1,660 research outputs found
PU.1 controls fibroblast polarization and tissue fibrosis
Fibroblasts are polymorphic cells with pleiotropic roles in organ morphogenesis, tissue homeostasis and immune responses. In fibrotic diseases, fibroblasts synthesize abundant amounts of extracellular matrix, which induces scarring and organ failure. By contrast, a hallmark feature of fibroblasts in arthritis is degradation of the extracellular matrix because of the release of metalloproteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms that drive these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts remain unknown. Here we identify the transcription factor PU.1 as an essential regulator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms that normally control the expression of PU.1 expression is perturbed in various fibrotic diseases, resulting in the upregulation of PU.1, induction of fibrosis-associated gene sets and a phenotypic switch in extracellular matrix-producing pro-fibrotic fibroblasts. By contrast, pharmacological and genetic inactivation of PU.1 disrupts the fibrotic network and enables reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs
«ЩОБ ХОЧ НЕ СИДЯЧОГО ТАТАРИ БРАЛИ…»
Одним із вагомих (не в останню чергу з точки зору суспільної ваги) напрямків в колі наукових зацікавлень Ганни Кирилівни є краєзнавство, до якого не завжди «прихильно» ставиться академічна наука. Саме з краєзнавчої актуальності виводить Автор у передмові потребу у написанні роботи, присвяченої досить знаковій постаті на загальноукраїнському тлі і абсолютно виключній особистості на регіональному рівні – Михайлові Федоровичу Комарову (1844-1913) (с.4-5
Distinct switching of chiral transport in the kagome metals KVSb and CsVSb
The kagome metals AVSb (A=K,Rb,Cs) present an ideal sandbox to study
the interrelation between multiple coexisting correlated phases such as charge
order and superconductivity. So far, no consensus on the microscopic nature of
these states has been reached as the proposals struggle to explain all their
exotic physical properties. Among these, field-switchable electric
magneto-chiral anisotropy (eMChA) in CsVSb provides intriguing evidence
for a rewindable electronic chirality, yet the other family members have not
been likewise investigated. Here, we present a comparative study of
magneto-chiral transport between CsVSb and KVSb. Despite their
similar electronic structure, KVSb displays negligible eMChA, if any,
and with no field switchability. This is in stark contrast to the
non-saturating eMChA in CsVSb even in high fields up to 35 T. In light
of their similar band structures, the stark difference in eMChA suggests its
origin in the correlated states. Clearly, the V kagome nets alone are not
sufficient to describe the physics and the interactions with their environment
are crucial in determining the nature of their low-temperature state
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Specific detection of methionine 27 mutation in histone 3 variants (H3K27M) in fixed tissue from high-grade astrocytomas
Studies in pediatric high-grade astrocytomas (HGA) by our group and others have uncovered recurrent somatic mutations affecting highly conserved residues in histone 3 (H3) variants. One of these mutations leads to analogous p.Lys27Met (K27M) mutations in both H3.3 and H3.1 variants, is associated with rapid fatal outcome, and occurs specifically in HGA of the midline in children and young adults. This includes diffuse intrinsic pontine gliomas (80 %) and thalamic or spinal HGA (>90 %), which are surgically challenging locations with often limited tumor material available and critical need for specific histopathological markers. Here, we analyzed formalin-fixed paraffin-embedded tissues from 143 pediatric HGA and 297 other primary brain tumors or normal brain. Immunohistochemical staining for H3K27M was compared to tumor genotype, and also compared to H3 tri-methylated lysine 27 (H3K27me3) staining, previously shown to be drastically decreased in samples carrying this mutation. There was a 100 % concordance between genotype and immunohistochemical analysis of H3K27M in tumor samples. Mutant H3K27M was expressed in the majority of tumor cells, indicating limited intra-tumor heterogeneity for this specific mutation within the limits of our dataset. Both H3.1 and H3.3K27M mutants were recognized by this antibody while non-neoplastic elements, such as endothelial and vascular smooth muscle cells or lymphocytes, did not stain. H3K27me3 immunoreactivity was largely mutually exclusive with H3K27M positivity. These results demonstrate that mutant H3K27M can be specifically identified with high specificity and sensitivity using an H3K27M antibody and immunohistochemistry. Use of this antibody in the clinical setting will prove very useful for diagnosis, especially in the context of small biopsies in challenging midline tumors and will help orient care in the context of the extremely poor prognosis associated with this mutation. Electronic supplementary material The online version of this article (doi:10.1007/s00401-014-1337-4) contains supplementary material, which is available to authorized users
Transit Timing Observations from Kepler: III. Confirmation of 4 Multiple Planet Systems by a Fourier-Domain Study of Anti-correlated Transit Timing Variations
We present a method to confirm the planetary nature of objects in systems
with multiple transiting exoplanet candidates. This method involves a
Fourier-Domain analysis of the deviations in the transit times from a constant
period that result from dynamical interactions within the system. The
combination of observed anti-correlations in the transit times and mass
constraints from dynamical stability allow us to claim the discovery of four
planetary systems Kepler-25, Kepler-26, Kepler-27, and Kepler-28, containing
eight planets and one additional planet candidate.Comment: Accepted to MNRA
Building a Global Ecosystem Research Infrastructure to Address Global Grand Challenges for Macrosystem Ecology
The development of several large-, "continental"-scale ecosystem research infrastructures over recent decades has provided a unique opportunity in the history of ecological science. The Global Ecosystem Research Infrastructure (GERI) is an integrated network of analogous, but independent, site-based ecosystem research infrastructures (ERI) dedicated to better understand the function and change of indicator ecosystems across global biomes. Bringing together these ERIs, harmonizing their respective data and reducing uncertainties enables broader cross-continental ecological research. It will also enhance the research community capabilities to address current and anticipate future global scale ecological challenges. Moreover, increasing the international capabilities of these ERIs goes beyond their original design intent, and is an unexpected added value of these large national investments. Here, we identify specific global grand challenge areas and research trends to advance the ecological frontiers across continents that can be addressed through the federation of these cross-continental-scale ERIs.Peer reviewe
Characterization of addressability by simultaneous randomized benchmarking
The control and handling of errors arising from cross-talk and unwanted
interactions in multi-qubit systems is an important issue in quantum
information processing architectures. We introduce a benchmarking protocol that
provides information about the amount of addressability present in the system
and implement it on coupled superconducting qubits. The protocol consists of
randomized benchmarking each qubit individually and then simultaneously, and
the amount of addressability is related to the difference of the average gate
fidelities of those experiments. We present the results on two similar samples
with different amounts of cross-talk and unwanted interactions, which agree
with predictions based on simple models for the amount of residual coupling.Comment: 5 pages, 4 figure
Large-amplitude driving of a superconducting artificial atom: Interferometry, cooling, and amplitude spectroscopy
Superconducting persistent-current qubits are quantum-coherent artificial
atoms with multiple, tunable energy levels. In the presence of large-amplitude
harmonic excitation, the qubit state can be driven through one or more of the
constituent energy-level avoided crossings. The resulting
Landau-Zener-Stueckelberg (LZS) transitions mediate a rich array of
quantum-coherent phenomena. We review here three experimental works based on
LZS transitions: Mach-Zehnder-type interferometry between repeated LZS
transitions, microwave-induced cooling, and amplitude spectroscopy. These
experiments exhibit a remarkable agreement with theory, and are extensible to
other solid-state and atomic qubit modalities. We anticipate they will find
application to qubit state-preparation and control methods for quantum
information science and technology.Comment: 13 pages, 5 figure
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