79 research outputs found
An MLL-Dependent Network Sustains Hematopoiesis
The histone methyltransferase Mixed Lineage Leukemia (MLL) is essential to maintain hematopoietic stem cells and is a leukemia protooncogene. Although clustered homeobox genes are well-characterized targets of MLL and MLL fusion oncoproteins, the range of Mll-regulated genes in normal hematopoietic cells remains unknown. Here, we identify and characterize part of the Mll-dependent transcriptional network in hematopoietic stem cells with an integrated approach by using conditional loss-of-function models, genomewide expression analyses, chromatin immunoprecipitation, and functional rescue assays. The Mll-dependent transcriptional network extends well beyond the previously appreciated Hox targets, is comprised of many characterized regulators of self-renewal, and contains target genes that are both dependent and independent of the MLL cofactor, Menin. Interestingly, PR-domain containing 16 emerged as a target gene that is uniquely effective at partially rescuing Mll-deficient hematopoietic stem and progenitor cells. This work highlights the tissue-specific nature of regulatory networks under the control of MLL/Trithorax family members and provides insight into the distinctions between the participation of MLL in normal hematopoiesis and in leukemia
Co-Transport of Polycyclic Aromatic Hydrocarbons by Motile Microorganisms Leads to Enhanced Mass Transfer under Diffusive Conditions.
The
environmental chemodynamics of hydrophobic organic chemicals
(HOCs) are often rate-limited by diffusion in stagnant boundary layers.
This study investigated whether motile microorganisms can act as microbial
carriers that enhance mass transfer of HOCs through diffusive boundary
layers. A new experimental system was developed that allows (1) generation
of concentration gradients of HOCs under the microscope, (2) exposure
and direct observation of microorganisms in such gradients, and (3)
quantification of HOC mass transfer. Silicone O-rings were integrated
into a Dunn chemotaxis chamber to serve as sink and source for polycyclic
aromatic hydrocarbons (PAHs). This resulted in stable concentration
gradients in water (>24 h). Adding the model organism <i>Tetrahymena
pyriformis</i> to the experimental system enhanced PAH mass transfer
up to hundred-fold (benzoÂ[a]Âpyrene). Increasing mass transfer enhancement
with hydrophobicity indicated PAH co-transport with the motile organisms.
Fluorescence microscopy confirmed such transport. The effective diffusivity
of <i>T. pyriformis</i>, determined by video imaging microscopy,
was found to exceed molecular diffusivities of the PAHs up to four-fold.
Cell-bound PAH fractions were determined to range from 28% (naphthalene)
to 92% (pyrene). Motile microorganisms can therefore function as effective
carriers for HOCs under diffusive conditions and might significantly
enhance mobility and availability of HOCs
Energetic electron precipitation driven by electromagnetic ion cyclotron waves from ELFIN's low altitude perspective
We review comprehensive observations of electromagnetic ion cyclotron (EMIC)
wave-driven energetic electron precipitation using data from the energetic
electron detector on the Electron Losses and Fields InvestigatioN (ELFIN)
mission, two polar-orbiting low-altitude spinning CubeSats, measuring 50-5000
keV electrons with good pitch-angle and energy resolution. EMIC wave-driven
precipitation exhibits a distinct signature in energy-spectrograms of the
precipitating-to-trapped flux ratio: peaks at 0.5 MeV which are abrupt (bursty)
with significant substructure (occasionally down to sub-second timescale).
Multiple ELFIN passes over the same MLT sector allow us to study the spatial
and temporal evolution of the EMIC wave - electron interaction region. Using
two years of ELFIN data, we assemble a statistical database of 50 events of
strong EMIC wave-driven precipitation. Most reside at L=5-7 at dusk, while a
smaller subset exists at L=8-12 at post-midnight. The energies of the
peak-precipitation ratio and of the half-peak precipitation ratio (our proxy
for the minimum resonance energy) exhibit an L-shell dependence in good
agreement with theoretical estimates based on prior statistical observations of
EMIC wave power spectra. The precipitation ratio's spectral shape for the most
intense events has an exponential falloff away from the peak (i.e., on either
side of 1.45 MeV). It too agrees well with quasi-linear diffusion theory based
on prior statistics of wave spectra. Sub-MeV electron precipitation observed
concurrently with strong EMIC wave-driven 1MeV precipitation has a spectral
shape that is consistent with efficient pitch-angle scattering down to 200-300
keV by much less intense higher frequency EMIC waves. These results confirm the
critical role of EMIC waves in driving relativistic electron losses. Nonlinear
effects may abound and require further investigation
The ELFIN mission
The Electron Loss and Fields Investigation with a Spatio-Temporal Ambiguity-Resolving option (ELFIN-STAR, or heretoforth simply: ELFIN) mission comprises two identical 3-Unit (3U) CubeSats on a polar (∼93∘ inclination), nearly circular, low-Earth (∼450 km altitude) orbit. Launched on September 15, 2018, ELFIN is expected to have a >2.5 year lifetime. Its primary science objective is to resolve the mechanism of storm-time relativistic electron precipitation, for which electromagnetic ion cyclotron (EMIC) waves are a prime candidate. From its ionospheric vantage point, ELFIN uses its unique pitch-angle-resolving capability to determine whether measured relativistic electron pitch-angle and energy spectra within the loss cone bear the characteristic signatures of scattering by EMIC waves or whether such scattering may be due to other processes. Pairing identical ELFIN satellites with slowly-variable along-track separation allows disambiguation of spatial and temporal evolution of the precipitation over minutes-to-tens-of-minutes timescales, faster than the orbit period of a single low-altitude satellite (Torbit ∼ 90 min). Each satellite carries an energetic particle detector for electrons (EPDE) that measures 50 keV to 5 MeV electrons with Δ E/E 1 MeV. This broad energy range of precipitation indicates that multiple waves are providing scattering concurrently. Many observed events show significant backscattered fluxes, which in the past were hard to resolve by equatorial spacecraft or non-pitch-angle-resolving ionospheric missions. These observations suggest that the ionosphere plays a significant role in modifying magnetospheric electron fluxes and wave-particle interactions. Routine data captures starting in February 2020 and lasting for at least another year, approximately the remainder of the mission lifetime, are expected to provide a very rich dataset to address questions even beyond the primary mission science objective.Published versio
Identification of molecular signatures specific for distinct cranial sensory ganglia in the developing chick
Background The cranial sensory ganglia represent populations of neurons with distinct functions, or sensory modalities. The production of individual ganglia from distinct neurogenic placodes with different developmental pathways provides a powerful model to investigate the acquisition of specific sensory modalities. To date there is a limited range of gene markers available to examine the molecular pathways underlying this process. Results Transcriptional profiles were generated for populations of differentiated neurons purified from distinct cranial sensory ganglia using microdissection in embryonic chicken followed by FAC-sorting and RNAseq. Whole transcriptome analysis confirmed the division into somato- versus viscerosensory neurons, with additional evidence for subdivision of the somatic class into general and special somatosensory neurons. Cross-comparison of distinct ganglia transcriptomes identified a total of 134 markers, 113 of which are novel, which can be used to distinguish trigeminal, vestibulo-acoustic and epibranchial neuronal populations. In situ hybridisation analysis provided validation for 20/26 tested markers, and showed related expression in the target region of the hindbrain in many cases. Results One hundred thirty-four high-confidence markers have been identified for placode-derived cranial sensory ganglia which can now be used to address the acquisition of specific cranial sensory modalities.</p
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