.7 and 3.75 mg/g, respectively. Scanning and transmission electron microscopy revealed that the granular sludge was dominated by methanogens resembling Methanosarcina.The authors are with the Department of Environmental Engineering, Faculty of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565, Japan 相似文献
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