Daily Eastern News: November 10, 1975

https://thekeep.eiu.edu/den_1975_nov/1005/thumbnail.jp

TMEM16A and TMEM16B modulate pheromone-evoked action potential firing in mouse vomeronasal sensory neurons

The mouse vomeronasal system controls several social behaviors. Pheromones and other social cues are detected by sensory neurons in the vomeronasal organ (VNO). Stimuli activate a transduction cascade that leads to membrane potential depolarization, increase in cytosolic Ca2+ level, and increased firing. The Ca2+-activated chloride channels TMEM16A and TMEM16B are co-expressed within microvilli of vomeronasal neurons, but their physiological role remains elusive. Here, we investigate the contribution of each of these channels to vomeronasal neuron firing activity by comparing wild-type (WT) and knock-out (KO) mice. Performing loosepatch recordings from neurons in acute VNO slices, we show that spontaneous activity is modified by Tmem16a KO, indicating that TMEM16A, but not TMEM16B, is active under basal conditions. Upon exposure to diluted urine, a rich source of mouse pheromones, we observe significant changes in activity. Vomeronasal sensory neurons (VSNs) from Tmem16a cKO and Tmem16b KO mice show shorter interspike intervals (ISIs) compared with WT mice, indicating that both TMEM16A and TMEM16B modulate the firing pattern of pheromone-evoked activity in VSNs

Diffuse reflection of ultracold neutrons from low-roughness surfaces

We report a measurement of the reflection of ultracold neutrons from flat, large-area plates of different Fermi potential materials with low surface roughness. The results were used to test two diffuse reflection models, the well-known Lambert model and the micro-roughness model which is based on wave scattering. The Lambert model fails to reproduce the diffuse reflection data. The surface roughness b and correlation length w , obtained by fitting the micro-roughness model to the data are in the range 1$\le$ b $\le$3 nm and 10$\le$ w $\le$120 nm, in qualitative agreement with independent measurements using atomic force microscop

An Improved Neutron Electric Dipole Moment Experiment

A new measurement of the neutron EDM, using Ramsey's method of separated oscillatory fields, is in preparation at the new high intensity source of ultra-cold neutrons (UCN) at the Paul Scherrer Institute, Villigen, Switzerland (PSI). The existence of a non-zero nEDM would violate both parity and time reversal symmetry and, given the CPT theorem, might lead to a discovery of new CP violating mechanisms. Already the current upper limit for the nEDM (|d_n|<2.9E-26 e.cm) constrains some extensions of the Standard Model. The new experiment aims at a two orders of magnitude reduction of the experimental uncertainty, to be achieved mainly by (1) the higher UCN flux provided by the new PSI source, (2) better magnetic field control with improved magnetometry and (3) a double chamber configuration with opposite electric field directions. The first stage of the experiment will use an upgrade of the RAL/Sussex/ILL group's apparatus (which has produced the current best result) moved from Institut Laue-Langevin to PSI. The final accuracy will be achieved in a further step with a new spectrometer, presently in the design phase.Comment: Flavor Physics & CP Violation Conference, Taipei, 200

Synchronous Infra-Slow Oscillations Organize Ensembles of Accessory Olfactory Bulb Projection Neurons into Distinct Microcircuits

The accessory olfactory system controls social and sexual behavior. In the mouse accessory olfactory bulb, the first central stage of information processing along the accessory olfactory pathway, projection neurons (mitral cells) display infra-slow oscillatory discharge with remarkable periodicity. The physiological mechanisms that underlie this default output state, however, remain controversial. Moreover, whether such rhythmic infra-slow activity patterns exist in awake behaving mice and whether such activity reflects the functional organization of the accessory olfactory bulb circuitry remain unclear. Here, we hypothesize that mitral cell ensembles form synchronized microcircuits that subdivide the accessory olfactory bulb into segregated functional clusters. We use a miniature microscope to image the Ca2+ dynamics within the apical dendritic compartments of large mitral cell ensembles in vivo. We show that infra-slow periodic patterns of concerted neural activity, indeed, reflect the idle state of accessory olfactory bulb output in awake male and female mice. Ca2+ activity profiles are distinct and glomerulus-specific. Confocal time-lapse imaging in acute slices reveals that groups of mitral cells assemble into microcircuits that exhibit correlated Ca2+ signals. Moreover, electrophysiological profiling of synaptic connectivity indicates functional coupling between mitral cells. Our results suggest that both intrinsically rhythmogenic neurons and neurons entrained by fast synaptic drive are key elements in organizing the accessory olfactory bulb into functional microcircuits, each characterized by a distinct default pattern of infra-slow rhythmicity

Membrane permeation of arginine-rich cell-penetrating peptides independent of transmembrane potential as a function of lipid composition and membrane fluidity

Cell-penetrating peptides (CPPs) are prominent delivery vehicles to confer cellular entry of (bio-) macromolecules. Internalization efficiency and uptake mechanism depend, next to the type of CPP and cargo, also on cell type. Direct penetration of the plasma membrane is the preferred route of entry as this circumvents endolysosomal sequestration. However, the molecular parameters underlying this import mechanism are still poorly defined. Here, we make use of the frequently used HeLa and HEK cell lines to address the role of lipid composition and membrane potential. In HeLa cells, at low concentrations, the CPP nona-arginine (R9) enters cells by endocytosis. Direct membrane penetration occurs only at high peptide concentrations through a mechanism involving activation of sphingomyelinase which converts sphingomyelin into ceramide. In HEK cells, by comparison, R9 enters the cytoplasm through direct membrane permeation already at low concentrations. This direct permeation is strongly reduced at room temperature and upon cholesterol depletion, indicating a complex dependence on membrane fluidity and microdomain organisation. Lipidomic analyses show that in comparison to HeLa cells HEK cells have an endogenously low sphingomyelin content. Interestingly, direct permeation in HEK cells and also in HeLa cells treated with exogenous sphingomyelinase is independent of membrane potential. Membrane potential is only required for induction of sphingomyelinase-dependent uptake which is then associated with a strong hyperpolarization of membrane potential as shown by whole-cell patch clamp recordings. Next to providing new insights into the interplay of membrane composition and direct permeation, these results also refute the long-standing paradigm that transmembrane potential is a driving force for CPP uptake

Sensory Measurements: Coordination and Standardization

Do sensory measurements deserve the label of “measurement”? We argue that they do. They fit with an epistemological view of measurement held in current philosophy of science, and they face the same kinds of epistemological challenges as physical measurements do: the problem of coordination and the problem of standardization. These problems are addressed through the process of “epistemic iteration,” for all measurements. We also argue for distinguishing the problem of standardization from the problem of coordination. To exemplify our claims, we draw on olfactory performance tests, especially studies linking olfactory decline to neurodegenerative disorders

Gravitational depolarization of ultracold neutrons: comparison with data

We compare the expected effects of so-called gravitationally enhanced depolarization of ultracold neutrons to measurements carried out in a spin-precession chamber exposed to a variety of vertical magnetic-field gradients. In particular, we have investigated the dependence upon these field gradients of spin-depolarization rates and also of shifts in the measured neutron Larmor precession frequency. We find excellent qualitative agreement, with gravitationally enhanced depolarization accounting for several previously unexplained features in the data

Measurement of the permanent electric dipole moment of the neutron

We present the result of an experiment to measure the electric dipole moment EDM) of the neutron at the Paul Scherrer Institute using Ramsey's method of separated oscillating magnetic fields with ultracold neutrons (UCN). Our measurement stands in the long history of EDM experiments probing physics violating time reversal invariance. The salient features of this experiment were the use of a Hg-199 co-magnetometer and an array of optically pumped cesium vapor magnetometers to cancel and correct for magnetic field changes. The statistical analysis was performed on blinded datasets by two separate groups while the estimation of systematic effects profited from an unprecedented knowledge of the magnetic field. The measured value of the neutron EDM is d_{\rm n} = (0.0\pm1.1_{\rm stat}\pm0.2_{\rmsys})\times10^{-26}e\,{\rm cm}

Eliminating the mystery from the concept of emergence

While some branches of complexity theory are advancing rapidly, the same cannot be said for our understanding of emergence. Despite a complete knowledge of the rules underlying the interactions between the parts of many systems, we are often baffled by their sudden transitions from simple to complex. Here I propose a solution to this conceptual problem. Given that emergence is often the result of many interactions occurring simultaneously in time and space, an ability to intuitively grasp it would require the ability to consciously think in parallel. A simple exercise is used to demonstrate that we do not possess this ability. Our surprise at the behaviour of cellular automata models, and the natural cases of pattern formation they mimic, is then explained from this perspective. This work suggests that the cognitive limitations of the mind can be as significant a barrier to scientific progress as the limitations of our senses