416 research outputs found
Gold nanosponges (AuNS): a versatile nanostructure for surface-enhanced Raman spectroscopic detection of small molecules and biomolecules
No full textPrepared by simple pour and mix chemistry, gold nanosponges (AuNS) are versatile structures for surface-enhanced Raman spectroscopy (SERS). An investigation into the enhancement is performed by relating the nanostructure's morphology to the SERS signal. The potential of the AuNS in SERS-based molecular and biomolecular detection is introduced
Gq Protein-Coupled Membrane-Initiated Estrogen Signaling Rapidly Excites Corticotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus in Female Mice
No full textCRH neurons in the hypothalamic paraventricular nucleus (PVN) play a central role in regulating the hypothalamus-pituitary-adrenal (HPA) axis and are directly influenced by 17β-estradiol (E2). Although compelling evidence has suggested the existence of membrane-associated estrogen receptors (mERs) in hypothalamic and other central nervous system neurons, it remains unknown whether E2 impacts CRH neuronal excitability through this mechanism. The purpose of the current study is to examine the existence and function of mER signaling in PVN CRH neurons. Whole-cell recordings were made from CRH neurons identified by Alexa Fluor 594 labeling and post hoc immunostaining in ovariectomized female mice. E2 (100nM) rapidly suppressed the M-current (a voltage-dependent K(+) current) and potentiated glutamatergic excitatory postsynaptic currents. The putative Gq-coupled mER (Gq-mER) characterized in hypothalamic proopiomelanocortin neurons initiates a phospholipase C-protein kinase C-protein kinase A pathway; therefore, we examined the involvement of this pathway using selective inhibitors. Indeed, the ER antagonist ICI 182780 and inhibitors of Gq-phospholipase C-protein kinase C-protein kinase A blocked E2's actions, suggesting dependence on the Gq-mER. Furthermore, STX, a selective ligand for the Gq-mER, mimicked E2's actions. Finally, to examine the in vivo effect of Gq-mER activation, E2 or STX injection increased c-fos expression in CRH neurons in the PVN, suggesting CRH neuronal activation. This corresponded to an increase in plasma corticosterone. We conclude that the Gq-mER plays a critical role in the rapid regulation of CRH neuronal activity and the HPA axis. Our findings provide a potential underlying mechanism for E2's involvement in the pathophysiology of HPA-associated mood disorders.Peer reviewe
Endothelin Type B Receptor–Induced Sustained Ca2+ Influx Involves Gq/11/Phospholipase C–Independent, p38 Mitogen-Activated Protein Kinase–Dependent Activation of Na+/H+ Exchanger
No full textThe mechanism for sustained Ca2+ influx activated by G protein-coupled receptors was examined. In Chinese hamster ovary cells expressing recombinant human endothelin type B receptor (ETBR) and endogenous P2Y receptor (P2Y-R), endothelin-1 elicited a sustained Ca2+ influx depending on Gq/11 protein, phospholipase C (PLC), Na+/H+ exchanger (NHE) and p38 mitogen-activated protein kinase (p38MAPK), whereas P2Y-R-induced sustained Ca2+ influx was negligible. Functional study showed that NHE activation by ETBR was mediated via p38MAPK but not Gq/11/PLC, while that by P2Y-R involves only Gq/11/PLC/p38MAPK. These results suggest that Gq/11/PLC-independent NHE activation via p38MAPK plays an important role in ETBR-mediated sustained Ca2+ influx
GQ corrections in the circuit theory of quantum transport
No full textWe develop a finite-element technique that allows one to evaluate correction of the order of GQ to various transport characteristics of arbitrary nanostructures. Common examples of such corrections are the weak-localization effect on conductance and universal conductance fluctuations. Our approach, however, is not restricted to conductance only. It allows one in the same manner to evaluate corrections to the noise characteristics, superconducting properties, strongly nonequilibrium transport, and transmission distribution. To enable such functionality, we consider Green’s functions of arbitrary matrix structure. We derive a finite-element technique from Cooperon and diffuson ladders for these Green’s functions. The derivation is supplemented with application examples. Those include transitions between ensembles and the Aharonov-Bohm effect.Kavli Institute of NanoscienceApplied Science
ALMA MEASUREMENTS OF CIRCUMSTELLAR MATERIAL IN THE GQ LUP SYSTEM
No full textWe present Atacama Large Millimeter/submillimeter Array observations of the GQ Lup system, a young Sun-like star with a substellar-mass companion in a wide-separation orbit. These observations of 870 mu m continuum and CO J = 3-2 line emission with beam size similar to 0."3 (similar to 45 au) resolve the disk of dust and gas surrounding the primary star, GQ Lup A, and provide deep limits on any circumplanetary disk surrounding the companion, GQ Lup b. The circumprimary dust disk is compact with an FWHM of 59 +/- 12 au, while the gas has a larger extent with a characteristic radius of 46.5 +/- 1.8 au. By forward-modeling the velocity field of the circumprimary disk based on the CO emission, we constrain the mass of GQ Lup. A to be M-* = (1.03 +/- 0.05) * (d/156 pc) M-circle dot, where d is a known distance, and determine that we view the disk at an inclination angle of 60 degrees 5 +/- 0 degrees 5 and a position angle of 346 degrees +/- 1 degrees. The 3s upper limit on the 870 mu m flux density of any circumplanetary disk associated with GQ Lup b of <0.15 mJy implies an upper limit on the dust disk mass of <0.04M(circle dot) for standard assumptions about optically thin emission. We discuss proposed mechanisms for the formation of wide-separation substellar companions given the non-detection of circumplanetary disks around GQ Lup b and other similar systems.National Science Foundation Graduate Research Fellowship [DGE1144152]; NRAO Student Observing SupportSCI(E)ARTICLE183
Han clans and villages - An anthropological dialogue and reflection
No full textAnthropologySociologySSCI0ARTICLE483-983
Two-step structural changes in M3 muscarinic receptor activation rely on the coupled Gq protein cycle
No full textG protein-coupled receptors (GPCRs) regulate diverse intracellular signaling pathways through the activation of heterotrimeric G proteins. However, the effects of the sequential activation–deactivation cycle of G protein on the conformational changes of GPCRs remains unknown. By developing a Förster resonance energy transfer (FRET) tool for human M3 muscarinic receptor (hM3R), we find that a single-receptor FRET probe can display the consecutive structural conversion of a receptor by G protein cycle. Our results reveal that the G protein activation evokes a two-step change in the hM3R structure, including the fast step mediated by Gq protein binding and the subsequent slower step mediated by the physical separation of the Gαq and Gβγ subunits. We also find that the separated Gαq-GTP forms a stable complex with the ligand-activated hM3R and phospholipase Cβ. In sum, the present study uncovers the real-time conformational dynamics of innate hM3R during the downstream Gq protein cycle. © 2023, The Author(s).TRUEsciescopu
RV Measurements of Directly Imaged Brown Dwarf GQ Lup B to Search for Exosatellites
No full textGQ Lup B is one of the few substellar companions with a detected cicumplanetary disk (CPD). Observations of the CPD suggest the presence of a cavity, possibly formed by an exosatellite. Using the Keck Planet Imager and Characterizer (KPIC), a high-contrast imaging suite that feeds a high-resolution spectrograph (1.9–2.5 µ m, R ∼35,000), we present the first dedicated radial velocity (RV) observations around a high-contrast, directly imaged substellar companion, GQ Lup B, to search for exosatellites. Over 11 epochs, we find a best and median RV error of 400–1000 m s ^−1 , most likely limited by systematic fringing in the spectra due to transmissive optics within KPIC. With this RV precision, KPIC is sensitive to exomoons 0.6%–2.8% the mass of GQ Lup B (∼30 M _Jup ) at separations between the Roche limit and 65 R _Jup , or the extent of the cavity inferred within the CPD detected around GQ Lup B. Using simulations of HISPEC, a high resolution infrared spectrograph planned to debut at W.M. Keck Observatory in 2026, we estimate future exomoon sensitivity to increase by over an order of magnitude, providing sensitivity to less massive satellites potentially formed within the CPD itself. Additionally, we run simulations to estimate the amount of material that different masses of satellites could clear in a CPD to create the observed cavity. We find satellite-to-planet mass ratios of q > 2 × 10 ^−4 can create observable cavities and report a maximum cavity size of ∼51 R _Jup carved from a satellite
Targeting G-quadruplex Forming Sequences with Cas9
No full textClustered regularly interspaced palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins, particularly Cas9, have provided unprecedented control on targeting and editing specific DNA sequences. If the target sequences are prone to folding into noncanonical secondary structures, such as G-quadruplex (GQ), the conformational states and activity of the CRISPR-Cas9 complex may be influenced, but the impact has not been assessed. Using single molecule FRET, we investigated structural characteristics of the complex formed by CRISPR-Cas9 and target DNA, which contains a potentially GQ forming sequence (PQS) in either the target or the nontarget strand (TS or NTS). We observed different conformational states and dynamics depending on the stability of the GQ and the position of PQS. When PQS was in NTS, we observed evidence for GQ formation for both weak and stable GQs. This is consistent with R-loop formation between TS and crRNA releasing NTS from Watson-Crick pairing and facilitating secondary structure formation in it. When PQS was in TS, R-loop formation was adequate to maintain a weak GQ in the unfolded state but not a GQ with moderate or high stability. The observed structural heterogeneity within the target dsDNA and the R-loop strongly depended on whether the PQS was in TS or NTS. We propose these variations in the complex structures to have functional implications for Cas9 activity. BN/Chirlmin Joo La
RV measurements of directly imaged brown dwarf GQ Lup B to search for exo-satellites
No full textGQ Lup B is one of the few substellar companions with a detected cicumplanetary disk, or CPD. Observations of the CPD suggest the presence of a cavity, possibly formed by an exo-satellite. Using the Keck Planet Imager and Characterizer (KPIC), a high contrast imaging suite that feeds a high resolution spectrograph (1.9-2.5 microns, R35,000), we present the first dedicated radial velocity (RV) observations around a high-contrast, directly imaged substellar companion, GQ Lup B, to search for exo-satellites. Over 11 epochs, we find a best and median RV error of 400-1000 m/s, most likely limited by systematic fringing in the spectra due to transmissive optics within KPIC. With this RV precision, KPIC is sensitive to exomoons 0.6-2.8% the mass of GQ Lup B () at separations between the Roche limit and , or the extent of the cavity inferred within the CPD detected around GQ Lup B. Using simulations of HISPEC, a high resolution infrared spectrograph planned to debut at W.M. Keck Observatory in 2026, we estimate future exomoon sensitivity to increase by over an order of magnitude, providing sensitivity to less massive satellites potentially formed within the CPD itself. Additionally, we run simulations to estimate the amount of material that different masses of satellites could clear in a CPD to create the observed cavity. We find satellite-to-planet mass ratios of can create observable cavities and report a maximum cavity size of carved from a satellite.15 pages, 5 figure
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