7,522 research outputs found
Local antiferromagnetic exchange and collaborative Fermi surface as key ingredients of high temperature superconductors
Cuprates, ferropnictides and ferrochalcogenides are three classes of
unconventional high-temperature superconductors, who share similar phase
diagrams in which superconductivity develops after a magnetic order is
suppressed, suggesting a strong interplay between superconductivity and
magnetism, although the exact picture of this interplay remains elusive. Here
we show that there is a direct bridge connecting antiferromagnetic exchange
interactions determined in the parent compounds of these materials to the
superconducting gap functions observed in the corresponding superconducting
materials. High superconducting transition temperature is achieved when the
Fermi surface topology matches the form factor of the pairing symmetry favored
by local magnetic exchange interactions. Our result offers a principle guide to
search for new high temperature superconductors.Comment: 12 pages, 5 figures, 1 table, 1 supplementary materia
Magnetism and its microscopic origin in iron-based high-temperature superconductors
High-temperature superconductivity in the iron-based materials emerges from,
or sometimes coexists with, their metallic or insulating parent compound
states. This is surprising since these undoped states display dramatically
different antiferromagnetic (AF) spin arrangements and Nel
temperatures. Although there is general consensus that magnetic interactions
are important for superconductivity, much is still unknown concerning the
microscopic origin of the magnetic states. In this review, progress in this
area is summarized, focusing on recent experimental and theoretical results and
discussing their microscopic implications. It is concluded that the parent
compounds are in a state that is more complex than implied by a simple Fermi
surface nesting scenario, and a dual description including both itinerant and
localized degrees of freedom is needed to properly describe these fascinating
materials.Comment: 14 pages, 4 figures, Review article, accepted for publication in
Nature Physic
Orexin receptors exert a neuroprotective effect in Alzheimer's disease (AD) via heterodimerization with GPR103
Orexins are neuropeptides that regulate the sleep-wake cycle and feeding behaviour. QRFP is a newly discovered neuropeptide which exerts similar orexigenic activity, thus playing an important role in energy homeostasis and regulation of appetite. The exact expression and signalling characteristics and physiological actions of QRFP and its receptor GPR103 are poorly understood. Alzheimerâ €™ s disease (AD) patients experience increased nocturnal activity, excessive daytime sleepiness, and weight loss. We hypothesised therefore that orexins and QRFP might be implicated in the pathophysiology of AD. We report that the down-regulation of hippocampal orexin receptors (OXRs) and GPR103 particularly in the cornu ammonis (CA) subfield from AD patients suffering from early onset familial AD (EOFAD) and late onset familial AD (LOAD). Using an in vitro model we demonstrate that this downregulation is due to to Aβ-plaque formation and tau hyper-phosphorylation. Transcriptomics revealed a neuroprotective role for both orexins and QRFP. Finally we provide conclusive evidence using BRET and FRET that OXRs and GPR103 form functional hetero-dimers to exert their effects involving activation of ERK 1/2. Pharmacological intervention directed at the orexigenic system may prove to be an attractive avenue towards the discovery of novel therapeutics for diseases such as AD and improving neuroprotective signalling pathways
Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation
Acute myeloid leukemia (AML) involves a block in terminal differentiation of
the myeloid lineage and uncontrolled proliferation of a progenitor state. Using
phorbol myristate acetate (PMA), it is possible to overcome this block in THP-1
cells (an M5-AML containing the MLL-MLLT3 fusion), resulting in differentiation
to an adherent monocytic phenotype. As part of FANTOM4, we used microarrays to
identify 23 microRNAs that are regulated by PMA. We identify four PMA-induced
micro- RNAs (mir-155, mir-222, mir-424 and mir-503) that when overexpressed
cause cell-cycle arrest and partial differentiation and when used in
combination induce additional changes not seen by any individual microRNA. We
further characterize these prodifferentiative microRNAs and show that mir-155
and mir-222 induce G2 arrest and apoptosis, respectively. We find mir-424 and
mir-503 are derived from a polycistronic precursor mir-424-503 that is under
repression by the MLL-MLLT3 leukemogenic fusion. Both of these microRNAs
directly target cell-cycle regulators and induce G1 cell-cycle arrest when
overexpressed in THP-1. We also find that the pro-differentiative mir-424 and
mir-503 downregulate the anti-differentiative mir-9 by targeting a site in its
primary transcript. Our study highlights the combinatorial effects of multiple
microRNAs within cellular systems.Comment: 45 pages 5 figure
High rate of multidrug-resistant Enterobacteriaceae carrying ESBL and plasmid-borne AmpC ß-lactamase in a Malaysian community
Daniel Reidpath - ORCID: 0000-0002-8796-0420
https://orcid.org/0000-0002-8796-0420Background: Even though Southeast Asia is generally regarded as the hotspot for antibiotic resistance, there have been limited studies investigating the prevalence of antibiotic resistance among healthy people in the region. We aimed to investigate the prevalence of two ß-lactamase genes, ESBL and plasmid-borne AmpC (pAmpC) among Enterobacteriaceae in a healthy community in Malaysia.
Methods and materials: We collected stool samples and screened for ESBL and pAmpC-producing Enterobacteriaceae using phenotypic and genotypic methods. The susceptibility profile of the isolates towards 13 different antibiotics was observed. Plasmid replicon group, E. coli phylogenetic group and MLST analyses were also conducted to observe the spread pattern of these resistance genes. Risk factors associated with the carriage of ESBL or pAmpC-producing Enterobacteriaceae were then analysed.
Results: ESBL and pAmpC production was observed in 21.6% (95% CI 13.9–28.8%) and 32.1% (95% CI 24.5–38.9%) of the participants, respectively. A high proportion of the isolates (99.9%, 95% CI 98.6–99.9%) were multidrug-resistant regardless of the resistance genes carried. Although E. coli B2:ST131 was detected, there was no dominance of a specific clonal strain. Possession of multiple plasmid groups was common, with incFIB being the most frequently detected type. Mixed effect logistic regression analysis found that ESBL production was associated with having allergy (p = 0.01, OR 3.86, 95% CI 1.32–11.23) and consumption of chicken meat (p = 0.02, OR = 8.66, 95% CI = 1.40–53.29), while consumption of fermented food significantly lowers the risk of colonisation with pAmpC producing Enterobacteriaceae (p = 0.02, OR 0.23, 95% CI = 0.06–0.79).
Conclusion: The high prevalence of ß-lactamase and multidrug resistance suggests that antibiotic resistance is endemic among healthy people in Malaysia.https://doi.org/10.1016/j.ijid.2020.09.078101pubpubSuppl.
Unique reporter-based sensor platforms to monitor signalling in cells
Introduction: In recent years much progress has been made in the development of tools for systems biology to study the levels of mRNA and protein, and their interactions within cells. However, few multiplexed methodologies are available to study cell signalling directly at the transcription factor level.
<p/>Methods: Here we describe a sensitive, plasmid-based RNA reporter methodology to study transcription factor activation in mammalian cells, and apply this technology to profiling 60 transcription factors in parallel. The methodology uses two robust and easily accessible detection platforms; quantitative real-time PCR for quantitative analysis and DNA microarrays for parallel, higher throughput analysis.
<p/>Findings: We test the specificity of the detection platforms with ten inducers and independently validate the transcription factor activation.
<p/>Conclusions: We report a methodology for the multiplexed study of transcription factor activation in mammalian cells that is direct and not theoretically limited by the number of available reporters
The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.
p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate
Factorization and resummation of s-channel single top quark production
In this paper we study the factorization and resummation of s-channel single
top quark production in the Standard Model at both the Tevatron and the LHC. We
show that the production cross section in the threshold limit can be factorized
into a convolution of hard function, soft function and jet function via
soft-collinear-effective-theory (SCET), and resummation can be performed using
renormalization group equation in the momentum space resummation formalism. We
find that in general, the resummation effects enhance the Next-to-Leading-Order
(NLO) cross sections by about at both the Tevatron and the LHC, and
significantly reduce the factorization scale dependence of the total cross
section at the Tevatron, while at the LHC we find that the factorization scale
dependence has not been improved, compared with the NLO results.Comment: 29 pages, 7 figures; version published in JHE
Depth resolved lattice-charge coupling in epitaxial BiFeO3 thin film
For epitaxial films, a critical thickness (t(c)) can create a phenomenological interface between a strained bottom layer and a relaxed top layer. Here, we present an experimental report of how the t(c) in BiFeO3 thin films acts as a boundary to determine the crystalline phase, ferroelectricity, and piezoelectricity in 60 nm thick BiFeO3/SrRuO3/SrTiO3 substrate. We found larger Fe cation displacement of the relaxed layer than that of strained layer. In the time-resolved X-ray microdiffraction analyses, the piezoelectric response of the BiFeO3 film was resolved into a strained layer with an extremely low piezoelectric coefficient of 2.4 pm/V and a relaxed layer with a piezoelectric coefficient of 32 pm/V. The difference in the Fe displacements between the strained and relaxed layers is in good agreement with the differences in the piezoelectric coefficient due to the electromechanical couplingope
The structural basis for selective binding of non-methylated CpG islands by the CFP1 CXXC domain
CFP1 is a CXXC domain-containing protein and an essential component of the SETD1 histone H3K4 methyltransferase complex. CXXC domain proteins direct different chromatin-modifying activities to various chromatin regions. Here, we report crystal structures of the CFP1 CXXC domain in complex with six different CpG DNA sequences. The crescent-shaped CFP1 CXXC domain is wedged into the major groove of the CpG DNA, distorting the B-form DNA, and interacts extensively with the major groove of the DNA. The structures elucidate the molecular mechanism of the non-methylated CpG-binding specificity of the CFP1 CXXC domain. The CpG motif is confined by a tripeptide located in a rigid loop, which only allows the accommodation of the non-methylated CpG dinucleotide. Furthermore, we demonstrate that CFP1 has a preference for a guanosine nucleotide following the CpG motif
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