TY - JOUR
AB - Genetically encoded fluorescent probes of neural activity represent new promising tools for systems neuroscience. Here, we present a comparative in vivo analysis of 10 different genetically encoded calcium indicators, as well as the pH-sensitive synapto-pHluorin. We analyzed their fluorescence changes in presynaptic boutons of the Drosophila larval neuromuscular junction. Robust neural activity did not result in any or noteworthy fluorescence changes when Flash-Pericam, Camgaroo-1, and Camgaroo-2 were expressed. However, calculated on the raw data, fractional fluorescence changes up to 18% were reported by synapto-pHluorin, Yellow Cameleon 2.0, 2.3, and 3.3, Inverse-Pericam, GCaMP1.3, GCaMP1.6, and the troponin C-based calcium sensor TN-L15. The response characteristics of all of these indicators differed considerably from each other, with GCaMP1.6 reporting high rates of neural activity with the largest and fastest fluorescence changes. However, GCaMP1.6 suffered from photobleaching, whereas the fluorescence signals of the double-chromophore indicators were in general smaller but more photostable and reproducible, with TN-L15 showing the fastest rise of the signals at lower activity rates. We show for GCaMP1.3 and YC3.3 that an expanded range of neural activity evoked fairly linear fluorescence changes and a corresponding linear increase in the signal-to-noise ratio (SNR). The expression level of the indicator biased the signal kinetics and SNR, whereas the signal amplitude was independent. The presented data will be useful for in vivo experiments with respect to the selection of an appropriate indicator, as well as for the correct interpretation of the optical signals.
AU - Reiff, Dierk F
AU - Ihring, Alexandra
AU - Guerrero, Giovanna
AU - Isacoff, Ehud Y
AU - Maximilian Jösch
AU - Nakai, Junichi
AU - Borst, Alexander
ID - 1298
IS - 19
JF - Journal of Neuroscience
TI - In vivo performance of genetically encoded indicators of neural activity in flies
VL - 25
ER -
TY - CHAP
AB - The paper surveys the mirror symmetry conjectures of Hausel-Thaddeus and Hausel-Rodriguez-Villegas concerning the equality of certain Hodge numbers of SL(n, ℂ) vs. PGL(n, ℂ) flat connections and character varieties for curves, respectively. Several new results and conjectures and their relations to works of Hitchin, Gothen, Garsia-Haiman and Earl-Kirwan are explained. These use the representation theory of finite groups of Lie-type via the arithmetic of character varieties and lead to an unexpected conjecture for a Hard Lefschetz theorem for their cohomology.
AU - Tamas Hausel
ID - 1444
T2 - Geometric Methods in Algebra and Number Theory
TI - Mirror symmetry and Langlands duality in the non-Abelian Hodge theory of a curve
VL - 235
ER -
TY - JOUR
AB - Building on a recent paper [8], here we argue that the combinatorics of matroids are intimately related to the geometry and topology of toric hyperkähler varieties. We show that just like toric varieties occupy a central role in Stanley’s proof for the necessity of McMullen’s conjecture (or g-inequalities) about the classification of face vectors of simplicial polytopes, the topology of toric hyperkähler varieties leads to new restrictions on face vectors of matroid complexes. Namely in this paper we will give two proofs that the injectivity part of the Hard Lefschetz theorem survives for toric hyperkähler varieties. We explain how this implies the g-inequalities for rationally representable matroids. We show how the geometrical intuition in the first proof, coupled with results of Chari [3], leads to a proof of the g-inequalities for general matroid complexes, which is a recent result of Swartz [20]. The geometrical idea in the second proof will show that a pure O-sequence should satisfy the g-inequalities, thus showing that our result is in fact a consequence of a long-standing conjecture of Stanley.
AU - Tamas Hausel
ID - 1447
IS - 1
JF - Open Mathematics
TI - Quaternionic geometry of matroids
VL - 3
ER -
TY - JOUR
AB - We study an integration theory in circle equivariant cohomology in order to prove a theorem relating the cohomology ring of a hyperkähler quotient to the cohomology ring of the quotient by a maximal abelian subgroup, analogous to a theorem of Martin for symplectic quotients. We discuss applications of this theorem to quiver varieties, and compute as an example the ordinary and equivariant cohomology rings of a hyperpolygon space.
AU - Tamas Hausel
AU - Proudfoot, Nicholas J
ID - 1463
IS - 1
JF - Topology
TI - Abelianization for hyperkähler quotients
VL - 44
ER -
TY - JOUR
AB - Amino acid composition of proteins varies substantially between taxa and, thus, can evolve. For example, proteins from organisms with (G+C)-rich (or (A+T)-rich) genomes contain more (or fewer) amino acids encoded by (G+C)-rich codons. However, no universal trends in ongoing changes of amino acid frequencies have been reported. We compared sets of orthologous proteins encoded by triplets of closely related genomes from 15 taxa representing all three domains of life (Bacteria, Archaea and Eukaryota), and used phylogenies to polarize amino acid substitutions. Cys, Met, His, Ser and Phe accrue in at least 14 taxa, whereas Pro, Ala, Glu and Gly are consistently lost. The same nine amino acids are currently accrued or lost in human proteins, as shown by analysis of non-synonymous single-nucleotide polymorphisms. All amino acids with declining frequencies are thought to be among the first incorporated into the genetic code; conversely, all amino acids with increasing frequencies, except Ser, were probably recruited late. Thus, expansion of initially under-represented amino acids, which began over 3,400 million years ago, apparently continues to this day.
AU - Jordan, Ingo K
AU - Fyodor Kondrashov
AU - Adzhubeǐ, Ivan A
AU - Wolf, Yuri I
AU - Koonin, Eugene V
AU - Kondrashov, Alexey S
AU - Sunyaev, Shamil R
ID - 893
IS - 7026
JF - Nature
TI - A universal trend of amino acid gain and loss in protein evolution
VL - 433
ER -
TY - JOUR
AU - Guzmán, José
AU - Gerevich, Zoltan
AU - Hengstler, Jan
AU - Illes, Peter
AU - Kleemann, Werner
ID - 3720
IS - 4
JF - Synapse
TI - P2Y1 receptors inhibit both strength and plasticity of glutamatergic synaptic neurotransmission in the rat prefrontal cortex.
VL - 57
ER -
TY - JOUR
AB - Recent advances in atomic force microscopy allowed globular and membrane proteins to be mechanically unfolded on a single-molecule level. Presented is an extension to the existing force spectroscopy experiments. While unfolding single bacteriorhodopsins from native purple membranes, small oscillation amplitudes (6–9nm) were supplied to the vertical displacement of the cantilever at a frequency of 3kHz. The phase and amplitude response of the cantilever-protein system was converted to reveal the elastic (conservative) and viscous (dissipative) contributions to the unfolding process. The elastic response (stiffness) of the extended parts of the protein were in the range of a few tens pN/nm and could be well described by the derivative of the wormlike chain model. Discrete events in the viscous response coincided with the unfolding of single secondary structure elements and were in the range of 1μNs/m. In addition, these force modulation spectroscopy experiments revealed novel mechanical unfolding intermediates of bacteriorhodopsin. We found that kinks result in a loss of unfolding cooperativity in transmembrane helices. Reconstructing force-distance spectra by the integration of amplitude-distance spectra verified their position, offering a novel approach to detect intermediates during the forced unfolding of single proteins.
AU - Harald Janovjak
AU - Mueller, Daniel J
AU - Humphris, Andrew D
ID - 3721
IS - 2
JF - Biophysical Journal
TI - Molecular force modulation spectroscopy revealing the dynamic response of single bacteriorhodopsins
VL - 88
ER -
TY - JOUR
AB - In an age of increasingly large data sets, investigators in many different disciplines have turned to clustering as a tool for data analysis and exploration. Existing clustering methods, however, typically depend on several nontrivial assumptions about the structure of data. Here, we reformulate the clustering problem from an information theoretic perspective that avoids many of these assumptions. In particular, our formulation obviates the need for defining a cluster "prototype," does not require an a priori similarity metric, is invariant to changes in the representation of the data, and naturally captures nonlinear relations. We apply this approach to different domains and find that it consistently produces clusters that are more coherent than those extracted by existing algorithms. Finally, our approach provides a way of clustering based on collective notions of similarity rather than the traditional pairwise measures.
AU - Slonim,N.
AU - Atwal,G.
AU - Gasper Tkacik
AU - Bialek, William S
ID - 3741
IS - 51
JF - PNAS
TI - Information-based clustering
VL - 102
ER -
TY - GEN
AB - We address the practical problems of estimating the information relations that characterize large networks. Building on methods developed for analysis of the neural code, we show that reliable estimates of mutual information can be obtained with manageable computational effort. The same methods allow estimation of higher order, multi-information terms. These ideas are illustrated by analyses of gene expression, financial markets, and consumer preferences. In each case, information theoretic measures correlate with independent, intuitive measures of the underlying structures in the system.
AU - Slonim,Noam
AU - Atwal,Gurinder S
AU - Gasper Tkacik
AU - Bialek, William S
ID - 3746
T2 - ArXiv
TI - Estimating mutual information and multi-information in large networks
ER -
TY - JOUR
AB - Characterizing the dynamics of specific RNA levels requires real-time RNA profiling in a single cell. We show that the combination of a synthetic modular genetic system with fluorescence correlation spectroscopy allows us to directly measure in real time the activity of any specific promoter in prokaryotes. Using a simple inducible gene expression system, we found that induced RNA levels within a single bacterium of Escherichia coli exhibited a pulsating profile in response to a steady input of inducer. The genetic deletion of an efflux pump system, a key determinant of antibiotic resistance, altered the pulsating transcriptional dynamics and caused overexpression of induced RNA. In contrast with population measurements, real-time RNA profiling permits identifying relationships between genotypes and transcriptional dynamics that are accessible only at the level of the single cell.
AU - Le,Thuc T.
AU - Harlepp, Sébastien
AU - Calin Guet
AU - Dittmar,Kimberly
AU - Emonet,Thierry
AU - Pan,Tao
AU - Cluzel,Philippe
ID - 3753
IS - 26
JF - PNAS
TI - Real-time RNA profiling within a single bacterium
VL - 102
ER -