Gain control in olfactory receptor neurons and the detection of temporal fluctuations in odor concentration

The ability of the cockroach to locate an odor source in still air suggests that the temporal dynamic of odor concentration in the slowly expanding stationary plume alone is used to infer odor source distance and location. This contradicts with the well-established view that insects use the wind direction as the principle directional cue. This contribution highlights the evidence for, and likely functional relevance of, the capacity of the cockroach’s olfactory receptor neurons to detect and process—from one moment to the next—not only a succession of odor concentrations but also the rates at which concentration changes. This presents a challenge for the olfactory system because it must detect and encode the temporal concentration dynamic in a manner that simultaneously allows invariant odor recognition. The challenge is met by a parallel representation of odor identity and concentration changes in a dual pathway that starts from olfactory receptor neurons located in two morphologically distinct types of olfactory sensilla. Parallel processing uses two types of gain control that simultaneously allocate different weight to the instantaneous odor concentration and its rate of change. Robust gain control provides a stable sensitivity for the instantaneous concentration by filtering the information on fluctuations in the rate of change. Variable gain control, in turn, enhances sensitivity for the concentration rate according to variations in the duration of the fluctuation period. This efficiently represents the fluctuation of concentration changes in the environmental context in which such changes occur

Messenger RNA Expression of Selected Factors at Different Sites of the Bovine Endometrium Associated With Uterine Health

Recent studies have elucidated the role of several pro-inflammatory factors as mediators of inflammatory processes in the bovine endometrium. Only few studies, however, have analyzed samples collected from different regions of the uterus of the same animal. In this study, we tested the hypothesis that on a molecular level, clinical endometritis is characterized by inflammatory responses spread over the entire endometrium. Furthermore, we assume that subclinical endometritis is described by an inflammation of local regions of the uterus. Therefore, the objective of this study was to assess the mRNA expression of uterus-associated pro-inflammatory factors at five pre-defined endometrial sites, i.e., corpus uteri, left horn base, left horn tip, right horn base, and right horn tip, in cows with clinical and subclinical endometritis and in healthy controls. We analyzed the mRNA expression of interleukin 1 alpha, interleukin 1 beta, C-X-C motif chemokine ligand 8, prostaglandin-endoperoxide synthase 2, protein tyrosine phosphatase receptor type C, carcinoembryonic antigen related cell adhesion molecule 1, and mucin 4 and 16. Based on vaginoscopy and endometrial cytology (>= 5% polymorphonuclear neutrophils) between 28 to 34 days in milk, 18 Simmental cows were categorized in clinical endometritis group (n = 7), subclinical endometritis group (n = 4), and healthy group (n = 7). In general, the analyses revealed a great variation of mRNA expression between sites and animals. Differences were found between different uterine health statuses, but the variation between the sampling sites within the groups was not significant (P > 0.05). This indicates that inflammatory processes at the end of the postpartum period can be regarded as multi-focal or spread throughout the uterus independent from the uterine health status

Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration

10.7554/eLife.42093.001Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation

A phytochrome sensory domain permits receptor activation by red light

Optogenetics and photopharmacology enable the spatio-temporal control of cell and animal behavior by light. Although red light offers deep-tissue penetration and minimal phototoxicity, very few red-light-sensitive optogenetic methods are currently available. We have now developed a red-light-induced homodimerization domain. We first showed that an optimized sensory domain of the cyanobacterial phytochrome 1 can be expressed robustly and without cytotoxicity in human cells. We then applied this domain to induce the dimerization of two receptor tyrosine kinases—the fibroblast growth factor receptor 1 and the neurotrophin receptor trkB. This new optogenetic method was then used to activate the MAPK/ERK pathway non-invasively in mammalian tissue and in multicolor cell-signaling experiments. The light-controlled dimerizer and red-light-activated receptor tyrosine kinases will prove useful to regulate a variety of cellular processes with light. Go deep with red: The sensory domain (S) of the cyanobacterial phytochrome 1 (CPH1) was repurposed to induce the homodimerization of proteins in living cells by red light. By using this domain, light-activated protein kinases were engineered that can be activated orthogonally from many fluorescent proteins and through mammalian tissue. Pr/Pfr=red-/far-red-absorbing state of CPH1

Reducing orbital eccentricity in binary black hole simulations

Binary black hole simulations starting from quasi-circular (i.e., zero radial velocity) initial data have orbits with small but non-zero orbital eccentricities. In this paper the quasi-equilibrium initial-data method is extended to allow non-zero radial velocities to be specified in binary black hole initial data. New low-eccentricity initial data are obtained by adjusting the orbital frequency and radial velocities to minimize the orbital eccentricity, and the resulting ($\sim 5$ orbit) evolutions are compared with those of quasi-circular initial data. Evolutions of the quasi-circular data clearly show eccentric orbits, with eccentricity that decays over time. The precise decay rate depends on the definition of eccentricity; if defined in terms of variations in the orbital frequency, the decay rate agrees well with the prediction of Peters (1964). The gravitational waveforms, which contain $\sim 8$ cycles in the dominant l=m=2 mode, are largely unaffected by the eccentricity of the quasi-circular initial data. The overlap between the dominant mode in the quasi-circular evolution and the same mode in the low-eccentricity evolution is about 0.99.Comment: 27 pages, 9 figures; various minor clarifications; accepted to the "New Frontiers" special issue of CQ

Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease

Optogenetics has been harnessed to shed new mechanistic light on current and future therapeutic strategies. This has been to date achieved by the regulation of ion flow and electrical signals in neuronal cells and neural circuits that are known to be affected by disease. In contrast, the optogenetic delivery of trophic biochemical signals, which support cell survival and are implicated in degenerative disorders, has never been demonstrated in an animal model of disease. Here, we reengineered the human and Drosophila melanogaster REarranged during Transfection (hRET and dRET) receptors to be activated by light, creating one-component optogenetic tools termed Opto-hRET and Opto-dRET. Upon blue light stimulation, these receptors robustly induced the MAPK/ERK proliferative signaling pathway in cultured cells. In PINK1B9 flies that exhibit loss of PTEN-induced putative kinase 1 (PINK1), a kinase associated with familial Parkinson’s disease (PD), light activation of Opto-dRET suppressed mitochondrial defects, tissue degeneration and behavioral deficits. In human cells with PINK1 loss-of-function, mitochondrial fragmentation was rescued using Opto-dRET via the PI3K/NF-кB pathway. Our results demonstrate that a light-activated receptor can ameliorate disease hallmarks in a genetic model of PD. The optogenetic delivery of trophic signals is cell type-specific and reversible and thus has the potential to inspire novel strategies towards a spatio-temporal regulation of tissue repair

アストロサイトにおける抗うつ薬による塩基性線維芽細胞増殖因子産生機構に関する薬理学的研究

内容の要旨 , 審査の要旨広島大学(Hiroshima University)博士(薬科学)Doctor of Philosophy in Medicinal Sciencedoctora

Initial data for Einstein's equations with superposed gravitational waves

A method is presented to construct initial data for Einstein's equations as a superposition of a gravitational wave perturbation on an arbitrary stationary background spacetime. The method combines the conformal thin sandwich formalism with linear gravitational waves, and allows detailed control over characteristics of the superposed gravitational wave like shape, location and propagation direction. It is furthermore fully covariant with respect to spatial coordinate changes and allows for very large amplitude of the gravitational wave.Comment: Version accepted by PRD; added convergence plots, expanded discussion. 9 pages, 9 figure

Error-analysis and comparison to analytical models of numerical waveforms produced by the NRAR Collaboration

The Numerical-Relativity-Analytical-Relativity (NRAR) collaboration is a joint effort between members of the numerical relativity, analytical relativity and gravitational-wave data analysis communities. The goal of the NRAR collaboration is to produce numerical-relativity simulations of compact binaries and use them to develop accurate analytical templates for the LIGO/Virgo Collaboration to use in detecting gravitational-wave signals and extracting astrophysical information from them. We describe the results of the first stage of the NRAR project, which focused on producing an initial set of numerical waveforms from binary black holes with moderate mass ratios and spins, as well as one non-spinning binary configuration which has a mass ratio of 10. All of the numerical waveforms are analysed in a uniform and consistent manner, with numerical errors evaluated using an analysis code created by members of the NRAR collaboration. We compare previously-calibrated, non-precessing analytical waveforms, notably the effective-one-body (EOB) and phenomenological template families, to the newly-produced numerical waveforms. We find that when the binary's total mass is ~100-200 solar masses, current EOB and phenomenological models of spinning, non-precessing binary waveforms have overlaps above 99% (for advanced LIGO) with all of the non-precessing-binary numerical waveforms with mass ratios <= 4, when maximizing over binary parameters. This implies that the loss of event rate due to modelling error is below 3%. Moreover, the non-spinning EOB waveforms previously calibrated to five non-spinning waveforms with mass ratio smaller than 6 have overlaps above 99.7% with the numerical waveform with a mass ratio of 10, without even maximizing on the binary parameters.Comment: 51 pages, 10 figures; published versio