We investigate the excited state electronic structure of the model phase transition system In/Si(111) using femtosecond time- and angle-resolved photoemission spectroscopy (trARPES). An extreme ...ultraviolet 500 kHz laser source at 21.7 eV is utilized both to map the energy of excited states above the Fermi level and follow the momentum-resolved population dynamics on a femtosecond timescale. Excited-state band mapping is used to characterize the normally unoccupied electronic structure above the Fermi level in both structural phases of In/Si(111): the metallic (4 x 1) and the gapped (8 x 2) phases. The extracted band positions are compared withband-structure calculations utilizing density functional theory within both the local density approximation and GW approximations (single-particle Green's function (G) + screened Coulomb interaction (W)). While good overall agreement is found between the GW-calculated band structure and experiment, deviations in specific momentum regions may indicate the importance of excitonic effects not accounted for at this level of approximation. To probe the dynamics of these excited states, their momentum-resolved transient population dynamics are extracted with trARPES. The transient intensities are compared to a simulated spectral function modeled by a state population employing a transient elevated electronic temperature as determined experimentally. This allows the momentum-resolved population dynamics to be quantitatively reproduced, revealing important insights into the transfer of energy from the electronic system to the lattice. In particular, a comparison between the magnitude and relaxation time of the transient electronic temperature observed by trARPES with those of the lattice as probed in previous ultrafast electron diffraction studies implies a highly nonthermal phonon distribution at the surface following photo-excitation. This suggests that the energy from the initially excited electronic system is initially transferred to high-energy optical phonon modes followed by cooling and thermalization of the photo-excited system by much slower phonon-phonon coupling.
Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA) at type 1 DA receptors (D1Rs) are largely undefined. Here we show that tonic 5nM DA acts at D1Rs ...to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h). In the presence but not absence of 5nM DA, I h maximal conductance (G max) was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP), which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation). Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP's first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output.
Hybrid zones between closely related species or subspecies provide useful settings for studying the genetic architecture of speciation. Using markers distributed throughout the mouse genome, we use a ...hybrid zone between two recently diverged species of house mice (Mus musculus and Mus domesticus) as a natural mapping experiment to identify genomic regions that may be involved in reproductive isolation. Using cline analysis we document a nearly 50-fold variation in level of introgression among markers. Some markers have extremely narrow cline widths; these genomic regions may contribute to reproductive isolation. Biological processes associated with these narrow clines include physiological and immune responses to the environment as well as physiological and behavioral aspects of reproduction. Other autosomal markers exhibit asymmetrically broad clines, usually with high frequencies of M. domesticus alleles on the M. musculus side of the hybrid zone. These markers identify genome regions likely housing genes with alleles that are spreading from one species to the other. Biological processes associated with these wide clines include cell signaling, olfaction, and pheromone response. These processes play important roles in survival and reproduction, and associated genes are likely targets of selection. Patterns of linkage disequilibrium in the center of the hybrid zone suggest that isolation may be caused by multiple epistatic interactions between sets of genes. These data highlight the complex genetic architecture underlying speciation even at early stages of divergence and point to some of the biological processes that may govern this architecture.
Collective interaction of light with an atomic gas can give rise to superradiant instabilities. We experimentally study the sudden buildup of a reverse light field in a laser-driven high-finesse ring ...cavity filled with ultracold thermal or Bose-Einstein condensed atoms. While superradiant Rayleigh scattering from atomic clouds is normally observed only at very low temperatures (i.e., well below 1 microK), the presence of the ring cavity enhances cooperativity and allows for superradiance with thermal clouds as hot as several 10 microK. A characterization of the superradiance at various temperatures and cooperativity parameters allows us to link it to the collective atomic recoil laser.
The phases at which network neurons fire in rhythmic motor outputs are critically important for the proper generation of motor behaviors. The pyloric network in the crustacean stomatogastric ganglion ...generates a rhythmic motor output wherein neuronal phase relationships are remarkably invariant across individuals and throughout lifetimes. The mechanisms for maintaining these robust phase relationships over the long-term are not well described. Here we show that tonic nanomolar dopamine (DA) acts at type 1 DA receptors (D1Rs) to enable an activity-dependent mechanism that can contribute to phase maintenance in the lateral pyloric (LP) neuron. The LP displays continuous rhythmic bursting. The activity-dependent mechanism was triggered by a prolonged decrease in LP burst duration, and it generated a persistent increase in the maximal conductance (G(max)) of the LP hyperpolarization-activated current (I(h)), but only in the presence of steady-state DA. Interestingly, micromolar DA produces an LP phase advance accompanied by a decrease in LP burst duration that abolishes normal LP network function. During a 1 h application of micromolar DA, LP phase recovered over tens of minutes because, the activity-dependent mechanism enabled by steady-state DA was triggered by the micromolar DA-induced decrease in LP burst duration. Presumably, this mechanism restored normal LP network function. These data suggest steady-state DA may enable homeostatic mechanisms that maintain motor network output during protracted neuromodulation. This DA-enabled, activity-dependent mechanism to preserve phase may be broadly relevant, as diminished dopaminergic tone has recently been shown to reduce I(h) in rhythmically active neurons in the mammalian brain.
Neuromodulatory effects can vary with their mode of transmission. Phasic release produces local and transient increases in dopamine (DA) up to micromolar concentrations. Additionally, since DA is ...released from open synapses and reuptake mechanisms are not nearby, tonic nanomolar DA exists in the extracellular space. Do phasic and tonic transmissions similarly regulate voltage-dependent ionic conductances in a given neuron? It was previously shown that DA could immediately alter the transient potassium current (I(A)) of identified neurons in the stomatogastric ganglion of the spiny lobster Panulirus interruptus. Here we show that DA can also persistently alter I(A), and that the immediate and persistent effects of DA oppose one another. The lateral pyloric (LP) neuron exclusively expresses type 1 DA receptors (D1Rs). Micromolar DA produces immediate depolarizing shifts in the voltage dependence of LP I(A), whereas tonic nanomolar DA produces a persistent increase in LP I(A) maximal conductance (G(max)) through a translation-dependent mechanism involving target of rapamycin (TOR). The pyloric dilator (PD) neuron exclusively expresses D2Rs. Micromolar DA produces an immediate hyperpolarizing shift in PD I(A) voltage dependence of activation, whereas tonic DA persistently decreases PD I(A) G(max) through a translation-dependent mechanism not involving TOR. The persistent effects on I(A) G(max) do not depend on LP or PD activity. These data suggest a role for tonic modulators in the regulation of voltage-gated ion channel number; and furthermore, that dopaminergic systems may be organized to limit the amount of change they can impose on a circuit.
Dopamine (DA) modifies the motor pattern generated by the pyloric network in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus, by directly acting on each of the circuit ...neurons. The 14 pyloric neurons fall into six cell types, and DA actions are cell type specific. The transient potassium current mediated by shal channels (I(A)) is a common target of DA modulation in most cell types. DA shifts the voltage dependence of I(A) in opposing directions in pyloric dilator (PD) versus lateral pyloric (LP) neurons. The mechanism(s) underpinning cell-type specific DA modulation of I(A) is unknown. DA receptors (DARs) can be classified as type 1 (D1R) or type 2 (D2R). D1Rs and D2Rs are known to increase and decrease intracellular cAMP concentrations, respectively. We hypothesized that the opposing DA effects on PD and LP I(A) were due to differences in DAR expression patterns. In the present study, we found that LP expressed somatodendritic D1Rs that were concentrated near synapses but did not express D2Rs. Consistently, DA modulation of LP I(A) was mediated by a Gs-adenylyl cyclase-cAMP-protein kinase A pathway. Additionally, we defined antagonists for lobster D1Rs (flupenthixol) and D2Rs (metoclopramide) in a heterologous expression system and showed that DA modulation of LP I(A) was blocked by flupenthixol but not by metoclopramide. We previously showed that PD neurons express D2Rs, but not D1Rs, thus supporting the idea that cell specific effects of DA on I(A) are due to differences in receptor expression.
Male infertility affects ∼7% of men, but its causes remain poorly understood. The most severe form is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis. So far, ...only a few validated disease-associated genes have been reported. To address this gap, we performed whole-exome sequencing in 58 men with unexplained meiotic arrest and identified the same homozygous frameshift variant c.676dup (p.Trp226LeufsTer4) in M1AP, encoding meiosis 1 associated protein, in three unrelated men. This variant most likely results in a truncated protein as shown in vitro by heterologous expression of mutant M1AP. Next, we screened four large cohorts of infertile men and identified three additional individuals carrying homozygous c.676dup and three carrying combinations of this and other likely causal variants in M1AP. Moreover, a homozygous missense variant, c.1166C>T (p.Pro389Leu), segregated with infertility in five men from a consanguineous Turkish family. The common phenotype between all affected men was NOA, but occasionally spermatids and rarely a few spermatozoa in the semen were observed. A similar phenotype has been described for mice with disruption of M1ap. Collectively, these findings demonstrate that mutations in M1AP are a relatively frequent cause of autosomal recessive severe spermatogenic failure and male infertility with strong clinical validity.
Long-term intrinsic and synaptic plasticity must be coordinated to ensure stability and flexibility in neuronal circuits. Coordination might be achieved through shared transduction components. ...Dopamine (DA) is a well-established participant in many forms of long-term synaptic plasticity. Recent work indicates that DA is also involved in both activity-dependent and -independent forms of long-term intrinsic plasticity. We previously examined DA-enabled long-term intrinsic plasticity in a single identified neuron. The lateral pyloric (LP) neuron is a component of the pyloric network in the crustacean stomatogastric nervous system (STNS). LP expresses type 1 DA receptors (D1Rs). A 1 h bath application of 5 nM DA followed by washout produced a significant increase in the maximal conductance (G max) of the LP transient potassium current (I A) that peaked ~4 h after the start of DA application; furthermore, if a change in neuronal activity accompanied the DA application, then a persistent increase in the LP hyperpolarization activated current (I h) was also observed. Here, we repeated these experiments with pharmacological and peptide inhibitors to determine the cellular processes and signaling proteins involved. We discovered that the persistent, DA-induced activity-independent (I A) and activity-dependent (I h) changes in ionic conductances depended upon many of the same elements that enable long-term synaptic plasticity, including: the D1R-protein kinase A (PKA) axis, RNA polymerase II transcription, RNA interference (RNAi), and mechanistic target of rapamycin (mTOR)-dependent translation. We interpret the data to mean that increasing the tonic DA concentration enhances expression of a microRNA(s) (miRs), resulting in increased cap-dependent translation of an unidentified protein(s).
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