3,099 research outputs found
Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses
Fasciola hepatica, a global worm parasite of humans and their livestock, regulates host innate immune responses within hours of infection. Host macrophages, essential to the first-line defence mechanisms, are quickly restricted in their ability to initiate a classic protective pro-inflammatory immune response. We found that macrophages from infected animals are enriched with parasite-derived micro(mi)RNAs. The most abundant of these miRNAs, fhe-miR-125b, is released by the parasite via exosomes and is homologous to a mammalian miRNA, hsa-miR-125b, that is known to regulate the activation of pro-inflammatory M1 macrophages. We show that the parasite fhe-miR-125b loads onto the mammalian Argonaut protein (Ago-2) within macrophages during infection and, therefore, propose that it mimics host miR-125b to negatively regulate the production of inflammatory cytokines. The hijacking of the miRNA machinery controlling innate cell function could be a fundamental mechanism by which worm parasites disarm the early immune responses of their host to ensure successful infection
mTCTScan: a comprehensive platform for annotation and prioritization of mutations affecting drug sensitivity in cancers
Cancer therapies have experienced rapid progress in recent years, with a number of novel small-molecule kinase inhibitors and monoclonal antibodies now being widely used to treat various types of human cancers. During cancer treatments, mutations can have important effects on drug sensitivity. However, the relationship between tumor genomic profiles and the effectiveness of cancer drugs remains elusive. We introduce Mutation To Cancer Therapy Scan (mTCTScan) web server (http://jjwanglab.org/mTCTScan) that can systematically analyze mutations affecting cancer drug sensitivity based on individual genomic profiles. The platform was developed by leveraging the latest knowledge on mutation-cancer drug sensitivity associations and the results from large-scale chemical screening using human cancer cell lines. Using an evidence-based scoring scheme based on current integrative evidences, mTCTScan is able to prioritize mutations according to their associations with cancer drugs and preclinical compounds. It can also show related drugs/compounds with sensitivity classification by considering the context of the entire genomic profile. In addition, mTCTScan incorporates comprehensive filtering functions and cancer-related annotations to better interpret mutation effects and their association with cancer drugs. This platform will greatly benefit both researchers and clinicians for interrogating mechanisms of mutation-dependent drug response, which will have a significant impact on cancer precision medicine.published_or_final_versio
Design of low-cost ionic liquids for lignocellulosic biomass pretreatment
The cost of ionic liquids (ILs) is one of the main impediments to IL utilization in the cellulosic biorefinery, especially in the pretreatment step. In this study, a number of ionic liquids were synthesized with the goal of optimizing solvent cost and stability whilst demonstrating promising processing potential. To achieve this, inexpensive feedstocks such as sulfuric acid and simple amines were combined into a range of protic ionic liquids containing the hydrogen sulfate [HSO] anion. The performance of these ionic liquids was compared to a benchmark system containing the IL 1-ethyl-3-methylimidazolium acetate [CCim][OAc]. The highest saccharification yields were observed for the triethylammonium hydrogen sulfate IL, which was 75% as effective as the benchmark system. Techno-economic modeling revealed that this promising and yet to be optimized yield was achieved at a fraction of the processing cost. This study demonstrates that some ILs can compete with the cheapest pretreatment chemicals, such as ammonia, in terms of effectiveness and process cost, removing IL cost as a barrier to the economic viability of IL-based biorefineries
Electric Field-Tuned Topological Phase Transition in Ultra-Thin Na3Bi - Towards a Topological Transistor
The electric field induced quantum phase transition from topological to
conventional insulator has been proposed as the basis of a topological field
effect transistor [1-4]. In this scheme an electric field can switch 'on' the
ballistic flow of charge and spin along dissipationless edges of the
two-dimensional (2D) quantum spin Hall insulator [5-9], and when 'off' is a
conventional insulator with no conductive channels. Such as topological
transistor is promising for low-energy logic circuits [4], which would
necessitate electric field-switched materials with conventional and topological
bandgaps much greater than room temperature, significantly greater than
proposed to date [6-8]. Topological Dirac semimetals(TDS) are promising systems
in which to look for topological field-effect switching, as they lie at the
boundary between conventional and topological phases [3,10-16]. Here we use
scanning probe microscopy/spectroscopy (STM/STS) and angle-resolved
photoelectron spectroscopy (ARPES) to show that mono- and bilayer films of TDS
Na3Bi [3,17] are 2D topological insulators with bulk bandgaps >400 meV in the
absence of electric field. Upon application of electric field by doping with
potassium or by close approach of the STM tip, the bandgap can be completely
closed then re-opened with conventional gap greater than 100 meV. The large
bandgaps in both the conventional and quantum spin Hall phases, much greater
than the thermal energy kT = 25 meV at room temperature, suggest that ultrathin
Na3Bi is suitable for room temperature topological transistor operation
Detection of weak gravitational lensing distortions of distant galaxies by cosmic dark matter at large scales
Most of the matter in the universe is not luminous and can be observed
directly only through its gravitational effect. An emerging technique called
weak gravitational lensing uses background galaxies to reveal the foreground
dark matter distribution on large scales. Light from very distant galaxies
travels to us through many intervening overdensities which gravitationally
distort their apparent shapes. The observed ellipticity pattern of these
distant galaxies thus encodes information about the large-scale structure of
the universe, but attempts to measure this effect have been inconclusive due to
systematic errors. We report the first detection of this ``cosmic shear'' using
145,000 background galaxies to reveal the dark matter distribution on angular
scales up to half a degree in three separate lines of sight. The observed
angular dependence of this effect is consistent with that predicted by two
leading cosmological models, providing new and independent support for these
models.Comment: 18 pages, 5 figures: To appear in Nature. (This replacement fixes tex
errors and typos.
Evolution in the Cluster Early-type Galaxy Size-Surface Brightness Relation at z =~ 1
We investigate the evolution in the distribution of surface brightness, as a
function of size, for elliptical and S0 galaxies in the two clusters RDCS
J1252.9-2927, z=1.237 and RX J0152.7-1357, z=0.837. We use multi-color imaging
with the Advanced Camera for Surveys on the Hubble Space Telescope to determine
these sizes and surface brightnesses. Using three different estimates of the
surface brightnesses, we find that we reliably estimate the surface brightness
for the galaxies in our sample with a scatter of < 0.2 mag and with systematic
shifts of \lesssim 0.05 mag. We construct samples of galaxies with early-type
morphologies in both clusters. For each cluster, we use a magnitude limit in a
band which closely corresponds to the rest-frame B, to magnitude limit of M_B =
-18.8 at z=0, and select only those galaxies within the color-magnitude
sequence of the cluster or by using our spectroscopic redshifts. We measure
evolution in the rest-frame B surface brightness, and find -1.41 \+/- 0.14 mag
from the Coma cluster of galaxies for RDCS J1252.9-2927 and -0.90 \+/- 0.12 mag
of evolution for RX J0152.7-1357, or an average evolution of (-1.13 \+/- 0.15)
z mag. Our statistical errors are dominated by the observed scatter in the
size-surface brightness relation, sigma = 0.42 \+/- 0.05 mag for RX
J0152.7-1357 and sigma = 0.76 \+/- 0.10 mag for RDCS J1252.9-2927. We find no
statistically significant evolution in this scatter, though an increase in the
scatter could be expected. Overall, the pace of luminosity evolution we measure
agrees with that of the Fundamental Plane of early-type galaxies, implying that
the majority of massive early-type galaxies observed at z =~ 1 formed at high
redshifts.Comment: Accepted in ApJ, 16 pages in emulateapj format with 15 eps figures, 6
in colo
Gate-tunable black phosphorus spin valve with nanosecond spin lifetimes
Two-dimensional materials offer new opportunities for both fundamental
science and technological applications, by exploiting the electron spin. While
graphene is very promising for spin communication due to its extraordinary
electron mobility, the lack of a band gap restricts its prospects for
semiconducting spin devices such as spin diodes and bipolar spin transistors.
The recent emergence of 2D semiconductors could help overcome this basic
challenge. In this letter we report the first important step towards making 2D
semiconductor spin devices. We have fabricated a spin valve based on ultra-thin
(5 nm) semiconducting black phosphorus (bP), and established fundamental spin
properties of this spin channel material which supports all electrical spin
injection, transport, precession and detection up to room temperature (RT).
Inserting a few layers of boron nitride between the ferromagnetic electrodes
and bP alleviates the notorious conductivity mismatch problem and allows
efficient electrical spin injection into an n-type bP. In the non-local spin
valve geometry we measure Hanle spin precession and observe spin relaxation
times as high as 4 ns, with spin relaxation lengths exceeding 6 um. Our
experimental results are in a very good agreement with first-principles
calculations and demonstrate that Elliott-Yafet spin relaxation mechanism is
dominant. We also demonstrate that spin transport in ultra-thin bP depends
strongly on the charge carrier concentration, and can be manipulated by the
electric field effect
Gastrointestinal stromal tumor masquerading as a lung neoplasm. A case presentation and literature review
Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal tract. Their incidence in the esophagus is 1%â3%. Never has a GIST been documented to directly invade the lung. We report a primary esophageal GIST with direct invasion into the lung parenchyma, presenting predominantly with respiratory symptoms. We include a retrospective literature review. Although the principle 'common things are common' usually guides our everyday clinical practice, this case emphasizes that rare entities can mimic common pathologies and underlines the importance of having a clearly defined differential diagnostic list which should be meticulously scrutinized
DNA resection in eukaryotes: deciding how to fix the break
DNA double-strand breaks are repaired by different mechanisms, including homologous
recombination and nonhomologous end-joining. DNA-end resection, the first step in
recombination, is a key step that contributes to the choice of DSB repair. Resection, an
evolutionarily conserved process that generates single-stranded DNA, is linked to checkpoint
activation and is critical for survival. Failure to regulate and execute this process results in
defective recombination and can contribute to human disease. Here, I review recent findings on
the mechanisms of resection in eukaryotes, from yeast to vertebrates, provide insights into the
regulatory strategies that control it, and highlight the consequences of both its impairment and its
deregulation
Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K pumps
Peer reviewedPublisher PD
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