Cdc48/p97 Mediates UV-Dependent Turnover of RNA Pol II

Cdc48/p97 is an essential ATPase whose role in targeting substrates to the ubiquitin-proteasome system (UPS) remains unclear. Existing models posit that Cdc48 acts upstream of UPS receptors. To address this hypothesis, we examined the association of ubiquitin (Ub) conjugates with 26S proteasomes. Unexpectedly, proteasomes isolated from cdc48 mutants contain high levels of Ub conjugates, and mass spectrometry identified numerous nonproteasomal proteins, including Rpb1, the largest subunit of RNA Pol II. UV-induced turnover of Rpb1 depends upon Cdc48-Ufd1-Npl4, Ubx4, and the uncharacterized adaptor Ubx5. Ubiquitinated Rpb1, proteasomes, and Cdc48 accumulate on chromatin in UV-treated wild-type cells, and the former two accumulate to higher levels in mutant cells, suggesting that degradation of Rpb1 is facilitated by Cdc48 at sites of stalled transcription. These data reveal an intimate coupling of function between proteasomes and Cdc48 that we suggest is necessary to sustain processive degradation of unstable subunits of some macromolecular protein complexes

A novel SETD2 variant causing global development delay without overgrowth in a Chinese 3-year-old boy

Background: Luscan-Lumish syndrome is characterized by macrocephaly, postnatal overgrowth, intellectual disability (ID), developmental delay (DD), which is caused by heterozygous SETD2 (SET domain containing 2) mutations. The incidence of Luscan-Lumish syndrome is unclear. The study was conducted to provide a novel pathogenic SETD2 variant causing atypical Luscan-Lumish syndrome and review all the published SETD2 mutations and corresponding symptoms, comprehensively understanding the phenotypes and genotypes of SETD2 mutations.Methods: Peripheral blood samples of the proband and his parents were collected for next-generation sequencing including whole-exome sequencing (WES), copy number variation (CNV) detection and mitochondrial DNA sequencing. Identified variant was verified by Sanger sequencing. Conservative analysis and structural analysis were performed to investigate the effect of mutation. Public databases such as PubMed, Clinvar and Human Gene Mutation Database (HGMD) were used to collect all cases with SETD2 mutations.Results: A novel pathogenic SETD2 variant (c.5835_c.5836insAGAA, p. A1946Rfs*2) was identified in a Chinese 3-year-old boy, who had speech and motor delay without overgrowth. Conservative analysis and structural analysis showed that the novel pathogenic variant would loss the conserved domains in the C-terminal region and result in loss of function of SETD2 protein. Frameshift mutations and non-sense mutations account for 68.5% of the total 51 SETD2 point mutations, suggesting that Luscan-Lumish syndrome is likely due to loss of function of SETD2. But we failed to find an association between genotype and phenotype of SETD2 mutations.Conclusion: Our findings expand the genotype-phenotype knowledge of SETD2-associated neurological disorder and provide new evidence for further genetic counselling

Tourism cloud management system: the impact of smart tourism.

This study investigates the possibility of supporting tourists in a foreign land intelligently, by using the Tourism Cloud Management System (TCMS) to enhance and better their tourism experience. Some technologies allow tourists to highlight popular tourist routes and circuits, through the visualisation of data and sensor clustering approaches. With this, a tourist can access the shared data on a specific location to know the sites of famous local attractions, how other tourists feel about them, and how to participate in local festivities through a smart tourism model. This study surveyed the potential of smart tourism among tourists and how such technologies have developed over time, while proposing a TCMS. Its goals were to make physical/paper tickets redundant via the introduction of a mobile app with eTickets that can be validated using camera-based and QR code technologies, and to enhance the transport network using Bluetooth and GPS for real-time identification of tourists' proximity. The results show that a significant number of participants engage in tourist travels, hence the need for smart tourism and tourist management. It was concluded that smart tourism is very appealing to tourists and can improve the appeal of the destination, if smart solutions are implemented. This study gives a first-hand review of the preference of tourists and the potential of smart tourism

Multimodal Predictions of Super-Refractory Status Epilepticus and Outcome in Status Epilepticus Due to Acute Encephalitis

Objective: Status epilepticus (SE) is one of the most critical symptoms of encephalitis. Studies on early predictions of progression to super-refractory status epilepticus (SRSE) and poor outcome in SE due to acute encephalitis are scarce. We aimed to investigate the values of neuroimaging and continuous electroencephalogram (EEG) in the multimodal prediction.Methods: Consecutive patients with convulsive SE due to acute encephalitis were included in this study. Demographics, clinical features, neuro-imaging characteristics, medical interventions, and anti-epileptic treatment responses were collected. All the patients had EEG monitoring for at least 24 h. We determined the early predictors of SRSE and prognostic factors of 3-month outcome using multivariate logistic regression analyses.Results: From March 2008 to February 2018, 570 patients with acute encephalitis were admitted to neurological intensive care unit (N-ICU) of Xijing hospital. Among them, a total of 94 patients with SE were included in this study. The percentage of non-SRSE and SRSE were 76.6 and 23.4%. Cortical or hippocampal abnormality on neuroimaging (p = 0.002, OR 20.55, 95% CI 3.16–133.46) and END-IT score (p < 0.001, OR 4.07, 95% CI 1.91–8.67) were independent predictors of the progression to SRSE. At 3 months after N-ICU discharge, 56 (59.6%) patients attained good outcomes, and 38 (40.4%) patients had poor outcomes. The recurrence of clinical or EEG seizures within 2 h after the infusion rate of a single anesthetic drug >50% proposed maximal dose (p = 0.044, OR 4.52, 95% CI 1.04–19.68), tracheal intubation (p = 0.011, OR 4.99, 95% CI 1.37–11.69) and emergency resuscitation (p = 0.040, OR 9.80, 95% 1.11–86.47) predicted poor functional outcome.Interpretation: Initial neuro-imaging findings assist early identification of the progression to SRSE. Continuous EEG monitoring contributes to outcome prediction in SE due to acute encephalitis

Automatic categorization of diverse experimental information in the bioscience literature

Background: Curation of information from bioscience literature into biological knowledge databases is a crucial way of capturing experimental information in a computable form. During the biocuration process, a critical first step is to identify from all published literature the papers that contain results for a specific data type the curator is interested in annotating. This step normally requires curators to manually examine many papers to ascertain which few contain information of interest and thus, is usually time consuming. We developed an automatic method for identifying papers containing these curation data types among a large pool of published scientific papers based on the machine learning method Support Vector Machine (SVM). This classification system is completely automatic and can be readily applied to diverse experimental data types. It has been in use in production for automatic categorization of 10 different experimental datatypes in the biocuration process at WormBase for the past two years and it is in the process of being adopted in the biocuration process at FlyBase and the Saccharomyces Genome Database (SGD). We anticipate that this method can be readily adopted by various databases in the biocuration community and thereby greatly reducing time spent on an otherwise laborious and demanding task. We also developed a simple, readily automated procedure to utilize training papers of similar data types from different bodies of literature such as C. elegans and D. melanogaster to identify papers with any of these data types for a single database. This approach has great significance because for some data types, especially those of low occurrence, a single corpus often does not have enough training papers to achieve satisfactory performance. Results: We successfully tested the method on ten data types from WormBase, fifteen data types from FlyBase and three data types from Mouse Genomics Informatics (MGI). It is being used in the curation work flow at WormBase for automatic association of newly published papers with ten data types including RNAi, antibody, phenotype, gene regulation, mutant allele sequence, gene expression, gene product interaction, overexpression phenotype, gene interaction, and gene structure correction. Conclusions: Our methods are applicable to a variety of data types with training set containing several hundreds to a few thousand documents. It is completely automatic and, thus can be readily incorporated to different workflow at different literature-based databases. We believe that the work presented here can contribute greatly to the tremendous task of automating the important yet labor-intensive biocuration effort

WormBase 2012: more genomes, more data, new website

Since its release in 2000, WormBase (http://www.wormbase.org) has grown from a small resource focusing on a single species and serving a dedicated research community, to one now spanning 15 species essential to the broader biomedical and agricultural research fields. To enhance the rate of curation, we have automated the identification of key data in the scientific literature and use similar methodology for data extraction. To ease access to the data, we are collaborating with journals to link entities in research publications to their report pages at WormBase. To facilitate discovery, we have added new views of the data, integrated large-scale datasets and expanded descriptions of models for human disease. Finally, we have introduced a dramatic overhaul of the WormBase website for public beta testing. Designed to balance complexity and usability, the new site is species-agnostic, highly customizable, and interactive. Casual users and developers alike will be able to leverage the public RESTful application programming interface (API) to generate custom data mining solutions and extensions to the site. We report on the growth of our database and on our work in keeping pace with the growing demand for data, efforts to anticipate the requirements of users and new collaborations with the larger science community

WormBase: a comprehensive resource for nematode research

WormBase (http://www.wormbase.org) is a central data repository for nematode biology. Initially created as a service to the Caenorhabditis elegans research field, WormBase has evolved into a powerful research tool in its own right. In the past 2 years, we expanded WormBase to include the complete genomic sequence, gene predictions and orthology assignments from a range of related nematodes. This comparative data enrich the C. elegans data with improved gene predictions and a better understanding of gene function. In turn, they bring the wealth of experimental knowledge of C. elegans to other systems of medical and agricultural importance. Here, we describe new species and data types now available at WormBase. In addition, we detail enhancements to our curatorial pipeline and website infrastructure to accommodate new genomes and an extensive user base

Time evolution of the Rabi Hamiltonian from the unexcited vacuum

The Rabi Hamiltonian describes a single mode of electromagnetic radiation interacting with a two-level atom. Using the coupled cluster method, we investigate the time evolution of this system from an initially empty field mode and an unexcited atom. We give results for the atomic inversion and field occupation, and find that the virtual processes cause the field to be squeezed. No anti-bunching occurs.Comment: 25 pages, 8 figures, RevTe

Memristive Characteristics of the Single-Layer P-Type CuAlO₂ and N-Type ZnO Memristors

Memristive behaviors are demonstrated in the single-layer oxide-based devices. The conduction states can be continually modulated with different pulses or voltage sweeps. Here, the p-CuAlO2- and n-ZnO-based memristors show the opposite bias polarity dependence with the help of tip electrode. It is well known that the conductivity of p-type and n-type semiconductor materials has the opposite oxygen concentration dependence. Thus, the memristive behaviors may attribute to the oxygen ion migration in the dielectric layers for the single-layer oxide based memristors. Further, based on the redox, the model of compressing dielectric layer thickness has been proposed to explain the memristive behavior