A Labelled Sequent Calculus for Public Announcement Logic

Public announcement logic(PAL) is an extension of epistemic logic (EL) with some reduction axioms. In this paper, we propose a cut-free labelled sequent calculus for PAL, which is an extension of that for EL with sequent rules adapted from the reduction axioms. This calculus admits cut and allows terminating proof search

A Conditioned Behavioral Paradigm for Assessing Onset and Lasting Tinnitus in Rats

Numerous behavioral paradigms have been developed to assess tinnitus-like behavior in animals. Nevertheless, they are often limited by prolonged training requirements, as well as an inability to simultaneously assess onset and lasting tinnitus behavior, tinnitus pitch or duration, or tinnitus presence without grouping data from multiple animals or testing sessions. To enhance behavioral testing of tinnitus, we developed a conditioned licking suppression paradigm to determine the pitch(s) of both onset and lasting tinnitus-like behavior within individual animals. Rats learned to lick water during broadband or narrowband noises, and to suppress licking to avoid footshocks during silence. After noise exposure, rats significantly increased licking during silent trials, suggesting onset tinnitus-like behavior. Lasting tinnitus-behavior, however, was exhibited in about half of noise-exposed rats through 7 weeks post-exposure tested. Licking activity during narrowband sound trials remained unchanged following noise exposure, while ABR hearing thresholds fully recovered and were comparable between tinnitus(+) and tinnitus(-) rats. To assess another tinnitus inducer, rats were injected with sodium salicylate. They demonstrated high pitch tinnitus-like behavior, but later recovered by 5 days post-injection. Further control studies showed that 1): sham noise-exposed rats tested with footshock did not exhibit tinnitus-like behavior, and 2): noise-exposed or sham rats tested without footshocks showed no fundamental changes in behavior compared to those tested with shocks. Together, these results demonstrate that this paradigm can efficiently test the development of noise- and salicylate-induced tinnitus behavior. The ability to assess tinnitus individually, over time, and without averaging data enables us to realistically address tinnitus in a clinically relevant way. Thus, we believe that this optimized behavioral paradigm will facilitate investigations into the mechanisms of tinnitus and development of effective treatments

The Protein–Protein Interaction Network of Litopenaeus vannamei Haemocytes

Protein–protein interaction networks (PINs) have been constructed in various organisms and utilized to conduct evolutionary analyses and functional predictions. Litopenaeus vannamei is a high-valued commercial aquaculture species with an uncharacterized interactome. With the development of RNA-seq techniques and systems biology, it is possible to obtain genome-wide transcriptional information for L. vannamei and construct a systematic network based on these data. In this work, based on the RNA-seq of haemocytes we constructed the first L. vannamei PIN including 4,858 proteins and 104,187 interactions. The PIN constructed here is the first large-scale PIN for shrimp. The confidence scores of interactions in the PIN were evaluated on the basis of sequence homology and genetic relationships. The immune-specific sub-network was extracted from global PIN, and more than a third of proteins were found in signaling pathways in the sub-network, which indicates an inseparable relationship between signaling processes and immune mechanisms. Six selected signaling pathways were constructed at different age groups based on evolutionary analyses. Furthermore, we showed that the functions of the pathways’ proteins were associated with their evolutionary history based on the evolutionary analyses combining with protein functional analyses. In addition, the functions of 1,955 unclassified proteins which were associated with 3,191 unigenes were assigned using the PIN, which account for approximately 70.3 and 44.9% of the previously unclassified proteins and unigenes in the network, respectively. The annotation of unclassified proteins and unigenes based on the PIN provides new candidates for further functional studies. The immune-specific sub-network and the pathways extracted from the PIN provide a novel information source for studying of immune mechanisms and disease resistances in shrimp

Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models

Hearing loss is a major risk factor for tinnitus, hyperacusis, and central auditory processing disorder. Although recent studies indicate that hearing loss causes neuroinflammation in the auditory pathway, the mechanisms underlying hearing loss-related pathologies are still poorly understood. We examined neuroinflammation in the auditory cortex following noise-induced hearing loss (NIHL) and its role in tinnitus in rodent models. Our results indicate that NIHL is associated with elevated expression of proinflammatory cytokines and microglial activation-two defining features of neuroinflammatory responses-in the primary auditory cortex (AI). Genetic knockout of tumor necrosis factor alpha (TNF-alpha) or pharmacologically blocking TNF-alpha expression prevented neuroinflammation and ameliorated the behavioral phenotype associated with tinnitus in mice with NIHL. Conversely, infusion of TNF-alpha into AI resulted in behavioral signs of tinnitus in both wild-type and TNF-alpha knockout mice with normal hearing. Pharmacological depletion of microglia also prevented tinnitus in mice with NIHL. At the synaptic level, the frequency of miniature excitatory synaptic currents (mEPSCs) increased and that of miniature inhibitory synaptic currents (mIPSCs) decreased in AI pyramidal neurons in animals with NIHL. This excitatory-to-inhibitory synaptic imbalance was completely prevented by pharmacological blockade of TNF-alpha expression. These results implicate neuroinflammation as a therapeutic target for treating tinnitus and other hearing loss-related disorders.National Institute of Health [DC009259, DC014335]; Department of Defense [W81XWH-15-1-0028, W81XWH-15-1-0356, W81XWH-15-1-0357]; Food and Health Bureau of Hong Kong Special Administrative Region Government [04150076]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

TWISTED DWARF1 mediates the action of auxin transport inhibitors on actin cytoskeleton dynamics

Plant growth and architecture is regulated by the polar distribution of the hormone auxin. Polarity and flexibility of this process is provided by constant cycling of auxin transporter vesicles along actin filaments, coordinated by a positive auxin-actin feedback loop. Both polar auxin transport and vesicle cycling are inhibited by synthetic auxin transport inhibitors, such as 1-N-naphthylphthalamic acid (NPA), counteracting the effect of auxin; however, underlying targets and mechanisms are unclear. Using NMR, we map the NPA binding surface on the Arabidopsis thaliana ABCB chaperone TWISTED DWARF1 (TWD1). We identify ACTIN7 as a relevant, although likely indirect, TWD1 interactor, and show TWD1-dependent regulation of actin filament organization and dynamics and that TWD1 is required for NPA-mediated actin cytoskeleton remodeling. The TWD1-ACTIN7 axis controls plasma membrane presence of efflux transporters, and as a consequence act7 and twd1 share developmental and physiological phenotypes indicative of defects in auxin transport. These can be phenocopied by NPA treatment or by chemical actin (de)stabilization. We provide evidence that TWD1 determines downstream locations of auxin efflux transporters by adjusting actin filament debundling and dynamizing processes and mediating NPA action on the latter. This function appears to be evolutionary conserved since TWD1 expression in budding yeast alters actin polarization and cell polarity and provides NPA sensitivity

Neutron Spectroscopy Evidence for a Possible Magnetic-Field-Induced Gapless Quantum-Spin-Liquid Phase in a Kitaev Material α-RuCl3

As one of the most promising Kitaev quantum-spin-liquid (QSL) candidates, α-RuCl3 has received a great deal of attention. However, its ground state exhibits a long-range zigzag magnetic order, which defies the QSL phase. Nevertheless, the magnetic order is fragile and can be completely suppressed by applying an external magnetic field. Here, we explore the evolution of magnetic excitations of α-RuCl3 under an in-plane magnetic field, by carrying out inelastic neutron scattering measurements on high-quality single crystals. Under zero field, there exist spin-wave excitations near the M point and a continuum near the Γ point, which are believed to be associated with the zigzag magnetic order and fractional excitations of the Kitaev QSL state, respectively. By increasing the magnetic field, the spin-wave excitations gradually give way to the continuous excitations. On the verge of the critical field μ0Hc = 7.5 T, the former ones vanish and only the latter ones are left, indicating the emergence of a pure QSL state. By further increasing the field strength, the excitations near the Γ point become more intense. By following the gap evolution of the excitations near the Γ point, we are able to establish a phase diagram composed of three interesting phases, including a gapped zigzag order phase at low fields, possibly gapless QSL phase near μ0Hc, and gapped partially polarized phase at high fields. These results demonstrate that an in-plane magnetic field can drive α-RuCl3 into a long-sought QSL state near the critical field

GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment

Background: Mutations in GJB2 are the most common molecular defects responsible for autosomal recessive nonsyndromic hearing impairment (NSHI). The mutation spectra of this gene vary among different ethnic groups. Methods: In order to understand the spectrum and frequency of GJB2 mutations in the Chinese population, the coding region of the GJB2 gene from 2063 unrelated patients with NSHI was PCR amplified and sequenced. Results: A total of 23 pathogenic mutations were identified. Among them, five (p.W3X, c.99delT, c.155_c.158delTCTG, c.512_c.513insAACG, and p.Y152X) are novel. Three hundred and seven patients carry two confirmed pathogenic mutations, including 178 homozygotes and 129 compound heterozygotes. One hundred twenty five patients carry only one mutant allele. Thus, GJB2 mutations account for 17.9% of the mutant alleles in 2063 NSHI patients. Overall, 92.6% (684/739) of the pathogenic mutations are frame-shift truncation or nonsense mutations. The four prevalent mutations; c.235delC, c.299_c.300delAT, c.176_c.191del16, and c.35delG, account for 88.0% of all mutantalleles identified. The frequency of GJB2 mutations (alleles) varies from 4% to 30.4% among different regions of China. It also varies among different sub-ethnic groups. Conclusion: In some regions of China, testing of the three most common mutations can identify at least one GJB2 mutant allele in all patients. In other regions such as Tibet, the three most common mutations account for only 16% the GJB2 mutant alleles. Thus, in this region, sequencing of GJB2 would be recommended. In addition, the etiology of more than 80% of the mutant alleles for NSHI in China remains to be identified. Analysis of other NSHI related genes will be necessary

The Genome-Scale Integrated Networks in Microorganisms

The genome-scale cellular network has become a necessary tool in the systematic analysis of microbes. In a cell, there are several layers (i.e., types) of the molecular networks, for example, genome-scale metabolic network (GMN), transcriptional regulatory network (TRN), and signal transduction network (STN). It has been realized that the limitation and inaccuracy of the prediction exist just using only a single-layer network. Therefore, the integrated network constructed based on the networks of the three types attracts more interests. The function of a biological process in living cells is usually performed by the interaction of biological components. Therefore, it is necessary to integrate and analyze all the related components at the systems level for the comprehensively and correctly realizing the physiological function in living organisms. In this review, we discussed three representative genome-scale cellular networks: GMN, TRN, and STN, representing different levels (i.e., metabolism, gene regulation, and cellular signaling) of a cell’s activities. Furthermore, we discussed the integration of the networks of the three types. With more understanding on the complexity of microbial cells, the development of integrated network has become an inevitable trend in analyzing genome-scale cellular networks of microorganisms