5,741 research outputs found
Projected entangled-pair states can describe chiral topological states
We show that Projected Entangled-Pair States (PEPS) in two spatial dimensions
can describe chiral topological states by explicitly constructing a family of
such states with a non-trivial Chern number. They are ground states of two
different kinds of free-fermion Hamiltonians: (i) local and gapless; (ii)
gapped, but with hopping amplitudes that decay according to a power law. We
derive general conditions on topological free fermionic PEPS which show that
they cannot correspond to exact ground states of gapped, local parent
Hamiltonians, and provide numerical evidence demonstrating that they can
nevertheless approximate well the physical properties of topological insulators
with local Hamiltonians at arbitrary temperatures.Comment: v2: minor changes, references added. v3: accepted version,
Journal-Ref adde
Molecular principles underlying dual RNA specificity in the Drosophila SNF protein
The first RNA recognition motif of the Drosophila SNF protein is an example of an RNA binding protein with multi-specificity. It binds different RNA hairpin loops in spliceosomal U1 or U2 small nuclear RNAs, and only in the latter case requires the auxiliary U2A′ protein. Here we investigate its functions by crystal structures of SNF alone and bound to U1 stem-loop II, U2A′ or U2 stem-loop IV and U2A′, SNF dynamics from NMR spectroscopy, and structure-guided mutagenesis in binding studies. We find that different loop-closing base pairs and a nucleotide exchange at the tips of the loops contribute to differential SNF affinity for the RNAs. U2A′ immobilizes SNF and RNA residues to restore U2 stem-loop IV binding affinity, while U1 stem-loop II binding does not require such adjustments. Our findings show how U2A′ can modulate RNA specificity of SNF without changing SNF conformation or relying on direct RNA contacts
Matrix Product States with long-range Localizable Entanglement
We derive a criterion to determine when a translationally invariant matrix
product state (MPS) has long-range localizable entanglement, where that
quantity remains finite in the thermodynamic limit. We give examples fulfilling
this criterion and eventually use it to obtain all such MPS with bond dimension
2 and 3.Comment: 8 pages, 1 figur
The intrinsically disordered TSSC4 protein acts as a helicase inhibitor, placeholder and multi-interaction coordinator during snRNP assembly and recycling
Biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) and their recycling after splicing require numerous assembly/recycling factors whose modes of action are often poorly understood. The intrinsically disordered TSSC4 protein has been identified as a nuclear-localized U5 snRNP and U4/U6-U5 tri-snRNP assembly/recycling factor, but how TSSC4's intrinsic disorder supports TSSC4 functions remains unknown. Using diverse interaction assays and cryogenic electron microscopy-based structural analysis, we show that TSSC4 employs four conserved, non-contiguous regions to bind the PRPF8 Jab1/MPN domain and the SNRNP200 helicase at functionally important sites. It thereby inhibits SNRNP200 helicase activity, spatially aligns the proteins, coordinates formation of a U5 sub-module and transiently blocks premature interaction of SNRNP200 with at least three other spliceosomal factors. Guided by the structure, we designed a TSSC4 variant that lacks stable binding to the PRPF8 Jab1/MPN domain or SNRNP200 in vitro. Comparative immunoprecipitation/mass spectrometry from HEK293 nuclear extract revealed distinct interaction profiles of wild type TSSC4 and the variant deficient in PRPF8/SNRNP200 binding with snRNP proteins, other spliceosomal proteins as well as snRNP assembly/recycling factors and chaperones. Our findings elucidate molecular strategies employed by an intrinsically disordered protein to promote snRNP assembly, and suggest multiple TSSC4-dependent stages during snRNP assembly/recycling
Symmetries and boundary theories for chiral Projected Entangled Pair States
We investigate the topological character of lattice chiral Gaussian fermionic
states in two dimensions possessing the simplest descriptions in terms of
projected entangled-pair states (PEPS). They are ground states of two different
kinds of Hamiltonians. The first one, , is local,
frustration-free, and gapless. It can be interpreted as describing a quantum
phase transition between different topological phases. The second one,
is gapped, and has hopping terms scaling as
with the distance . The gap is robust against local perturbations, which
allows us to define a Chern number for the PEPS. As for (non-chiral)
topological PEPS, the non-trivial topological properties can be traced down to
the existence of a symmetry in the virtual modes that are used to build the
state. Based on that symmetry, we construct string-like operators acting on the
virtual modes that can be continuously deformed without changing the state. On
the torus, the symmetry implies that the ground state space of the local parent
Hamiltonian is two-fold degenerate. By adding a string wrapping around the
torus one can change one of the ground states into the other. We use the
special properties of PEPS to build the boundary theory and show how the
symmetry results in the appearance of chiral modes, and a universal correction
to the area law for the zero R\'{e}nyi entropy.Comment: 29 pages, 14 figure
Tinnitus as a Measure of Salicylate Toxicity in the Overdose Setting
Introduction: The development of tinnitus and/or hearing loss (THL) in patients receiving chronic salicylate therapy has been demonstrated. However, to date, little scientific data validates this relationship in the large single overdose setting.Objective: To correlate salicylate levels in patients with the subjective complaint of THL, following an acute salicylate overdose.Methods: A retrospective chart review of cases of acute salicylate toxicity and THL reported to the Illinois Poison Control Center (IPC) from 2001-2002 was performed. Data abstracted included age, gender, ingestion time, salicylate levels, and arterial blood gases.Results: Ninety-nine cases of THL were reviewed and analyzed with mean age of 23.7 years (SD: 10.9), 30.3% male, and 82.2% intentional overdoses. The average dose ingested was 20.0 grams (SD:20.2) and the mean time from ingestion to medical care was 12.4 hours (SD: 11.1). The mean initial ASA level was 48.3 mg/dl (SD: 16.4) with 86.9% having initial level ≥ 30mg/dl and 40.4% ≥ 50 mg/dl. 85.9% of cases presented to the hospital with their ASA level at or past peak. The mean pH was 7.45, pO2 = 108, pCO2 = 28.0, and HCO3 = 19.9.Conclusion: In this limited study, 85.9% of patients presenting with tinnitus and/or hearing loss following a single salicylate ingestion had initial salicylate levels at or past their peak and 86.9% were in the toxic range
A multi-factor trafficking site on the spliceosome remodeling enzyme BRR2 recruits C9ORF78 to regulate alternative splicing
The intrinsically unstructured C9ORF78 protein was detected in spliceosomes but its role in splicing is presently unclear. We find that C9ORF78 tightly interacts with the spliceosome remodeling factor, BRR2, in vitro. Affinity purification/mass spectrometry and RNA UV-crosslinking analyses identify additional C9ORF78 interactors in spliceosomes. Cryogenic electron microscopy structures reveal how C9ORF78 and the spliceosomal B complex protein, FBP21, wrap around the C-terminal helicase cassette of BRR2 in a mutually exclusive manner. Knock-down of C9ORF78 leads to alternative NAGNAG 3′-splice site usage and exon skipping, the latter dependent on BRR2. Inspection of spliceosome structures shows that C9ORF78 could contact several detected spliceosome interactors when bound to BRR2, including the suggested 3′-splice site regulating helicase, PRPF22. Together, our data establish C9ORF78 as a late-stage splicing regulatory protein that takes advantage of a multi-factor trafficking site on BRR2, providing one explanation for suggested roles of BRR2 during splicing catalysis and alternative splicing
Information processing at the foxa node of the sea urchin endomesoderm specification network
The foxa regulatory gene is of central importance for endoderm specification across Bilateria, and this gene lies at an essential node of the well-characterized sea urchin endomesoderm gene regulatory network (GRN). Here we experimentally dissect the cis-regulatory system that controls the complex pattern of foxa expression in these embryos. Four separate cis-regulatory modules (CRMs) cooperate to control foxa expression in different spatial domains of the endomesoderm, and at different times. A detailed mutational analysis revealed the inputs to each of these cis-regulatory modules. The complex and dynamic expression of foxa is regulated by a combination of repressors, a permissive switch, and multiple activators. A mathematical kinetic model was applied to study the dynamic response of foxa cis-regulatory modules to transient inputs. This study shed light on the mesoderm–endoderm fate decision and provides a functional explanation, in terms of the genomic regulatory code, for the spatial and temporal expression of a key developmental control gene
Steps toward translocation-independent RNA polymerase inactivation by terminator ATPase ρ
Factor-dependent transcription termination mechanisms are poorly understood. We determined a series of cryo–electron microscopy structures portraying the hexameric adenosine triphosphatase (ATPase) ρ on a pathway to terminating NusA/NusG-modified elongation complexes. An open ρ ring contacts NusA, NusG, and multiple regions of RNA polymerase, trapping and locally unwinding proximal upstream DNA. NusA wedges into the ρ ring, initially sequestering RNA. Upon deflection of distal upstream DNA over the RNA polymerase zinc-binding domain, NusA rotates underneath one capping ρ subunit, which subsequently captures RNA. After detachment of NusG and clamp opening, RNA polymerase loses its grip on the RNA:DNA hybrid and is inactivated. Our structural and functional analyses suggest that ρ, and other termination factors across life, may use analogous strategies to allosterically trap transcription complexes in a moribund state
Similar temperature dependencies of glycolytic enzymes: an evolutionary adaptation to temperature dynamics?
RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Temperature strongly affects microbial growth, and many microorganisms have to deal with temperature fluctuations in their natural environment. To understand regulation strategies that underlie microbial temperature responses and adaptation, we studied glycolytic pathway kinetics in Saccharomyces cerevisiae during temperature changes. RESULTS: Saccharomyces cerevisiae was grown under different temperature regimes and glucose availability conditions. These included glucose-excess batch cultures at different temperatures and glucose-limited chemostat cultures, subjected to fast linear temperature shifts and circadian sinoidal temperature cycles. An observed temperature-independent relation between intracellular levels of glycolytic metabolites and residual glucose concentration for all experimental conditions revealed that it is the substrate availability rather than temperature that determines intracellular metabolite profiles. This observation corresponded with predictions generated in silico with a kinetic model of yeast glycolysis, when the catalytic capacities of all glycolytic enzymes were set to share the same normalized temperature dependency. CONCLUSIONS: From an evolutionary perspective, such similar temperature dependencies allow cells to adapt more rapidly to temperature changes, because they result in minimal perturbations of intracellular metabolite levels, thus circumventing the need for extensive modification of enzyme levels
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