Patch-Clamp Analysis of Voltage-Activated and Chemically Activated Currents in the Vomeronasal Organ Of Sternotherus Odoratus (Stinkpot/Musk Turtle)

The electrophysiological basis of chemical communication in the specialized olfactory division of the vomeronasal (VN) organ is poorly understood. In total, 198 patch-clamp recordings were made from 42 animals (Sternotherus odoratus, the stinkpot/musk turtle) to study the electrically and chemically activated properties of VN neurons. The introduction of tetramethylrhodamine-conjugated dextran into the VN orifice permitted good visualization of the vomeronasal neural epithelium prior to dissociating it into single neurons. Basic electrical properties of the neurons were measured (resting potential, -54.5 +/- 2.7 mV, N=11; input resistance, 6.7 +/- 1.4 G Omega, N=25; capacitance, 4.2 +/- 0.3 pF, N=22; means +/- S.E.M.). The voltage-gated K(+) current inactivation rate was significantly slower in VN neurons from males than in those from females, and K(+) currents in males were less sensitive (greater K(i)) to tetraethylammonium. Vomeronasal neurons were held at a holding potential of -60 mV and tested for their response to five natural chemicals, female urine, male urine, female musk, male musk and catfish extract. Of the 90 VN neurons tested, 33 (34 %) responded to at least one of the five compounds. The peak amplitude of chemically evoked currents ranged from 4 to 180 pA, with two-thirds of responses less than 25 pA. Urine-evoked currents were of either polarity, whereas musk and catfish extract always elicited only inward currents. Urine applied to neurons harvested from female animals evoked currents that were 2-3 times larger than those elicited from male neurons. Musk-evoked inward currents were three times the magnitude of urine- or catfish-extract-evoked inward currents. The calculated breadth of responsiveness for neurons presented with this array of five chemicals indicated that the mean response spectrum of the VN neurons is narrow (H metric 0.11). This patch-clamp study indicates that VN neurons exhibit sexual dimorphism in function and specificity in response to complex natural chemicals.io

Illuminating Vertebrate Olfactory Processing

The olfactory system encodes information about molecules by spatiotemporal patterns of activity across distributed populations of neurons and extracts information from these patterns to control specific behaviors. Recent studies used in vivo recordings, optogenetics, and other methods to analyze the mechanisms by which odor information is encoded and processed in the olfactory system, the functional connectivity within and between olfactory brain areas, and the impact of spatiotemporal patterning of neuronal activity on higher-order neurons and behavioral outputs. The results give rise to a faceted picture of olfactory processing and provide insights into fundamental mechanisms underlying neuronal computations. This review focuses on some of this work presented in a Mini-Symposium at the Annual Meeting of the Society for Neuroscience in 2012

Mapping odorant sensitivities reveals a sparse but structured representation of olfactory chemical space by sensory input to the mouse olfactory bulb

© 2022, Burton et al. This article is distributed under the terms of the Creative Commons Attribution License. https://creativecommons.org/licenses/by/4.0/In olfactory systems, convergence of sensory neurons onto glomeruli generates a map of odorant receptor identity. How glomerular maps relate to sensory space remains unclear. We sought to better characterize this relationship in the mouse olfactory system by defining glomeruli in terms of the odorants to which they are most sensitive. Using high-throughput odorant delivery and ultrasensitive imaging of sensory inputs, we imaged responses to 185 odorants presented at concentrations determined to activate only one or a few glomeruli across the dorsal olfactory bulb. The resulting datasets defined the tuning properties of glomeruli - and, by inference, their cognate odorant receptors - in a low-concentration regime, and yielded consensus maps of glomerular sensitivity across a wide range of chemical space. Glomeruli were extremely narrowly tuned, with ~25% responding to only one odorant, and extremely sensitive, responding to their effective odorants at sub-picomolar to nanomolar concentrations. Such narrow tuning in this concentration regime allowed for reliable functional identification of many glomeruli based on a single diagnostic odorant. At the same time, the response spectra of glomeruli responding to multiple odorants was best predicted by straightforward odorant structural features, and glomeruli sensitive to distinct odorants with common structural features were spatially clustered. These results define an underlying structure to the primary representation of sensory space by the mouse olfactory system.Peer reviewe

Early post-BMT liver function in children conditioned for bone marrow transplantation with busulfan-containing and with hyperfractionated TBI-containing preparative regimens

Liver toxicity following preparatory regimen (prep-reg) for bone marrow transplantation (BMT) creates one of the major problems in the early post-BMT period, especially in patients (pts.) with pretransplant HCV and/or HBV infections, and liver dysfunction. This gave rise to the search for prep-reg, that would be less hepatotoxic, but would still have sufficient antileukemic effect. Therefore, we compared liver function in children prepared for allo-BMT with busulfan-containing and with hyperfractionated TBI-containing regimens.Patients and methodsSeventeen pts. have been conditioned with busulfan-containing prep-reg (10 with BuVpCy, 7 with BuCy) (Bu-group). Diagnosis consisted of ALL (6) and AML (11). All pts. fram Bu-group have been transplanted with bone marrow from HLA-identical, MLC non-reactive siblings. Pretransplant screening showed positive HBsAg in one patient, and HCV antibody in 6 pts. For GvHD prevention CsA+MTX have been given in 12 pts., CsA+MTX+PRED in 3 pts., and CsA alone in 2 pts. Acute GvHD II- IVO occured in 4 pts. Hyperfractionated TBI (hFTBI) (2 × 1,5 Gy on 4 consecutive days) was employed in 10 pts. (hFTBI+Cy in 6 pts., hFTBI+Vp in 4 pts.) (hFTBI-group). Nine pts. were transplanted for ALL, and one child for AML. Nine pts. from hFTBI-graup have been transplanted with bone marraw fram HLA-identical, MLC non-reactive siblings, and one child from a syngeneic twin. For GvHD prevention 5 pts. have been treated with CsA+MTX, 2 with CsA+PRED, and 2 with CsA alone (recipient of syngeneic bone marrow received no GvHD prophylaxis). Acute GvHD IIO was observed in one child. For HVOD prevention in all children from both groups continuous infusion of alprostadil and/or low-dose heparin (100 units/kg/day) has been administered. Total bilirubine concentration, alanine aminotransferase (AIAt) and aspartate aminotransferase (AspAt) activity were measured in serum on day −10, −1, +7, +14, +21, +28 and +35 by automated chemical analysis using standard reagents.ResultsOne child (AML, pos. HCV antibody, BuCy, CsA alone for GvHD prevention) from Bu-group developed on day +18 day recurrent form of severe HVOD leading to the death on day +102.ConclusionsAccording to liver function parameters observed till day +35 post-BMT, ie. during the period, when the risk of HVOD is highest, hFTBI seems to be less hepatotoxic than busulfan-containing prep-reg. Therefore BM-recipients with liver dysfunction observed prior to BMT should rather be prepared for transplantation with hFTBI

Novel Orientational Ordering and Reentrant Metallicity in KxC60 Monolayers for 3 <= x <= 5

We have performed local STM studies on potassium-doped C60 (KxC60) monolayers over a wide regime of the phase diagram. As K content increases from x = 3 to 5, KxC60 monolayers undergo metal-insulator-metal reentrant phase transitions and exhibit a variety of novel orientational orderings. The most striking new structure has a pinwheel-like 7-molecule unit cell in insulating K4+dC60. We propose that the driving mechanism for the orientational ordering in KxC60 is the lowering of electron kinetic energy through maximization of the overlap of neighboring molecular orbitals over the entire doping range x = 3 to 5. In the insulating and metallic phases this gives rise to orbital versions of the superexchange and double-exchange interactions respectively.Comment: 16 pages, 4 figure

47. Allogeneic bone marrow transplantation in children with acute lymphoblastic leukemia in first and second complete remission conditioned with fractionated total body irradiation and etoposide or cyclophosphamide

Patients and methodsFrom 1993 to 2001 thirty two children underwent bone marrow transplantation (BMT) for ALL (12 in I CR and 20 in II CR after early BM or BM/organ relapse). Except 2 syngeneic all other were HLA-identical siblings transplants. All patients (pts) were conditioned with FTBI 2×1,5 Gy for 4 days (total dose 12 Gy) with lung shielding (9 Gy) and CY 60 mg/kg i.v for 2 days (total dose 120 mg/kg) (n=1 in I CR and n = 11 in II CR) or VP 60 mg/kg i.v (n = 11 in I CR and n = 9 in II CR), Pts in I CR have been given 1,1–4,9×108 MNC/kg (med. 2,7×108/kg), while pts in II CR 1,9–4,0×108 MNC/kg (med. 2,7×108/kg). For GvHD prevention CsA 3 mg/kg/d i.v was administered alone in 22 pts (n = 9 in I CR and n = 13 in II CR) or in combination with “short” MTX +/− PRED in 8 pts (n = 3 in I CR and n = 5 in II CR). Two pts transplanted with syngeneic BM received no GvHD prevention. Regimen related toxicity (RRT) was graded according to the system developed by Bearman et al. (1988).ResultsOnly mild or moderate expression of RRT was observed (GI toxicity, I°− 80%, II° −4%; stomatitis I° −40%, II° −20%; hepatic toxicity I°− 28%; renal, bladder and cardiac toxicity I°− 4%) and no transplant related deaths occured (TRM=0%). Among 12 pts transplanted in I CR only one child relapsed 4 months from BMT, while remaining 11 pts are alive in CCR with a median follow-up of 33months (range 6 to 66 months) and 92% probability of 5-year EFS. Of 20 children transplanted in II CR 6 relapsed 1–14 months from BMT (median 6,5 months). Fourteen of them remain in CCR with a median follow-up 19,5 months (range 1 to 96 months) and 66% probability of 8-year EFS.Conclusions1.In children with ALL the FTBI-12 Gy-containing regimen is well tolerated without the life-threatening toxic complications.2.FTBI-12 Gy-containing regimen demonstrates very good antileukemic efficacy for HR-ALL in I CR, but only limited for ALL in II CA.3.3. In context of good tolerance of FTBI in a total dose of 12 Gy and its limited antileukemic efficacy in children with ALL in II CR the escalation of FTBI total dose from 12 Gy to 13,2 Gy appears to be justified in those children. Supported by grant KBN 4 PO5E 108 18

Magnetic Vortex Core Reversal by Excitation of Spin Waves

Micron-sized magnetic platelets in the flux closed vortex state are characterized by an in-plane curling magnetization and a nanometer-sized perpendicularly magnetized vortex core. Having the simplest non-trivial configuration, these objects are of general interest to micromagnetics and may offer new routes for spintronics applications. Essential progress in the understanding of nonlinear vortex dynamics was achieved when low-field core toggling by excitation of the gyrotropic eigenmode at sub-GHz frequencies was established. At frequencies more than an order of magnitude higher vortex state structures possess spin wave eigenmodes arising from the magneto-static interaction. Here we demonstrate experimentally that the unidirectional vortex core reversal process also occurs when such azimuthal modes are excited. These results are confirmed by micromagnetic simulations which clearly show the selection rules for this novel reversal mechanism. Our analysis reveals that for spin wave excitation the concept of a critical velocity as the switching condition has to be modified.Comment: Minor corrections and polishing of previous versio