Nearby Nucleus Research Articles

High Frequency Electrical Stimulation of Lateral Habenula Reduces Voluntary Ethanol Consumption in Rats.

Background:Development of new strategies that can effectively prevent and/or treat alcohol use disorders is of paramount importance, because the currently available treatments are inadequate. Increasing evidence indicates that the lateral habenula (LHb) plays an important role in aversion, drug abuse, and depression. In light of the success of high-frequency stimulation (HFS) of the LHb in improving helplessness behavior in rodents, we assessed the effects of LHb HFS on ethanol-drinking behavior in rats.Methods:We trained rats to drink ethanol under an intermittent access two-bottle choice procedure. We used c-Fos immunohistochemistry and electrophysiological approaches to examine LHb activity. We applied a HFS protocol that has proven effective for reducing helplessness behavior in rats via a bipolar electrode implanted into the LHb.Results:c-Fos protein expression and the frequency of both spontaneous action potential firings and spontaneous excitatory postsynaptic currents were higher in LHb neurons of ethanol-withdrawn rats compared to their ethanol-naïve counterparts. HFS to the LHb produced long-term reduction of intake and preference for ethanol, without altering locomotor activity. Conversely, low-frequency electrical stimulation to the LHb or HFS applied to the nearby nucleus did not affect drinking behavior.Conclusions:Our results suggest that withdrawal from chronic ethanol exposure increases glutamate release and the activity of LHb neurons, and that functional inhibition of the LHb via HFS reduces ethanol consumption. Thus, LHb HFS could be a potential new therapeutic option for alcoholics.

ALMA 0.1–0.2 arcsec RESOLUTION IMAGING OF THE NGC 1068 NUCLEUS: COMPACT DENSE MOLECULAR GAS EMISSION AT THE PUTATIVE AGN LOCATION

ABSTRACT We present the results of our ALMA Cycle 2 high angular resolution (0.″1–0.″2) observations of the nuclear region of the nearby well-studied type-2 active galactic nucleus (AGN), NGC 1068, at HCN J = 3–2 and HCO+ J = 3–2 emission lines. For the first time, due to a higher angular resolution than previous studies, we clearly detected dense molecular gas emission at the putative AGN location, identified as a ∼1.1 mm (∼266 GHz) continuum emission peak, by separating this emission from brighter emission located at 0.″5–2.″0 on the eastern and western sides of the AGN. The estimated intrinsic molecular emission size and dense molecular mass, which are thought to be associated with the putative dusty molecular torus around an AGN, were ∼10 pc and ∼several × 105 M ⊙, respectively. HCN-to-HCO+ J = 3–2 flux ratios substantially higher than unity were found throughout the nuclear region of NGC 1068. The continuum emission displayed an elongated morphology along the direction of the radio jet located at the northern side of the AGN, as well as a weak spatially-resolved component at ∼2.″0 on the southwestern side of the AGN. The latter component most likely originated from star formation, with the estimated luminosity more than one order of magnitude lower than the luminosity of the central AGN. No vibrationally excited (v 2 = 1f) J = 3–2 emission lines were detected for HCN and HCO+ across the field of view.

Benchmarking mean-field approximations to level densities

We assess the accuracy of finite-temperature mean-field theory using as a standard the Hamiltonian and model space of the shell model Monte Carlo calculations. Two examples are considered: the nucleus $^{162}$Dy, representing a heavy deformed nucleus, and $^{148}$Sm, representing a nearby heavy spherical nucleus with strong pairing correlations. The errors inherent in the finite-temperature Hartree-Fock and Hartree-Fock-Bogoliubov approximations are analyzed by comparing the entropies of the grand canonical and canonical ensembles, as well as the level density at the neutron resonance threshold, with shell model Monte Carlo (SMMC) calculations, which are accurate up to well-controlled statistical errors. The main weak points in the mean-field treatments are seen to be: (i) the extraction of number-projected densities from the grand canonical ensembles, and (ii) the symmetry breaking by deformation or by the pairing condensate. In the absence of a pairing condensate, we confirm that the usual saddle-point approximation to extract the number-projected densities is not a significant source of error compared to other errors inherent to the mean-field theory. We also present an alternative formulation of the saddle-point approximation that makes direct use of an approximate particle-number projection and avoids computing the usual three-dimensional Jacobian of the saddle-point integration. We find that the pairing condensate is less amenable to approximate particle-number projection methods due to the explicit violation of particle-number conservation in the pairing condensate. Nevertheless, the Hartree-Fock-Bogoliubov theory is accurate to less than one unit of entropy for $^{148}$Sm at the neutron threshold energy, which is above the pairing phase transition.

Discrete knot ejection from the jet in a nearby low-luminosity active galactic nucleus, M81∗

Observational constraints of relativistic jets from black holes has largely come from the most powerful and extended jets\cite{Jorstad05,Asada14}, leaving the nature of the low luminosity jets a mystery\cite{Falcke04}. M81* is one of the nearest low-luminosity jets, which underwent an extremely large radio flare in 2011, allowing us to study compact core emission with unprecedented sensitivity and linear resolution. Utilizing a multi-wavelength campaign, we were able to track the flare as it re-brightened and became optically thick. Simultaneous X-ray observations indicated the radio re-brightening was preceded by a low energy X-ray flare at least $t_{\rm delay}>12\ {\rm days}$ prior. Associating the time delay between the two bands as the cooling time in a synchrotron flare\cite{Urry97,Bai03}, we find the magnetic field strength was $1.9<B<9.2\ {\rm G}$, which is consistent with magnetic field estimate from spectral-energy distribution modeling\cite{Kellerman81}, $B<10.2\ {\rm G}$. In addition, VLBA observations at 23 GHz clearly illustrate a discrete knot moving mildly relativistically at $v_{\rm app}/c=0.51\pm0.17$ associated with the initial radio flare. The observations indicate radial jet motions for the first time in M81*. This has profound implications for jet production, as it means radial motion can be observed in even the lowest-luminosity AGN, but at slower velocities and smaller radial extents ($\approx10^4\ R_{\rm G}$).

ESR Study of K-Mo&lt;sub&gt;2&lt;/sub&gt;C for Increased Catalytic Properties

The presence of potassium in molybdenum carbide morphology has been reported to increase the selectivity and reactivity of its catalytic properties. Potassium with its tendency to donate electron will enhance the electron density at the surface of catalyst by donating its electron at the vacant orbital framework either to carbon or metal moiety. This phenomenon will cause temporary paramagnetic properties of the catalyst and can be easily detected using an ESR spectrometer. In this paper, an ESR-based study to identify and prove that donating electron does take place at Mo2C after being promoted with potassium was conducted. Introduction of H2 and UV radiation were also carried out for comparison.The result from ESR spectra showed that in the absence of potassium in the Mo2C, no ESR signal was observed. However, in the presence of potassium, a singlet peak with g value ca. 1.9723 was found. The presence of a single peak indicated that the donated electron did not interact with any nearby nucleus in the surroundings. Deviation value of 2.0023 for free electron, indicates that this donated an electron probably interacted with an empty 4d orbital from molybdenum or 2p orbital from carbon.In the introduction of H2 gas and UV radiation, the finding showed that an increasing trend of singlet peak in the ESR spectrum earlier was observed. The trend indicated that the splitting of H2 by UV radiation generated new electron and joined the donated electron from K circulating at the surface of K-Mo2C morphology without interacting with another nucleus.

Electron paramagnetic resonance study of free radicals in γ-irradiated L-glutamine and L-glutamine-t-butyl ester hydrochloride

Electron paramagnetic resonance (EPR) spectra of γ-irradiated single crystals of l-glutamine (LG) and l-glutamine-t-butyl ester hydrochloride (LGBESHCI) powders were studied and analyzed for different orientations of the crystals in the magnetic field, after γ-irradiation. The spectra were observed to be independent of temperature down to 130 K. The hyperfine interaction tensors for one α proton and two β protons of radical have been determined at 295 K. An analysis of the EPR of γ-irradiated single crystals of LG and LGBESHCI powders shows that the paramagnetic species produced by the radiation damage is CH2ĊH. The g values of the radical and the hyperfine structure constants of the free electron with nearby protons and 14N nucleus were determined. The results were found to be in good agreement with the existing literature data.

Probing the Secondary Structure of Membrane Proteins with the Pulsed EPR Technique: Electron Spin Ehco Envelope Modulation (ESEEM)

Despite the importance and large number of membrane proteins, relatively limited structural information is known about them. New biophysical techniques are needed to probe their structural properties. Their hydrophobic nature and low expression yields cause difficulties for traditional structural techniques such as x-ray crystallography and solution NMR. ESEEM spectroscopy indirectly observes NMR transitions through an electron spin coupled to a nearby NMR active nucleus. ESEEM can detect weak dipolar interactions between a NMR active nucleus and a spin label out to a distance of approximately 8 Å. The modulation depth for weakly coupled nuclei is scaled by 1/r6. A novel approach is being developed to probe the secondary structure of membrane proteins and peptides qualitatively utilizing the three-pulse Electron Spin Echo Envelope Modulation (ESEEM) pulse sequence. In order to demonstrate the practicality of this biophysical technique, the M2delta subunit of AChR (α-helical) and KIGAKI(β-sheet) peptides were incorporated into phospholipids bicelle to probe their secondary structure with ESSEM spectroscopy. Utilizing site-directed spin-labeling (SDSL) coupled with deuterated amino acid labeling of the peptides, the corresponding ESEEM spectra reveal characteristic patterns for α-helix and β-sheet structures. This ESSEM secondary structural approach can be used with different deuterated amino acids and provide pertinent qualitative structural information on membrane proteins in a short period of time (10 minutes) with small amounts of sample (30 µg).

The nucleus is an intracellular propagator of tensile forces in NIH 3T3 fibroblasts.

Nuclear positioning is a crucial cell function, but how a migrating cell positions its nucleus is not understood. Using traction-force microscopy, we found that the position of the nucleus in migrating fibroblasts closely coincided with the center point of the traction-force balance, called the point of maximum tension (PMT). Positioning of the nucleus close to the PMT required nucleus-cytoskeleton connections through linker of nucleoskeleton-to-cytoskeleton (LINC) complexes. Although the nucleus briefly lagged behind the PMT following spontaneous detachment of the uropod during migration, the nucleus quickly repositioned to the PMT within a few minutes. Moreover, traction-generating spontaneous protrusions deformed the nearby nucleus surface to pull the nuclear centroid toward the new PMT, and subsequent retraction of these protrusions relaxed the nuclear deformation and restored the nucleus to its original position. We propose that the protruding or retracting cell boundary transmits a force to the surface of the nucleus through the intervening cytoskeletal network connected by the LINC complexes, and that these forces help to position the nucleus centrally and allow the nucleus to efficiently propagate traction forces across the length of the cell during migration.

Improved cisplatin delivery in cervical cancer cells by utilizing folate-grafted non-aggregated gelatin nanoparticles

PurposeCisplatin is highly effective in the treatment of cervical cancer. However, in therapeutic doses, cisplatin induces several adverse effects due to undesirable tissue distribution. Therefore, it is worth targeting cisplatin in cervical cancer cells by implicating non-aggregated ligand-modified nanotherapeutics. Methods and resultsHere, we report the preparation of non-aggregated folic acid-conjugated gelatin nanoparticles of cisplatin (Cis-GNs-FA) by two-step desolvation method with mean particle size of 210.6±9.6nm and 140.5±10.9nm for Cis-GNs to improve the drug delivery in cervical cancer, HeLa cells. FTIR and DSC spectra confirmed the presence and stability of cisplatin in gelatin matrix. Furthermore, amorphization of cisplatin in nanoparticles was ascertained by PXRD. Drug release followed a first-order release kinetic at both pH ∼ 5.6 (cervical cancer pH) and pH ∼ 7.4. In addition, a significant (P<0.05) decrease in IC50 value (8.3μM) and enhanced apoptosis were observed in HeLa cells treated with Cis-GNs-FA as compared to Cis-GNs (15.1μM) and cisplatin solution (40.2μM). In contrast, A549 lung cancer cells did not discriminate between Cis-GNs-FA and Cis-GNs due to the absence of folate receptors-α (FR-α). Consistently, higher cellular uptake, 80.54±7.60% was promoted by Cis-GNs-FA significantly (two-way ANOVA, P<0.05) greater than 51.68±9.78%, by Cis-GNs. This was also illustrated by CLSM images, which indicated that Cis-GNs-FA preferably accumulated in the cytoplasm of HeLa cells nearby nucleus by following receptor-mediated endocytosis pathway as compared to Cis-GNs. ConclusionTherefore, Cis-GNs-FA warrants further in-depth in vitro and in vivo investigations to scale up the technology for clinical translation.

Study of the deformation-driving [formula omitted] orbital in 6728Ni39 using one-neutron transfer reactions

The νg9/2,d5/2,s1/2 orbitals are assumed to be responsible for the swift onset of collectivity observed in the region below 68Ni. Especially the single-particle energies and strengths of these orbitals are of importance. We studied such properties in the nearby 67Ni nucleus, by performing a (d,p)-experiment in inverse kinematics employing a post-accelerated radioactive ion beam (RIB) at the REX-ISOLDE facility. The experiment was performed at an energy of 2.95 MeV/u using a combination of the T-REX particle detectors, the Miniball γ-detection array and a newly-developed delayed-correlation technique as to investigate μs-isomers. Angular distributions of the ground state and multiple excited states in 67Ni were obtained and compared with DWBA cross-section calculations, leading to the identification of positive-parity states with substantial νg9/2 (1007 keV) and νd5/2 (2207 keV and 3277 keV) single-particle strengths up to an excitation energy of 5.8 MeV. 50% of the νd5/2 single-particle strength relative to the νg9/2-orbital is concentrated in and shared between the first two observed 5/2+ levels. A comparison with extended Shell Model calculations and equivalent (3He, d) studies in the region around 9040Zr50 highlights similarities for the strength of the negative-parity pf and positive-parity g9/2 state, but differences are observed for the d5/2 single-particle strength.

Eyelid apraxia associated with deep brain stimulation of the periaqueductal gray area

We report a patient with eyelid apraxia following deep brain stimulation of the periaqueductal gray area. Based on the position of our electrode, we argue that the phenomenon is linked to inhibition of the nearby central caudal nucleus of the oculomotor nucleus by high frequency stimulation.

Nuclear Reaction Induced by Carrier-Envelope-Phase Controlled Proton Recollision in a Laser-Driven Molecule

Nuclear reactions induced by proton recollision with a nearby nucleus are studied in a setup where a neutral molecule is exposed to an extremely intense, few-cycle laser pulse. At the rising edge of the laser pulse, all electrons in the molecule are first ejected by field ionization, resulting in a molecule consisting of the bare nuclei only. A proton in the bare molecule is subsequently accelerated by the laser field in such a way that it recollides with a nearby, heavier nucleus, with a kinetic energy high enough to induce a nuclear reaction. As a specific example, the probability of triggering the (15)N(p,α)(12)C reaction by exposing either a (15)NH molecule or a (15)NH3 molecule to an intense laser pulse is calculated using the classical trajectory Monte Carlo method. We show that the proton recollision process can be controlled both by varying the carrier-envelope phase of the laser field and by the degree of molecular orientation. We also find that the magnetic field of the laser pulse plays a crucial role in the recollision dynamics.

PGO activity after carbachol delivery in the oral and caudal pontine reticular nuclei: similarities and differences with spontaneous REM sleep in cats

Carbachol in the ventral part of the oral pontine reticular nucleus (vRPO) generates REM sleep with all its polygraphic characteristics. In contrast, cholinergic stimulation of the nearby rostral caudal pontine reticular nucleus (RPC) produces atonia and PGOs but with EEG sychronization. By quantifying PGO activity, this study further characterizes the effects of carbachol in these two pontine sites. Eight cats wearing electrodes for sleep polygraphic recordings were used; each had a guide-tube aimed at the vRPO or the RPC to administer carbachol (0.1 M, 20–30 nl) microinjections. Isolated PGO waves (Type I) and clusters with interspike intervals of ⩽330 ms of 2, 3 and ⩾4 PGOs (Type II, III and IV respectively) were quantified using one-minute epochs of 4 consecutive spontaneous REM sleep episodes (control) and then after carbachol in the vRPO and the RPC at the following times: when PGO activity was first detected (T0) and 10–15 (T10), 30–45 (T30) and 60–75 (T60) min later. Data from the different experimental conditions were compared with ANOVAs for repeated measures and the post hoc Fisher test. Atonia, desynchronized EEG and different types of PGOs occurred shortly after carbachol delivery in the vRPO, while a predominance of Type IV PGO clusters, numerous REMs, atonia and with a striking EEG theta synchronization occurred after carbachol in the RPC. The total number of PGOs and Type IV clusters were significantly higher in RPC experiments than in either spontaneous or vRPO Rem sleep in the T0 to T60 samples. These parameters were slightly lower than the spontaneous REM sleep values after vRPO carbachol delivery but, significant decreases only occurred immediately after the first appearance of PGO activity (T0). Also, the four PGO type proportions were fairly well preserved in carbachol vRPO experiments. In the RPC experiments, the proportions of the PGO patterns were different from spontaneous or carbachol vRPO Rem sleep (Types I and II significantly decreased and Type IV significantly increased). These results indicate that the vRPO is not only the prime region for the simultaneous appearance of tonic REM sleep signs (atonia and EEG desynchonization) but it can also to promote the cascade of events that establish the physiological pattern of PGO phasic activities. Cholinergic stimulation of the rostral RPC does not generate true REM sleep, but it is involved in the generation of atonia and of long trains of clustered PGO activity. Supported by Grant BFU2009-06991 from MCyT, Spain.

Genesis of the Au–Bi–Cu–As, Cu–Mo ± W, and base–metal Au–Ag mineralization at the Mountain Freegold (Yukon, Canada): constraints from Ar–Ar and Re–Os geochronology and Pb and stable isotope compositions

The genesis of mineralized systems across the Mountain Freegold area, in the Dawson Range Cu–Au ± Mo Belt of the Tintina Au province was constrained using Pb and stable isotope compositions and Ar–Ar and Re–Os geochronology. Pb isotope compositions of sulfides span a wide compositional range (206Pb/204Pb, 18.669–19.861; 208Pb/204Pb, 38.400–39.238) that overlaps the compositions of the spatially associated igneous rocks, thus indicating a magmatic origin for Pb and probably the other metals. Sulfur isotopic compositions of sulfide minerals are broadly similar and their δ34S (Vienna-Canyon Diablo Troilite (V-CDT)) values range from −1.4 to 3.6 ‰ consistent with the magmatic range, with the exception of stibnite from a Au–Sb–quartz vein, which has δ34S values between −8.1 and −3.1 ‰. The δ34S values of sulfates coexisting with sulfide are between 11.2 and 14.2 ‰; whereas, those from the weathering zone range from 3.7 to 4.3 ‰, indicating supergene sulfates derived from oxidation of hypogene sulfides. The δ13C (Vienna Peedee Belemnite (VPDB)) values of carbonate range from −4.9 to 1.1 ‰ and are higher than magmatic values. The δ18O (V-SMOW) values of magmatic quartz phenocrysts and magmatic least-altered rocks vary between 6.2 and 10.1 ‰ and between 5.0 and 10.1 ‰, respectively, whereas altered magmatic rocks and hydrothermal minerals (quartz and magnetite) are relatively 18O-depleted (4.2 to 7.9 ‰ and −6.3 to 1.5 ‰, respectively). Hydrogen isotope compositions of both least-altered and altered igneous rock samples are D-depleted (from −133 to −161 ‰ Vienna-Standard Mean Ocean Water (V-SMOW)), consistent with differential magma degassing and/or post-crystallization exchange between the rocks and meteoric ground water. Zircon from a chlorite-altered dike has a U–Pb crystallization age of 108.7 ± 0.4 Ma; whereas, the same sample yielded a whole-rock Ar–Ar plateau age of 76.25 ± 0.53 Ma. Likewise, molybdenite Re–Os model ages range from 75.8 to 78.2 Ma, indicating the mineralizing events are genetically related to Late Cretaceous volcano-plutonic intrusions in the area. The molybdenite Re–Os ages difference between the nearby Nucleus (75.9 ± 0.3 to 76.2 ± 0.3 Ma) and Revenue (77.9 ± 0.3 to 78.2 ± 0.3 Ma) mineral occurrences suggests an episodic mineralized system with two pulses of hydrothermal fluids separated by at least 2 Ma. This, in combination with geological features suggest the Nucleus deposit represents the apical and younger portion of the Revenue–Nucleus magmatic-hydrothermal system and may suggest an evolution from the porphyry to the epithermal environments.

NUCLEAR RADIO JET FROM A LOW-LUMINOSITY ACTIVE GALACTIC NUCLEUS IN NGC 4258

The nearby low-luminosity active galactic nucleus (LLAGN) NGC 4258 has a weak radio continuum component at the galactic center. We investigate its radio spectral properties on the basis of our new observations using the Nobeyama Millimeter Array at 100 GHz and archival data from the Very Large Array (VLA) at 1.7-43 GHz and the James Clerk Maxwell telescope at 347 GHz. The NGC 4258 nuclear component exhibits (1) an intra-month variable and complicated spectral feature at 5-22 GHz and (2) a slightly inverted spectrum at 5-100 GHz (a spectral index of ~0.3) in time-averaged flux densities, which are also apparent in the closest LLAGN M81. These similarities between NGC 4258 and M81 in radio spectral natures in addition to previously known core shift in their AU-scale jet structures produce evidence that the same mechanism drives their nuclei. We interpret the observed spectral property as the superposition of emission spectra originating at different locations with frequency-dependent opacity along the nuclear jet. Quantitative differences between NGC 4258 and M81 in terms of jet/counter jet ratio, radio loudness, and degree of core shift can be consistently understood by fairly relativistic speeds (bulk Lorentz factors of >~ 3) of jet and their quite different inclinations. The picture established from the two closest LLAGNs is useful for understanding the physical origin of unresolved and flat/inverted spectrum radio cores that are prevalently found in LLAGNs, including Sgr A*, with starved supermassive black holes in the present-day universe.

Dynamics of neuromodulatory feedback determines frequency modulation in a reduced respiratory network: A computational study

Neuromodulators, such as amines and neuropeptides, alter the activity of neurons and neuronal networks. In this work, we investigate how neuromodulators, which activate Gq-protein second messenger systems, can modulate the bursting frequency of neurons in a critical portion of the respiratory neural network, the pre-Bötzinger complex (preBötC). These neurons are a vital part of the ponto-medullary neuronal network, which generates a stable respiratory rhythm whose frequency is regulated by neuromodulator release from the nearby Raphe nucleus. Using a simulated 50-cell network of excitatory preBötC neurons with a heterogeneous distribution of persistent sodium conductance and Ca2+, we determined conditions for frequency modulation in such a network by simulating interaction between Raphe and preBötC nuclei. We found that the positive feedback between the Raphe excitability and preBötC activity induces frequency modulation in the preBötC neurons. In addition, the frequency of the respiratory rhythm can be regulated via phasic release of excitatory neuromodulators from the Raphe nucleus. We predict that the application of a Gq antagonist will eliminate this frequency modulation by the Raphe and keep the network frequency constant and low. In contrast, application of a Gq agonist will result in a high frequency for all levels of Raphe stimulation. Our modeling results also suggest that high [K+] requirement in respiratory brain slice experiments may serve as a compensatory mechanism for low neuromodulatory tone.

ESR study of some gamma irradiated amino acids and condensed 1,4-dihydropyridines

L-alanine methyl ester hydrochloride, 2-aminoisobutyric acid and some condensed 1,4-dihydropyridine derivatives (Compounds R1–R4) were gamma irradiated, the induced free radicals was investigated at room temperature by electron spin resonance techniques. The observed paramagnetic species of amino acids compounds were attributed to the CH3ĊHCOOCH3 and (CH3)2ĊCOOH radicals, respectively. The observed spectra of the 1,4-dihydropyridine derivatives interpreted in terms of some type of amine radical fragments. The spectra were computer simulated and the g values of the radicals and the hyperfine structure constants of the unpaired electron with nearby protons and 14N nucleus were determined. In this study, the observed paramagnetic species were found to be stable at room temperature more than 2months.

Dynamics of neuromodulatory feedback determines frequency modulation in respiratory network

Neuromodulators, such as amines and neuropeptides, alter the activity of neurons and neuronal networks. In this work, we investigate how neuromodulators which activate Gq-protein second messenger systems can modulate the frequency of bursting neurons in a critical portion of the respiratory neural network, the pre-Botzinger complex (pBC). These neurons are a vital part of the ponto-medullary neuronal network, which generates a stable respiratory rhythm, whose frequency is modulated by neuromodulator release from nearby Raphe nucleus. Using a simulated 50-cell network of excitatory connected pBC neurons with a heterogeneous distribution of persistent sodium conductance and ER Ca2+, we determined conditions for frequency modulation in such network by simulating interaction between Raphe and pBC nuclei. We found that the positive feedback between the Raphe excitability and pBC activity induces frequency modulation in the pBC neurons. In addition, the frequency of the respiratory rhythm can be modulated via phasic release of excitatory neuromodulators from the Raphe nucleus. We further predict that the application of a Gq antagonist will eliminate this frequency modulation by Raphe and keep the network frequency constant and low. In contrast, application of a Gq agonist will result in a high frequency for all levels of Raphe stimulation. Our modeling results also suggest that high [K+] requirement in respiratory brain slice experiments may serve as a compensatory mechanism for low neuromodulatory tone.

Heterogeneity in Mitochondrial Morphology and Membrane Potential Is Independent of the Nuclear Division Cycle in Multinucleate Fungal Cells

In the multinucleate filamentous fungus Ashbya gossypii, nuclei divide asynchronously in a common cytoplasm. We hypothesize that the division cycle machinery has a limited zone of influence in the cytoplasm to promote nuclear autonomy. Mitochondria in cultured mammalian cells undergo cell cycle-specific changes in morphology and membrane potential and therefore can serve as a reporter of the cell cycle state of the cytoplasm. To evaluate if the cell cycle state of nuclei in A. gossypii can influence the adjacent cytoplasm, we tested whether local mitochondrial morphology and membrane potential in A. gossypii are associated with the division state of a nearby nucleus. We found that mitochondria exhibit substantial heterogeneity in both morphology and membrane potential within a single multinucleated cell. Notably, differences in mitochondrial morphology or potential are not associated with a specific nuclear division state. Heterokaryon mutants with a mixture of nuclei with deletions of and wild type for the mitochondrial fusion/fission genes DNM1 and FZO1 exhibit altered mitochondrial morphology and severe growth and sporulation defects. This dominant effect suggests that the gene products may be required locally near their expression site rather than diffusing widely in the cell. Our results demonstrate that mitochondrial dynamics are essential in these large syncytial cells, yet morphology and membrane potential are independent of nuclear cycle state.

Cells in the female retrotrapezoid region upregulate c-fos in response to 10%, but not 5%, carbon dioxide

The retrotrapezoid nucleus (RTN) is thought to regulate breathing in response to changes in blood carbon dioxide (CO 2), and to make a vital contribution to respiratory drive, especially during sleep. However, cells in the female RTN fail to upregulate c-fos in response to low level CO 2 exposure, while cells in the male RTN have a robust upregulation of c-fos in response to low level CO 2 exposure. In this study, we examined the possibility that the female RTN has a higher threshold for c-fos upregulation in response to CO 2. Following exposure of Fos-Tau-LacZ (FTL) transgenic mice to 10% CO 2, c-fos was upregulated in just as many cells in the female as in the male RTN. In addition, the male RTN responded equivalently to 5% and 10% CO 2, consistent with a lack of a dose response to CO 2 in the male RTN. Cells in the nearby facial nucleus upregulated c-fos in the same number of cells regardless of sex or gas exposure, confirming that the sex difference in the RTN is unique to that nucleus. We propose that the male and female RTN upregulate c-fos differently in response to CO 2 due to differences in the transcriptional regulation by estrogens of genes that encode proteins related to neuronal excitability or specifically related to central chemoreception, such as potassium channels. These findings could have clinical relevance to sleep related breathing disorders that disproportionately affect males, including the sudden infant death syndrome and sleep apnea.