231 research outputs found
Combinatorial RNA Design: Designability and Structure-Approximating Algorithm
In this work, we consider the Combinatorial RNA Design problem, a minimal
instance of the RNA design problem which aims at finding a sequence that admits
a given target as its unique base pair maximizing structure. We provide
complete characterizations for the structures that can be designed using
restricted alphabets. Under a classic four-letter alphabet, we provide a
complete characterization of designable structures without unpaired bases. When
unpaired bases are allowed, we provide partial characterizations for classes of
designable/undesignable structures, and show that the class of designable
structures is closed under the stutter operation. Membership of a given
structure to any of the classes can be tested in linear time and, for positive
instances, a solution can be found in linear time. Finally, we consider a
structure-approximating version of the problem that allows to extend bands
(helices) and, assuming that the input structure avoids two motifs, we provide
a linear-time algorithm that produces a designable structure with at most twice
more base pairs than the input structure.Comment: CPM - 26th Annual Symposium on Combinatorial Pattern Matching, Jun
2015, Ischia Island, Italy. LNCS, 201
Characterizations of ordered semigroups in terms of (∈, ∈ ∨q)-fuzzy interior ideals
In this paper, we give characterizations of ordered semigroups in terms of (∈, ∈ ∨q)-fuzzy interior ideals. We characterize different classes regular (resp. intra-regular, simple and semisimple) ordered semigroups in terms of (∈, ∈ ∨q)-fuzzy interior ideals (resp. (∈, ∈ ∨q)-fuzzy ideals). In this regard, we prove that in regular (resp. intra-regular and semisimple) ordered semigroups the concept of (∈, ∈ ∨q)-fuzzy ideals and (∈, ∈ ∨q)-fuzzy interior ideals coincide. We prove that an ordered semigroup S is simple if and only if it is (∈, ∈ ∨q)-fuzzy simple. We characterize intra-regular (resp. semisimple) ordered semigroups in terms of (∈, ∈ ∨q)-fuzzy ideals (resp. (∈, ∈ ∨q)-fuzzy interior ideals). Finally, we consider the concept of implication-based fuzzy interior ideals in an ordered semigroup, in particular, the implication operators in Lukasiewicz system of continuous-valued logic are discussed
Massively Parallel RNA Chemical Mapping with a Reduced Bias MAP-seq Protocol
Chemical mapping methods probe RNA structure by revealing and leveraging
correlations of a nucleotide's structural accessibility or flexibility with its
reactivity to various chemical probes. Pioneering work by Lucks and colleagues
has expanded this method to probe hundreds of molecules at once on an Illumina
sequencing platform, obviating the use of slab gels or capillary
electrophoresis on one molecule at a time. Here, we describe optimizations to
this method from our lab, resulting in the MAP-seq protocol (Multiplexed
Accessibility Probing read out through sequencing), version 1.0. The protocol
permits the quantitative probing of thousands of RNAs at once, by several
chemical modification reagents, on the time scale of a day using a table-top
Illumina machine. This method and a software package MAPseeker
(http://simtk.org/home/map_seeker) address several potential sources of bias,
by eliminating PCR steps, improving ligation efficiencies of ssDNA adapters,
and avoiding problematic heuristics in prior algorithms. We hope that the
step-by-step description of MAP-seq 1.0 will help other RNA mapping
laboratories to transition from electrophoretic to next-generation sequencing
methods and to further reduce the turnaround time and any remaining biases of
the protocol.Comment: 22 pages, 5 figure
Proximity-dependent initiation of hybridization chain reaction
Sensitive detection of protein interactions and post-translational modifications of native proteins is a challenge for research and diagnostic purposes. A method for this, which could be used in point-of-care devices and high-throughput screening, should be reliable, cost effective and robust. To achieve this, here we design a method (proxHCR) that combines the need for proximal binding with hybridization chain reaction (HCR) for signal amplification. When two oligonucleotide hairpins conjugated to antibodies bind in close proximity, they can be activated to reveal an initiator sequence. This starts a chain reaction of hybridization events between a pair of fluorophore-labelled oligonucleotide hairpins, generating a fluorescent product. In conclusion, we show the applicability of the proxHCR method for the detection of protein interactions and posttranslational modifications in microscopy and flow cytometry. As no enzymes are needed, proxHCR may be an inexpensive and robust alternative to proximity ligation assays
Investigating the dynamics of surface-immobilized DNA nanomachines
Surface-immobilization of molecules can have a profound influence on their structure, function and dynamics. Toehold-mediated strand displacement is often used in solution to drive synthetic nanomachines made from DNA, but the effects of surface-immobilization on the mechanism and kinetics of this reaction have not yet been fully elucidated. Here we show that the kinetics of strand displacement in surface-immobilized nanomachines are significantly different to those of the solution phase reaction, and we attribute this to the effects of intermolecular interactions within the DNA layer. We demonstrate that the dynamics of strand displacement can be manipulated by changing strand length, concentration and G/C content. By inserting mismatched bases it is also possible to tune the rates of the constituent displacement processes (toehold-binding and branch migration) independently, and information can be encoded in the time-dependence of the overall reaction. Our findings will facilitate the rational design of surface-immobilized dynamic DNA nanomachines, including computing devices and track-based motors
ViennaRNA Package 2.0
<p>Abstract</p> <p>Background</p> <p>Secondary structure forms an important intermediate level of description of nucleic acids that encapsulates the dominating part of the folding energy, is often well conserved in evolution, and is routinely used as a basis to explain experimental findings. Based on carefully measured thermodynamic parameters, exact dynamic programming algorithms can be used to compute ground states, base pairing probabilities, as well as thermodynamic properties.</p> <p>Results</p> <p>The <monospace>ViennaRNA</monospace> Package has been a widely used compilation of RNA secondary structure related computer programs for nearly two decades. Major changes in the structure of the standard energy model, the <it>Turner 2004 </it>parameters, the pervasive use of multi-core CPUs, and an increasing number of algorithmic variants prompted a major technical overhaul of both the underlying <monospace>RNAlib</monospace> and the interactive user programs. New features include an expanded repertoire of tools to assess RNA-RNA interactions and restricted ensembles of structures, additional output information such as <it>centroid </it>structures and <it>maximum expected accuracy </it>structures derived from base pairing probabilities, or <it>z</it>-<it>scores </it>for locally stable secondary structures, and support for input in <monospace>fasta</monospace> format. Updates were implemented without compromising the computational efficiency of the core algorithms and ensuring compatibility with earlier versions.</p> <p>Conclusions</p> <p>The <monospace>ViennaRNA Package 2.0</monospace>, supporting concurrent computations <monospace>via OpenMP</monospace>, can be downloaded from <url>http://www.tbi.univie.ac.at/RNA</url>.</p
Occlusion of LTP-Like Plasticity in Human Primary Motor Cortex by Action Observation
Passive observation of motor actions induces cortical activity in the primary motor cortex (M1) of the onlooker, which could potentially contribute to motor learning. While recent studies report modulation of motor performance following action observation, the neurophysiological mechanism supporting these behavioral changes remains to be specifically defined. Here, we assessed whether the observation of a repetitive thumb movement – similarly to active motor practice – would inhibit subsequent long-term potentiation-like (LTP) plasticity induced by paired-associative stimulation (PAS). Before undergoing PAS, participants were asked to either 1) perform abductions of the right thumb as fast as possible; 2) passively observe someone else perform thumb abductions; or 3) passively observe a moving dot mimicking thumb movements. Motor evoked potentials (MEP) were used to assess cortical excitability before and after motor practice (or observation) and at two time points following PAS. Results show that, similarly to participants in the motor practice group, individuals observing repeated motor actions showed marked inhibition of PAS-induced LTP, while the “moving dot” group displayed the expected increase in MEP amplitude, despite differences in baseline excitability. Interestingly, LTP occlusion in the action-observation group was present even if no increase in cortical excitability or movement speed was observed following observation. These results suggest that mere observation of repeated hand actions is sufficient to induce LTP, despite the absence of motor learning
Impact of Flavonoids on Cellular and Molecular Mechanisms Underlying Age-Related Cognitive Decline and Neurodegeneration
Purpose of Review This review summarises the most recent evidence regarding the effects of dietary flavonoids on age-related cognitive decline and neurodegenerative diseases. Recent Findings Recent evidence indicates that plant-derived flavonoids may exert powerful actions on mammalian cognition and protect against the development of age-related cognitive decline and pathological neurodegeneration. The neuroprotective effects of flavonoids have been suggested to be due to interactions with the cellular and molecular architecture of brain regions responsible for memory. Summary Mechanisms for the beneficial effects of flavonoids on age-related cognitive decline and dementia are discussed, including modulating signalling pathways critical in controlling synaptic plasticity, reducing neuroinflammation, promoting vascular effects capable of stimulating new nerve cell growth in the hippocampus, bidirectional interactions with gut microbiota and attenuating the extracellular accumulation of pathological proteins. These processes are known to be important in maintaining optimal neuronal function and preventing age-related cognitive decline and neurodegeneration
Dynamic GABAergic afferent modulation of AgRP neurons
Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) promote homeostatic feeding at times of caloric insufficiency, yet they are rapidly suppressed by food-related sensory cues prior to ingestion. Here we identify a highly selective inhibitory afferent to AgRP neurons that serves as a neural determinant of this rapid modulation. Specifically, GABAergic projections arising from the ventral compartment of the dorsomedial nucleus of the hypothalamus (vDMH) contribute to the pre-consummatory modulation of ARCAgRP neurons. In a manner reciprocal to ARCAgRP neurons, ARC-projecting leptin receptor (LepR)-expressing GABAergic DMH neurons exhibit rapid activation upon availability of food that additionally reflects the relative value of the food. Thus, DMHLepR neurons form part of the sensory network that relays real-time information about the nature and availability of food to dynamically modulate ARCAgRP neuron activity and feeding behavior
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