TurbuStat: Turbulence Statistics in Python

We present TurbuStat (v1.0): a Python package for computing turbulence statistics in spectral-line data cubes. TurbuStat includes implementations of fourteen methods for recovering turbulent properties from observational data. Additional features of the software include: distance metrics for comparing two data sets; a segmented linear model for fitting lines with a break-point; a two-dimensional elliptical power-law model; multi-core fast-fourier-transform support; a suite for producing simulated observations of fractional Brownian Motion fields, including two-dimensional images and optically-thin HI data cubes; and functions for creating realistic world coordinate system information for synthetic observations. This paper summarizes the TurbuStat package and provides representative examples using several different methods. TurbuStat is an open-source package and we welcome community feedback and contributions.Comment: Accepted in AJ. 21 pages, 8 figure

Assessing the Impact of Astrochemistry on Molecular Cloud Turbulence Statistics

We analyze hydrodynamic simulations of turbulent, star-forming molecular clouds that are post-processed with the photo-dissociation region astrochemistry code 3D-PDR. We investigate the sensitivity of 15 commonly applied turbulence statistics to post-processing assumptions, namely variations in gas temperature, abundance and external radiation field. We produce synthetic $^{12}$CO(1-0) and CI($^{3}$P$_{1}$-$^{3}$P$_{0}$) observations and examine how the variations influence the resulting emission distributions. To characterize differences between the datasets, we perform statistical measurements, identify diagnostics sensitive to our chemistry parameters, and quantify the statistic responses by using a variety of distance metrics. We find that multiple turbulent statistics are sensitive not only to the chemical complexity but also to the strength of the background radiation field. The statistics with meaningful responses include principal component analysis, spatial power spectrum and bicoherence. A few of the statistics, such as the velocity coordinate spectrum, are primarily sensitive to the type of tracer being utilized, while others, like the delta-variance, strongly respond to the background radiation field. Collectively, these findings indicate that more realistic chemistry impacts the responses of turbulent statistics and is necessary for accurate statistical comparisons between models and observed molecular clouds.Comment: 27 pages, 21 figures, accepted to Ap

Theta and gamma rhythmic coding through two spike output modes in the hippocampus during spatial navigation

Hippocampal CA1 neurons generate single spikes and stereotyped bursts of spikes. However, it is unclear how individual neurons dynamically switch between these output modes and whether these two spiking outputs relay distinct information. We performed extracellular recordings in spatially navigating rats and cellular voltage imaging and optogenetics in awake mice. We found that spike bursts are preferentially linked to cellular and network theta rhythms (3–12 Hz) and encode an animal's position via theta phase precession, particularly as animals are entering a place field. In contrast, single spikes exhibit additional coupling to gamma rhythms (30–100 Hz), particularly as animals leave a place field. Biophysical modeling suggests that intracellular properties alone are sufficient to explain the observed input frequency-dependent spike coding. Thus, hippocampal neurons regulate the generation of bursts and single spikes according to frequency-specific network and intracellular dynamics, suggesting that these spiking modes perform distinct computations to support spatial behavior.Fil: Lowet, Eric. Boston University; Estados UnidosFil: Sheehan, Daniel J.. Boston University; Estados UnidosFil: Chialva, Ulises. Universidad Nacional del Sur. Departamento de Matemática; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; ArgentinaFil: De Oliveira Pena, Rodrigo. New Jersey Institute of Technology; Estados UnidosFil: Mount, Rebecca A.. Boston University; Estados UnidosFil: Xiao, Sheng. Boston University; Estados UnidosFil: Zhou, Samuel L.. Boston University; Estados UnidosFil: Tseng, Hua-an. Boston University; Estados UnidosFil: Gritton, Howard. University of Illinois. Urbana - Champaign; Estados UnidosFil: Shroff, Sanaya. Boston University; Estados UnidosFil: Kondabolu, Krishnakanth. Boston University; Estados UnidosFil: Cheung, Cyrus. Boston University; Estados UnidosFil: Wang, Yangyang. Boston University; Estados UnidosFil: Piatkevich, Kiryl D.. Westlake University; ChinaFil: Boyden, Edward S.. McGovern Institute for Brain Research; Estados Unidos. Massachusetts Institute of Technology; Estados UnidosFil: Mertz, Jerome. Boston University; Estados UnidosFil: Hasselmo, Michael E.. Boston University; Estados UnidosFil: Rotstein, Horacio. New Jersey Institute of Technology; Estados UnidosFil: Han, Xue. Boston University; Estados Unido

Optogenetic control of Drosophila using a red-shifted channelrhodopsin reveals experience-dependent influences on courtship

Optogenetics allows the manipulation of neural activity in freely moving animals with millisecond precision, but its application in Drosophila melanogaster has been limited. Here we show that a recently described red activatable channelrhodopsin (ReaChR) permits control of complex behavior in freely moving adult flies, at wavelengths that are not thought to interfere with normal visual function. This tool affords the opportunity to control neural activity over a broad dynamic range of stimulation intensities. Using time-resolved activation, we show that the neural control of male courtship song can be separated into (i) probabilistic, persistent and (ii) deterministic, command-like components. The former, but not the latter, neurons are subject to functional modulation by social experience, which supports the idea that they constitute a locus of state-dependent influence. This separation is not evident using thermogenetic tools, a result underscoring the importance of temporally precise control of neuronal activation in the functional dissection of neural circuits in Drosophila

Loss-of-Function Mutations in PTPN11 Cause Metachondromatosis, but Not Ollier Disease or Maffucci Syndrome

Metachondromatosis (MC) is a rare, autosomal dominant, incompletely penetrant combined exostosis and enchondromatosis tumor syndrome. MC is clinically distinct from other multiple exostosis or multiple enchondromatosis syndromes and is unlinked to EXT1 and EXT2, the genes responsible for autosomal dominant multiple osteochondromas (MO). To identify a gene for MC, we performed linkage analysis with high-density SNP arrays in a single family, used a targeted array to capture exons and promoter sequences from the linked interval in 16 participants from 11 MC families, and sequenced the captured DNA using high-throughput parallel sequencing technologies. DNA capture and parallel sequencing identified heterozygous putative loss-of-function mutations in PTPN11 in 4 of the 11 families. Sanger sequence analysis of PTPN11 coding regions in a total of 17 MC families identified mutations in 10 of them (5 frameshift, 2 nonsense, and 3 splice-site mutations). Copy number analysis of sequencing reads from a second targeted capture that included the entire PTPN11 gene identified an additional family with a 15 kb deletion spanning exon 7 of PTPN11. Microdissected MC lesions from two patients with PTPN11 mutations demonstrated loss-of-heterozygosity for the wild-type allele. We next sequenced PTPN11 in DNA samples from 54 patients with the multiple enchondromatosis disorders Ollier disease or Maffucci syndrome, but found no coding sequence PTPN11 mutations. We conclude that heterozygous loss-of-function mutations in PTPN11 are a frequent cause of MC, that lesions in patients with MC appear to arise following a “second hit,” that MC may be locus heterogeneous since 1 familial and 5 sporadically occurring cases lacked obvious disease-causing PTPN11 mutations, and that PTPN11 mutations are not a common cause of Ollier disease or Maffucci syndrome

Anthrax Lethal Toxin Triggers the Formation of a Membrane-Associated Inflammasome Complex in Murine Macrophages▿

Multiple microbial components trigger the formation of an inflammasome complex that contains pathogen-specific nucleotide oligomerization and binding domain (NOD)-like receptors (NLRs), caspase-1, and in some cases the scaffolding protein ASC. The NLR protein Nalp1b has been linked to anthrax lethal toxin (LT)-mediated cytolysis of murine macrophages. Here we demonstrate that in unstimulated J774A.1 macrophages, caspase-1 and Nalp1b are membrane associated and part of ∼200- and ∼800-kDa complexes, respectively. LT treatment of these cells resulted in caspase-1 recruitment to the Nalp1b-containing complex, concurrent with processing of cytosolic caspase-1 substrates. We further demonstrated that Nalp1b and caspase-1 are able to interact with each other. Intriguingly, both caspase-1 and Nalp1b were membrane associated, while the caspase-1 substrate interleukin-18 was cytosolic. Caspase-1-associated inflammasome components included, besides Nalp1b, proinflammatory caspase-11 and the caspase-1 substrate α-enolase. Asc was not part of the Nalp1b inflammasome in LT-treated macrophages. Taken together, our findings suggest that LT triggers the formation of a membrane-associated inflammasome complex in murine macrophages, resulting in cleavage of cytosolic caspase-1 substrates and cell death

Lethal skeletal dysplasia in mice and humans lacking the golgin GMAP-210.

Establishing the genetic basis of phenotypes such as skeletal dysplasia in model organisms can provide insights into biologic processes and their role in human disease. We screened mutagenized mice and observed a neonatal lethal skeletal dysplasia with an autosomal recessive pattern of inheritance. Through genetic mapping and positional cloning, we identified the causative mutation. Affected mice had a nonsense mutation in the thyroid hormone receptor interactor 11 gene (Trip11), which encodes the Golgi microtubule-associated protein 210 (GMAP-210); the affected mice lacked this protein. Golgi architecture was disturbed in multiple tissues, including cartilage. Skeletal development was severely impaired, with chondrocytes showing swelling and stress in the endoplasmic reticulum, abnormal cellular differentiation, and increased cell death. Golgi-mediated glycosylation events were altered in fibroblasts and chondrocytes lacking GMAP-210, and these chondrocytes had intracellular accumulation of perlecan, an extracellular matrix protein, but not of type II collagen or aggrecan, two other extracellular matrix proteins. The similarities between the skeletal and cellular phenotypes in these mice and those in patients with achondrogenesis type 1A, a neonatal lethal form of skeletal dysplasia in humans, suggested that achondrogenesis type 1A may be caused by GMAP-210 deficiency. Sequence analysis revealed loss-of-function mutations in the 10 unrelated patients with achondrogenesis type 1A whom we studied. GMAP-210 is required for the efficient glycosylation and cellular transport of multiple proteins. The identification of a mutation affecting GMAP-210 in mice, and then in humans, as the cause of a lethal skeletal dysplasia underscores the value of screening for abnormal phenotypes in model organisms and identifying the causative mutations

A genetically encoded near-infrared fluorescent calcium ion indicator

© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. We report an intensiometric, near-infrared fluorescent, genetically encoded calcium ion (Ca2+) indicator (GECI) with excitation and emission maxima at 678 and 704 nm, respectively. This GECI, designated NIR-GECO1, enables imaging of Ca2+ transients in cultured mammalian cells and brain tissue with sensitivity comparable to that of currently available visible-wavelength GECIs. We demonstrate that NIR-GECO1 opens up new vistas for multicolor Ca2+ imaging in combination with other optogenetic indicators and actuators