Visualizing Poiseuille flow of hydrodynamic electrons

Hydrodynamics is a general description for the flow of a fluid, and is expected to hold even for fundamental particles such as electrons when inter-particle interactions dominate. While various aspects of electron hydrodynamics were revealed in recent experiments, the fundamental spatial structure of hydrodynamic electrons, the Poiseuille flow profile, has remained elusive. In this work, we provide the first real-space imaging of Poiseuille flow of an electronic fluid, as well as visualization of its evolution from ballistic flow. Utilizing a scanning nanotube single electron transistor, we image the Hall voltage of electronic flow through channels of high-mobility graphene. We find that the profile of the Hall field across the channel is a key physical quantity for distinguishing ballistic from hydrodynamic flow. We image the transition from flat, ballistic field profiles at low temperature into parabolic field profiles at elevated temperatures, which is the hallmark of Poiseuille flow. The curvature of the imaged profiles is qualitatively reproduced by Boltzmann calculations, which allow us to create a 'phase diagram' that characterizes the electron flow regimes. Our results provide long-sought, direct confirmation of Poiseuille flow in the solid state, and enable a new approach for exploring the rich physics of interacting electrons in real space

<i>Escherichia coli</i> β-clamp slows down DNA polymerase I dependent nick translation while accelerating ligation

<div><p>The nick translation property of DNA polymerase I (Pol I) ensures the maturation of Okazaki fragments by removing primer RNAs and facilitating ligation. However, prolonged nick translation traversing downstream DNA is an energy wasting futile process, as Pol I simultaneously polymerizes and depolymerizes at the nick sites utilizing energy-rich dNTPs. Using an <i>in vitro</i> assay system, we demonstrate that the β-clamp of the <i>Escherichia coli</i> replisome strongly inhibits nick translation on the DNA substrate. To do so, β-clamp inhibits the strand displacement activity of Pol I by interfering with the interaction between the finger subdomain of Pol I and the downstream primer-template junction. Conversely, β-clamp stimulates the 5’ exonuclease property of Pol I to cleave single nucleotides or shorter oligonucleotide flaps. This single nucleotide flap removal at high frequency increases the probability of ligation between the upstream and downstream DNA strands at an early phase, terminating nick translation. Besides β-clamp-mediated ligation helps DNA ligase to seal the nick promptly during the maturation of Okazaki fragments.</p></div

β-clamp inhibits the contact between the 5’end of nicked DNA and Pol-I.

<p><b>(A)</b> Structural model of <i>E</i>. <i>coli</i> Klenow /DNA complex shows that finger domain of Klenow makes a contact with downstream nick site. The model shows that the conserved F771 (in blue surface representation), which participates in the strand displacement, is positioned between the downstream nicked DNA strands. (<b>B)</b> A fraction of BrdU base containing radiolabelled 28 bases oligonucleotide shows a gel shift under the near UV light, suggesting that the oligonucleotide makes cross-linked adduct with Klenow during strand displacement (lane 2). The presence of β-clamp and γ-complex in the absence of ATP (lane 3), or ATP alone (lane 4) also exhibited similar crosslinking adduct. However, β-clamp, γ-complex, and ATP together suppressed the formation of crosslinking product (lane 6), suggesting that loading of the β-clamp on the template blocks the crosslinking. * Represents a minor contaminated band with the custom synthesized 28 bases oligonucleotide.</p

The model showing influence of β-clamp in gap repair.

<p><b>(A)</b> The model shows that Pol I removes downstream oligonucleotide by an active nick translation (red flap). The upcoming ligase molecule may ligate the polymerizing upstream (green) and the depolymerising downstream (red) strands occasionally. (<b>B)</b> The clamp bound Pol I has been shown at the nick site. Passive strand displacement for shorter stretch of nucleotides is shown (short red flap). We hypothesize that efficient flap removal of clamp-bound Pol I frequently creates new nick sites. As a result, upcoming ligase molecule may have plenty of time to ligate polymerizing upstream (green) and depolymerising downstream (red) DNA strands at an early stage.</p

EGR4 is critical for cell-fate determination and phenotypic maintenance of geniculate ganglion neurons underlying sweet and umami taste

The sense of taste starts with activation of receptor cells in taste buds by chemical stimuli which then communicate this signal via innervating oral sensory neurons to the CNS. The cell bodies of oral sensory neurons reside in the geniculate ganglion (GG) and nodose/petrosal/jugular ganglion. The geniculate ganglion contains two main neuronal populations: BRN3A+ somatosensory neurons that innervate the pinna and PHOX2B+ sensory neurons that innervate the oral cavity. While much is known about the different taste bud cell subtypes, considerably less is known about the molecular identities of PHOX2B+ sensory subpopulations. In the GG, as many as 12 different subpopulations have been predicted from electrophysiological studies, while transcriptional identities exist for only 3 to 6. Importantly, the cell fate pathways that diversify PHOX2B+ oral sensory neurons into these subpopulations are unknown. The transcription factor EGR4 was identified as being highly expressed in GG neurons. EGR4 deletion causes GG oral sensory neurons to lose their expression of PHOX2B and other oral sensory genes and up-regulate BRN3A. This is followed by a loss of chemosensory innervation of taste buds, a loss of type II taste cells responsive to bitter, sweet, and umami stimuli, and a concomitant increase in type I glial-like taste bud cells. These deficits culminate in a loss of nerve responses to sweet and umami taste qualities. Taken together, we identify a critical role of EGR4 in cell fate specification and maintenance of subpopulations of GG neurons, which in turn maintain the appropriate sweet and umami taste receptor cells

A subset of broadly responsive Type III taste cells contribute to the detection of bitter, sweet and umami stimuli.

Taste receptor cells use multiple signaling pathways to detect chemicals in potential food items. These cells are functionally grouped into different types: Type I cells act as support cells and have glial-like properties; Type II cells detect bitter, sweet, and umami taste stimuli; and Type III cells detect sour and salty stimuli. We have identified a new population of taste cells that are broadly tuned to multiple taste stimuli including bitter, sweet, sour, and umami. The goal of this study was to characterize these broadly responsive (BR) taste cells. We used an IP3R3-KO mouse (does not release calcium (Ca2+) from internal stores in Type II cells when stimulated with bitter, sweet, or umami stimuli) to characterize the BR cells without any potentially confounding input from Type II cells. Using live cell Ca2+ imaging in isolated taste cells from the IP3R3-KO mouse, we found that BR cells are a subset of Type III cells that respond to sour stimuli but also use a PLCβ signaling pathway to respond to bitter, sweet, and umami stimuli. Unlike Type II cells, individual BR cells are broadly tuned and respond to multiple stimuli across different taste modalities. Live cell imaging in a PLCβ3-KO mouse confirmed that BR cells use this signaling pathway to respond to bitter, sweet, and umami stimuli. Short term behavioral assays revealed that BR cells make significant contributions to taste driven behaviors and found that loss of either PLCβ3 in BR cells or IP3R3 in Type II cells caused similar behavioral deficits to bitter, sweet, and umami stimuli. Analysis of c-Fos activity in the nucleus of the solitary tract (NTS) also demonstrated that functional Type II and BR cells are required for normal stimulus induced expression