bluuebunny/crossref_metadata_2025_split huggingface dataset:
RhoA Interacts with the Fusion Glycoprotein of Respiratory Syncytial Virus and Facilitates Virus-Induced Syncytium Formation
Authors: Pastey Manoj K. , Crowe James E. , Graham Barney S. 
Published: December 2019

ABSTRACTThe fusion glycoprotein (F) of respiratory syncytial virus (RSV), which mediates membrane fusion and virus entry, was shown to bind RhoA, a small GTPase, in yeast two-hybrid interaction studies. The interaction was confirmed in vivo by mammalian two-hybrid assay and in RSV-infected HEp-2 cells by coimmunoprecipitation. Furthermore, the interaction of F with RhoA was confirmed in vitro by enzyme-linked immunosorbent assay and biomolecular interaction analysis. Yeast two-hybrid interaction studies with various deletion mutants of F and with RhoA indicate that the key binding domains of these proteins are contained within, or overlap, amino acids 146 to 155 and 67 to 110, respectively. The biological significance of this interaction was studied in RSV-infected HEp-2 cells that were stably transfected to overexpress RhoA. There was a positive correlation between RhoA expression and RSV syncytium formation, indicating that RhoA can facilitate RSV-induced syncytium formation.
Equine Herpesvirus 1 Gene 12 Can Substitute for vmw65 in the Growth of Herpes Simplex Virus (HSV) Type 1, Allowing the Generation of Optimized Cell Lines for the Propagation of HSV Vectors with Multiple Immediate-Early Gene Defects
Authors: Thomas S. K. , Lilley C. E. , Latchman D. S. , Coffin R. S. 
Published: December 2019

ABSTRACT
Herpes simplex virus (HSV) has often been suggested for development as a vector, particularly for the nervous system. Considerable evidence has shown that for use of HSV as a vector, immediate-early (IE) gene expression must be minimized or abolished, otherwise such vectors are likely to be highly cytotoxic. Mutations of vmw65 which abolish IE promoter transactivating activity may also be included to reduce IE gene expression generally. However, when vmw65 mutations are combined with an IE gene deletion, such viruses are hard to propagate, even on cells which otherwise complement the IE gene deletion effectively. We have found that vmw65 mutants can be effectively grown on cell lines expressing equine herpesvirus 1 gene 12, a non-HSV homologue of vmw65 with little sequence similarity to its HSV counterpart. This prevents repair by homologous recombination of vmw65 mutations in the virus, which would occur if mutations were complemented by vmw65 itself. The gene 12 protein is not packaged into HSV virions, which is important if viruses grown on such cells are to be used as vectors. These results not only further strengthen the evidence for direct functional homology between and similar modes of action of the two proteins but have allowed the generation of gene 12-containing cell lines in which ICP4 and ICP27 expression is induced by virus infection (probably by ICP0) and which give efficient growth of viruses deficient in ICP27, ICP4, and vmw65 (the viruses also have ICP34.5/ORFP deleted). Efficient growth of such viruses has not previously been possible. As these viruses are highly deficient in IE gene expression generally, such virus-cell line combinations may provide an alternative to HSV vectors with deletions of all four of the regulatory IE genes which, for optimal growth, require cell lines containing all four IE genes but which are hard to generate due to the intrinsic cytotoxicity of each of the proteins.
Antibody-Dependent and -Independent Protection following Intranasal Immunization of Mice with Rotavirus Particles
Authors: McNeal Monica M. , Rae Mary N. , Bean Judy A. , Ward Richard L. 
Published: December 2019

ABSTRACTThe ability to elicit protective immune responses after intranasal immunization with rotavirus particles, either with or without the attenuatedEscherichia coliheat-labile enterotoxin LT(R192G) as an adjuvant, was examined in the adult mouse model. BALB/c mice were administered one or two inoculations of psoralen/UV-inactivated, triple-layered (tl) or double-layered (dl) purified rotavirus particles. Four weeks after immunization, mice were challenged with the murine rotavirus strain EDIM, and the shedding of rotavirus antigen was quantified. Rotaviruses used for immunization included EDIM and heterotypic simian (RRV), bovine (WC3), and human (89-12) strains. tl EDIM stimulated both systemic and intestinal rotavirus antibody responses and complete protection with as little as one 1-μg dose. Inclusion of LT(R192G) (10 μg) significantly increased rotavirus antibody responses and reduced antigen concentrations needed for full protection. Both dl EDIM and heterotypic dl and tl particles stimulated protection, but they did so less than tl EDIM at comparable concentrations, either with or without LT(R192G). When B-cell-deficient μMt mice were immunized with tl EDIM particles, protection was reduced to levels similar to those induced with dl EDIM and heterotypic particles in BALB/c mice. However, dl EDIM particles induced similar levels of protection in both mouse strains. The protection stimulated by tl or dl EDIM particles was not diminished by CD8 cell depletion prior to immunization in either strain of mice. These results indicate that tl EDIM induced immunity at least partially through responses to its outer capsid proteins, presumably by stimulation of serotype-specific neutralizing antibody. In contrast, the other particles stimulated protection primarily by an antibody-independent mechanism. Finally, depletion of CD8 cells had no effect on protection by either mechanism.
Human Papillomavirus Type 16 E7 DNA Vaccine: Mutation in the Open Reading Frame of E7 Enhances Specific Cytotoxic T-Lymphocyte Induction and Antitumor Activity
Authors: Shi Wei , Bu Ping , Liu Jianzhong , Polack Axel , Fisher Susan , Qiao Liang 
Published: December 2019

ABSTRACTA human papillomavirus type 16 E7 DNA vaccine with the open reading frame encoding mutations in two zinc-binding motifs expressed a rapidly degraded E7 protein. This vaccine induced a significantly stronger E7-specific cytotoxic T-lymphocyte response and better tumor protection in mice than did a wild-type E7 DNA vaccine expressing a stable E7 protein.
Short-Sequence DNA Repeats in Prokaryotic Genomes
Authors: van Belkum Alex , Scherer Stewart , van Alphen Loek , Verbrugh Henri 
Published: December 2019

SUMMARY

Short-sequence DNA repeat (SSR) loci can be identified in all eukaryotic and many prokaryotic genomes. These loci harbor short or long stretches of repeated nucleotide sequence motifs. DNA sequence motifs in a single locus can be identical and/or heterogeneous. SSRs are encountered in many different branches of the prokaryote kingdom. They are found in genes encoding products as diverse as microbial surface components recognizing adhesive matrix molecules and specific bacterial virulence factors such as lipopolysaccharide-modifying enzymes or adhesins. SSRs enable genetic and consequently phenotypic flexibility. SSRs function at various levels of gene expression regulation. Variations in the number of repeat units per locus or changes in the nature of the individual repeat sequences may result from recombination processes or polymerase inadequacy such as slipped-strand mispairing (SSM), either alone or in combination with DNA repair deficiencies. These rather complex phenomena can occur with relative ease, with SSM approaching a frequency of 10
−4
per bacterial cell division and allowing high-frequency genetic switching. Bacteria use this random strategy to adapt their genetic repertoire in response to selective environmental pressure. SSR-mediated variation has important implications for bacterial pathogenesis and evolutionary fitness. Molecular analysis of changes in SSRs allows epidemiological studies on the spread of pathogenic bacteria. The occurrence, evolution and function of SSRs, and the molecular methods used to analyze them are discussed in the context of responsiveness to environmental factors, bacterial pathogenicity, epidemiology, and the availability of full-genome sequences for increasing numbers of microorganisms, especially those that are medically relevant.
Role of PKA in the Timing of Developmental Events in
Dictyostelium
Cells
Authors: Loomis William F. 
Published: December 2019

SUMMARY
The cyclic AMP (cAMP)-dependent protein kinase, PKA, is dispensable for growth of Dictyostelium cells but plays a variety of crucial roles in development. The catalytic subunit of PKA is inhibited when associated with its regulatory subunit but is activated when cAMP binds to the regulatory subunit. Deletion of pkaR or overexpression of the gene encoding the catalytic subunit, pkaC, results in constitutive activity. Development is independent of cAMP in strains carrying these genetic alterations and proceeds rapidly to the formation of both spores and stalk cells. However, morphogenesis is aberrant in these mutants. In the wild type, PKA activity functions in a circuit that can spontaneously generate pulses of cAMP necessary for long-range aggregation. It is also essential for transcriptional activation of both prespore and prestalk genes during the slug stage. During culmination, PKA functions in both prespore and prestalk cells to regulate the relative timing of terminal differentiation. A positive feedback loop results in the rapid release of a signal peptide, SDF-2, when prestalk cells are exposed to low levels of SDF-2. The signal transduction pathway that mediates the response to SDF-2 in both prestalk and prespore cells involves the two-component system of DhkA and RegA. When the cAMP phosphodiesterase RegA is inhibited, cAMP accumulates and activates PKA, leading to vacuolation of stalk cells and encapsulation of spores. These studies indicate that multiple inputs regulate PKA activity to control the relative timing of differentiations in Dictyostelium.
Cdc42: An Essential Rho-Type GTPase Controlling Eukaryotic Cell Polarity
Authors: Johnson Douglas I. 
Published: December 2019

SUMMARYCdc42p is an essential GTPase that belongs to the Rho/Rac subfamily of Ras-like GTPases. These proteins act as molecular switches by responding to exogenous and/or endogenous signals and relaying those signals to activate downstream components of a biological pathway. The 11 current members ofthe Cdc42p family display between 75 and 100% amino acid identity and are functional as well as structural homologs. Cdc42p transduces signals to the actin cytoskeleton to initiate and maintain polarized gorwth and to mitogen-activated protein morphogenesis. In the budding yeast Saccharomyces cerevisiae, Cdc42p plays an important role in multiple actin-dependent morphogenetic events such as bud emergence, mating-projection formation, and pseudohyphal growth. In mammalian cells, Cdc42p regulates a variety of actin-dependent events and induces the JNK/SAPK protein kinase cascade, which leads to the activation of transcription factors within the nucleus. Cdc42p mediates these processes through interactions with a myriad of downstream effectors, whose number and regulation we are just starting to understand. In addition, Cdc42p has been implicated in a number of human diseases through interactions with its regulators and downstream effectors. While much is known about Cdc42p sturcture and functional interactions, little is known about the mechanism(s) by which it transduces signals within the cell. Future research sould focus on this question as well as on the detailed analysis of the interactions of Cdc42p with its regulators and downstream effectors.
DNA Bending and Wrapping around RNA Polymerase: a “Revolutionary” Model Describing Transcriptional Mechanisms
Authors: Coulombe Benoit , Burton Zachary F. 
Published: December 2019

SUMMARY
A model is proposed in which bending and wrapping of DNA around RNA polymerase causes untwisting of the DNA helix at the RNA polymerase catalytic center to stimulate strand separation prior to initiation. During elongation, DNA bending through the RNA polymerase active site is proposed to lower the energetic barrier to the advance of the transcription bubble. Recent experiments with mammalian RNA polymerase II along with accumulating evidence from studies of Escherichia coli RNA polymerase indicate the importance of DNA bending and wrapping in transcriptional mechanisms. The DNA-wrapping model describes specific roles for general RNA polymerase II transcription factors (TATA-binding protein [TBP], TFIIB, TFIIF, TFIIE, and TFIIH), provides a plausible explanation for preinitiation complex isomerization, suggests mechanisms underlying the synergy between transcriptional activators, and suggests an unforseen role for TBP-associating factors in transcription.
Helicobacter pyloriPhysiology Predicted from Genomic Comparison of Two Strains
Authors: Doig Peter , de Jonge Boudewijn L. , Alm Richard A. , Brown Eric D. , Uria-Nickelsen Maria , Noonan Brian , Mills Scott D. , Tummino Peter , Carmel Gilles , Guild Braydon C. , Moir Donald T. , Vovis Gerald F. , Trust Trevor J. 
Published: December 2019

SUMMARYHelicobacter pylori is a gram-negative bacteria which colonizes the gastric mucosa of humans and is implicated in a wide range of gastroduodenal diseases. This paper reviews the physiology of this bacterium as predicted from the sequenced genomes of two unrelated strains and reconciles these predictions with the literature. In general, the predicted capabilities are in good agreement with reported experimental observations. H. pylori is limited in carbohydrate utilization and will use amino acids, for which it has transporter systems, as sources of carbon. Energy can be generated by fermentation, and the bacterium possesses components necessary for both aerobic and anaerobic respiration. Sulfur metabolism is limited, whereas nitrogen metabolism is extensive. There is active uptake of DNA via transformation and ample restriction-modification activities. The cell contains numerous outer membrane proteins, some of which are porins or involved in iron uptake. Some of these outer membrane proteins and the lipopolysaccharide may be regulated by a slipped-strand repair mechanism which probably results in phase variation and plays a role in colonization. In contrast to a commonly held belief that H. pylori is a very diverse species, few differences were predicted in the physiology of these two unrelated strains, indicating that host and environmental factors probably play a significant role in the outocme of H. pylori-related disease.
Relationship between health literacy and quality of life among cancer survivors in China: a cross-sectional study
Authors: Xia Juan , Wu Peng , Deng Qinglong , Yan Rui , Yang Renren , Lv Binghui , Wang Jiwei , Yu Jinming 
Published: December 2019

ObjectiveTo evaluate the association between health literacy (HL) and quality of life (QOL) among cancer survivors in China.DesignCross-sectional study in China.Setting and participantsThis is a cross-sectional observational study of 4589 cancer survivors aged 18 years and older from the Shanghai Cancer Rehabilitation Club. Participants were enrolled and completed the questionnaires between May and July 2017.MeasurementHL was assessed by three established screening questions and QOL was evaluated using the simplified Chinese version of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 items. Answers to all questionnaires were collected through face-to-face interviews or through self-administered questionnaires for literate participants. Participants were excluded if they did not answer any one of the HL questions. Baseline characteristics were compared by levels of HL using χ2test for categorical variables and Wilcoxon rank-sum test for non-normal continuous variables. The item response theory (IRT) was used to evaluate the existing measure of HL. Linear regression and logistic regression models were used to investigate the association between HL and QOL. SAS V.9.4 and MULTILOG V.7.03 were used in the analysis.ResultsThere were 4589 participants included in the study. The calculated results of IRT scale parameters of HL entries indicate that the entries have better discrimination and difficulty. Of the 4589 respondents, 159 (3.5%) had low HL. After adjusting for sociodemographic characteristics, treatment regimen and years with cancers, for each one-point decrement in HL score the QOL score increased by 2.07 (p<0.001). Cancer survivors with low HL were less likely than those with adequate HL to achieve better QOL. In logistic regression, low HL was independently associated with poor QOL (adjusted OR, 2.81; 95% CI 1.94 to 4.06; p<0.001).ConclusionsLow HL was independently associated with poor QOL among cancer survivors of the Shanghai Cancer Rehabilitation Club.
Digital phenotyping for assessment and prediction of mental health outcomes: a scoping review protocol
Authors: Spinazze Pier , Rykov Yuri , Bottle Alex , Car Josip 
Published: December 2019

IntroductionRapid advancements in technology and the ubiquity of personal mobile digital devices have brought forth innovative methods of acquiring healthcare data. Smartphones can capture vast amounts of data both passively through inbuilt sensors or connected devices and actively via user engagement. This scoping review aims to evaluate evidence to date on the use of passive digital sensing/phenotyping in assessment and prediction of mental health.Methods and analysisThe methodological framework proposed by Arksey and O’Malley will be used to conduct the review following the five-step process. A three-step search strategy will be used: (1) Initial limited search of online databases namely, MEDLINE for literature on digital phenotyping or sensing for key terms; (2) Comprehensive literature search using all identified keywords, across all relevant electronic databases: IEEE Xplore, MEDLINE, the Cochrane Database of Systematic Reviews, PubMed, the ACM Digital Library and Web of Science Core Collection (Science Citation Index Expanded and Social Sciences Citation Index), Scopus and (3) Snowballing approach using the reference and citing lists of all identified key conceptual papers and primary studies. Data will be charted and sorted using a thematic analysis approach.Ethics and disseminationThe findings from this systematic scoping review will be reported at scientific meetings and published in a peer-reviewed journal.
Improving mental health and physiological stress responses in mothers following traumatic childbirth and in their infants: study protocol for the Swiss TrAumatic biRth Trial (START)
Authors: Sandoz Vania , Deforges Camille , Stuijfzand Suzannah , Epiney Manuella , Vial Yvan , Sekarski Nicole , Messerli-Bürgy Nadine , Ehlert Ulrike , Bickle-Graz Myriam , Morisod Harari Mathilde , Porcheret Kate , Schechter Daniel S , Ayers Susan , Holmes Emily A , Horsch Antje 
Published: December 2019

IntroductionEmergency caesarean section (ECS) qualifies as a psychological trauma, which may result in postnatal post-traumatic stress disorder (PTSD). Maternal PTSD may not only have a significant negative impact on mother–infant interactions, but also on long-term infant development. The partner’s mental health may also affect infant development. Evidence-based early interventions to prevent the development of postpartum PTSD in mothers are lacking. Immediately after a traumatic event, memory formation is vulnerable to interference. There is accumulating evidence that a brief behavioural intervention including a visuospatial task may result in a reduction in intrusive memories of the trauma.Methods and analysisThis study protocol describes a double-blind multicentre randomised controlled phase III trial testing an early brief maternal intervention including the computer game ‘Tetris’ on intrusive memories of the ECS trauma (≤1 week) and PTSD symptoms (6 weeks, primary outcome) of 144 women following an ECS. The intervention group will carry out a brief behavioural procedure including playing Tetris. The attention-placebo control group will complete a brief written activity log. Both simple cognitive tasks will be completed within the first 6 hours following traumatic childbirth. The intervention is delivered by midwives/nurses in the maternity unit.The primary outcome will be differences in the presence and severity of maternal PTSD symptoms between the intervention and the attention-placebo control group at 6 weeks post partum. Secondary outcomes will be physiological stress and psychological vulnerability, mother–infant interaction and infant developmental outcomes. Other outcomes will be psychological vulnerability and physiological regulation of the partner and their bonding with the infant, as well as the number of intrusive memories of the event.Ethics and disseminationEthical approval was granted by the Human Research Ethics Committee of the Canton de Vaud (study number 2017–02142). Dissemination of results will occur via national and international conferences, in peer-reviewed journals, public conferences and social media.Trial registration numberNCT 03576586.
Vitamin D in the prevention of exacerbations of asthma in preschoolers (DIVA): protocol for a multicentre randomised placebo-controlled triple-blind trial
Authors: Jensen Megan E , Ducharme Francine M , Alos Nathalie , Mailhot Geneviève , Mâsse Benoît , White John H , Sadatsafavi Mohsen , Khamessan Ali , Tse Sze Man , Alizadehfar Reza , Bock Dirk E , Daigneault Patrick , Lemire Chantal , Yang Connie , Radhakrishnan Dhenuka 
Published: December 2019

IntroductionPreschoolers have the highest rate of emergency visits and hospitalisations for asthma exacerbations of all age groups, with most triggered by upper respiratory tract infections (URTIs) and occurring in the fall or winter. Vitamin D insufficiency is highly prevalent in Canadian preschoolers with recurrent asthma exacerbations, particularly in winter. It is associated with more URTIs and, in patients with asthma, more oral corticosteroid (OCS) use. Although evidence suggests that vitamin D supplements significantly decrease URTIs and asthma exacerbations requiring OCS, there is insufficient data in preschoolers. This study aims to determine the impact of vitamin D3 supplementation on exacerbations requiring OCS, in preschoolers with recurrent URTI-induced asthma exacerbations.Methods and analysisThis is a phase III, randomised, triple-blind, placebo-controlled, parallel-group multicentre trial of vitamin D3 supplementation in children aged 1–5 years, with asthma triggered by URTIs and a recent history of frequent URTIs and OCS use. Children (n=865) will be recruited in the fall and early winter and followed for 7 months. They will be randomised to either the (1) intervention: two oral boluses of 100 000 international unit (IU) vitamin D3 (3.5 months apart) with 400 IU vitamin D3 daily; or (2) control: identical placebo boluses with daily placebo. The primary outcome is the number of exacerbations requiring OCS per child, documented by medical and pharmacy records. Secondary outcomes include number of laboratory-confirmed viral URTIs, exacerbation duration and severity, parent functional status, healthcare use, treatment deintensification, cost and safety.Ethics and disseminationThis study has received ethical approval from all sites. Results will be disseminated via international conferences and manuscripts targeting paediatricians and respirologists, and to families of asthmatic children via our Quebec parents–partners outreach programme. If proven effective, findings may markedly influence the management of URTI-induced asthma in high-morbidity preschoolers and could be directly implemented into practice with an update to clinical guidelines.Trial registration numberNCT03365687.