bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional and LC-MS/MS analysis ofin vitrotranscribed mRNAs carrying phosphorothioate or boranophosphate moieties reveal polyA tail modifications that prevent deadenylation without compromising protein expression
Authors: Strzelecka Dominika , Smietanski Miroslaw , Sikorski Pawel J. , Warminski Marcin , Kowalska Joanna , Jemielity Jacek 
Published: July 2020

ABSTRACTChemical modifications enable preparation of mRNAs with augmented stability and translational activity. In this study, we explored how chemical modifications of 5’,3’-phosphodiester bonds in the mRNA body and polyA tail influence the biological properties of eukaryotic mRNA. To obtain modified and unmodifiedin vitrotranscribed mRNAs, we used ATP and ATP analogues modified at the α-phosphate (containing either O-to-S or O-to-BH3substitutions) and three different RNA polymerases—SP6, T7 and polyA polymerase. To verify the efficiency of incorporation of ATP analogues in the presence of ATP, we developed a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for quantitative assessment of modification frequency based on exhaustive degradation of the transcripts to 5’-mononucleotides. The method also estimated the average polyA tail lengths, thereby providing a versatile tool for establishing a structure-biological property relationship for mRNA. We found that mRNAs containing phosphorothioate groups within the polyA tail were substantially less susceptible to degradation by 3’-deadenylase than unmodified mRNA and were efficiently expressed in cultured cells, which makes them useful research tools and potential candidates for future development of mRNA-based therapeutics.
TheBacillusVirulome in Endophthalmitis
Authors: Coburn Phillip S. , Miller Frederick C. , Enty Morgan A. , Land Craig , LaGrow Austin L. , Mursalin Md Huzzatul , Callegan Michelle C. 
Published: July 2020

AbstractBacillus cereusis recognized as a causative agent of gastrointestinal syndromes, but can also cause a devastating form of intraocular infection known as endophthalmitis. We have previously reported that the PlcR/PapR master virulence factor regulator system regulates intraocular virulence, and that the S-layer protein (SlpA) contributes to the severity ofB. cereusendophthalmitis. To begin to better understand the role of otherB. cereusvirulence genes in endophthalmitis, expression levels of a subset of factors was measured at the midpoint of disease progression in a murine model of experimental endophthalmitis by RNA-Seq. Several cytolytic toxins were expressed at significantly higher levelsin vivothan in BHI. The virulence regulatorscodY, gntR,andnprRwere also expressedin vivo.However, at this timepoint,plcR/papRwas not detectable, we previously reported that aB. cereusmutant deficient in PlcR was attenuated in the eye. The motility-related genesfla, fliF,andmotB,and the chemotaxis-related genecheAwere detected during infection. We have shown previously that motility and chemotaxis phenotypes are important inB. cereusendophthalmitis. ThesodA2variant of manganese superoxide dismutase was the most highly expression genein vivo, suggesting that this gene is criticial for intraocular survival, potentially through inhibition of neutrophil activity. Expression of the surface layer protein gene,slpA,an activator of Toll-like receptors (TLR) −2 and −4, and a potent contributor to intraocular inflammation and disease severvity, was also detected during infection, albeit at low levels. In summary, genes expressed in a mouse model ofBacillusendophthalmitis might prove to play crucial roles in the unique virulence ofB. cereusendophthalmitis, and serve as candidates for novel therapies designed attenuate the severity of this often blinding infection.Impact statementB. cereuscauses a potent and rapid infection of the eye that usually results in blindness or enucleation, even with the utilization of current treatment modalities. This necessitates the development of new treatment modalities based on new targets. To begin to better define thoseB. cereusfactors with roles in intraocular infection, we analyzed the expression of genes with both known and hypothesized roles in intraocular infection at the midpoint of infection using a murine model of Bacillus endophthalmitis. Potentially targetable candidate genes were demonstrated to be expressedin vivo, which suggests that these genes might contribute to the unique virulence ofB. cereusendophthalmitis. Importantly, our results begin to define the virulome ofB. cereusin intraocular infections and identify previously uncharacterized factors with potential roles in the severity and outcome ofBacillusendophthalmitis.
Restrained activation of CYFIP2-containing WAVE complexes controls membrane protrusions and cell migration
Authors: Polesskaya Anna , Boutillon Arthur , Yang Sheng , Wang Yanan , Romero Stéphane , Liu Yijun , Lavielle Marc , Molinie Nicolas , Rocques Nathalie , Fokin Artem , Guérois Raphaël , Chen Baoyu , David Nicolas B. , Gautreau Alexis M. 
Published: July 2020

AbstractBranched actin networks polymerized by the Arp2/3 complex are critical for cell migration. The WAVE complex is the machinery that activates Arp2/3 in a RAC1-dependent manner at the leading edge of migrating cells. Multiple WAVE complexes are assembled in a cell through various combinations of paralogous subunits. Here we report the surprising phenotype associated with loss-of-function of CYFIP2, a subunit of the WAVE complex. In three different human mammary cell lines and in prechordal plate cells of gastrulating zebrafish embryos, CYFIP2 depletion promoted, rather than impaired, membrane protrusions and migration persistence. CYFIP2, however, assembled WAVE complexes that polymerize branched actin at the cell cortex and rescued membrane protrusions ofCYFIP1/2double knock-out cells, although less efficiently than CYFIP1. Point mutations of CYFIP2 associated with intellectual disability in children were gain-of-function, as they made CYFIP2 as active as CYFIP1 in this rescue experiment. Biochemical reconstitutions of CYFIP2-containing WAVE complexes showed that they bound equally well to active RAC1 as CYFIP1-containing WAVE complexes, yet they were poorly activated in response to RAC1 binding. Together these results suggest that CYFIP2-containing WAVE complexes titrate active RAC1 and thereby prevent efficient CYFIP1-containing complexes from being activated. In this context, where cell migration is governed by the balance of CYFIP1/2 expression, releasing the restrained activity of CYFIP2-containing WAVE complexes leads to pathology.
Family Analysis with Mendelian Imputations
Authors: Kong Augustine , Benonisdottir Stefania , Young Alexander I. 
Published: July 2020

AbstractGenotype-phenotype associations can be results of direct effects, genetic nurturing effects and population stratification confounding. Genotypes from parents and siblings of the proband can be used to statistically disentangle these effects. To maximize power, a comprehensive framework for utilizing various combinations of parents’ and siblings’ genotypes is introduced. Central to the approach ismendelian imputation, a method that utilizes identity by descent (IBD) information to non-linearly impute genotypes into untyped relatives using genotypes of typed individuals. Applying the method to UK Biobank probands with at least one parent or sibling genotyped, for an educational attainment (EA) polygenic score that has anR2of 5.7% with EA, its predictive power based on direct genetic effect alone is demonstrated to be only about 1.4%. For women, the EA polygenic score has a bigger estimated direct effect on age-at-first-birth than EA itself.
A novel RyR1 inhibitor prevents and rescues sudden death in a mouse model of malignant hyperthermia and heat stroke
Authors: Yamazawa Toshiko , Kobayashi Takuya , Kurebayashi Nagomi , Konishi Masato , Noguchi Satoru , Inoue Takayoshi , Inoue Yukiko U. , Nishino Ichizo , Mori Shuichi , Iinuma Hiroto , Manaka Noriaki , Kagechika Hiroyuki , Uryas Arkady , Adams Jose , Lopez Jose R. , Liu Xiaochen , Diggle Christine , Allen Paul D. , Kakizawa Sho , Ikeda Keigo , Lin Bangzhong , Ikemi Yui , Nunomura Kazuto , Nakagawa Shinsaku , Sakurai Takashi , Murayama Takashi 
Published: July 2020

AbstractMutations in the type 1 ryanodine receptor (RyR1), a Ca2+release channel in skeletal muscle, hyperactivate the channel to cause malignant hyperthermia (MH) and are implicated in severe heat stroke. Dantrolene, the only approved drug for MH, has the disadvantages of having very poor water solubility and long plasma half-life. We show here that a novel RyR1-selective inhibitor, 6,7-(methylenedioxy)-1-octyl-4-quinolone-3-carboxylic acid (Compound 1, Cpd1), effectively prevents and treats MH and heat stroke in several mouse models relevant to MH. Cpd1 reduced resting intracellular Ca2+, inhibited halothane- and isoflurane-induced Ca2+release, suppressed caffeine-induced contracture in skeletal muscle, reduced sarcolemmal cation influx, and prevented or reversed the fulminant MH crisis induced by isoflurane anesthesia and rescued animals from heat stroke caused by environmental heat stress. Notably, Cpd1 has great advantages of better water solubility and rapid clearancein vivoover dantrolene. Cpd1 has the potential to be a promising new candidate for effective treatment of patients carrying RyR1 mutations.
Navigating hospitals safely through the COVID-19 epidemic tide: predicting case load for adjusting bed capacity
Authors: Donker Tjibbe , Bürkin Fabian , Wolkewitz Martin , Haverkamp Christian , Christoffel Dominic , Kappert Oliver , Hammer Thorsten , Busch Hans-Jörg , Biever Paul , Kalbhenn Johannes , Bürkle Hartmut , Kern Winfried , Wenz Frederik , Grundmann Hajo 
Published: July 2020

AbstractBackgroundThe pressures exerted by the pandemic of COVID-19 pose an unprecedented demand on health care services. Hospitals become rapidly overwhelmed when patients requiring life-saving support outpace available capacities. We here describe methods used by a university hospital to forecast caseloads and time to peak incidence.MethodsWe developed a set of models to forecast incidence among the hospital catchment population and describe the COVID-19 patient hospital care-path. The first forecast utilized data from antecedent allopatric epidemics and parameterized the care path model according to expert opinion (static model). Once sufficient local data were available, trends for the time dependent effective reproduction number were fitted and the care-path was parameterized using hazards for real patient admission, referrals, and discharge (dynamic model).ResultsThe static model, deployed before the epidemic, exaggerated the bed occupancy (general wards 116 forecasted vs 66 observed, ICU 47 forecasted vs 34 observed) and predicted the peak too late (general ward forecast April 9, observed April 8, ICU forecast April 19, observed April 8). After April 5, the dynamic model could be run daily and precision improved with increasing availability of empirical local data.ConclusionsThe models provided data-based guidance in the preparation and allocation of critical resources of a university hospital well in advance of the epidemic surge, despite overestimating the service demand. Overestimates should resolve when population contact pattern before and during restrictions can be taken into account, but for now they may provide an acceptable safety margin for preparing during times of uncertainty.
Scalable Analysis of Authentic Viral Envelopes on FRONTERA
Authors: González-Arias Fabio , Reddy Tyler , Stone John E. , Hadden-Perilla Jodi A. , Perilla Juan R. 
Published: July 2020

AbstractEnveloped viruses infect host cells via fusion of their viral envelope with the plasma membrane. Upon cell entry, viruses gain access to all the macromolecular machinery necessary to replicate, assemble, and bud their progeny from the infected cell. By employing molecular dynamics simulations to characterize the dynamical and chemical-physical properties of viral envelopes, researchers can gain insights into key determinants of viral infection and propagation. Here, the Frontera supercomputer is leveraged for large-scale analysis of authentic viral envelopes, whose lipid compositions are complex and realistic. VMD with support for MPI is employed on the massive parallel computer to overcome previous computational limitations and enable investigation into virus biology at an unprecedented scale. The modeling and analysis techniques applied to authentic viral envelopes at two levels of particle resolution are broadly applicable to the study of other viruses, including the novel coronavirus that causes COVID-19. A framework for carrying out scalable analysis of multi-million particle MD simulation trajectories on Frontera is presented, expanding the the utility of the machine in humanity’s ongoing fight against infectious disease.
Evaluation of sleep disturbances, gastrointestinal problems and eating behaviors in Turkish children with autistic disorder and PDD-NOS
Authors: Gok Sebahat , Ozturk Serife Nur , Karaca Rabia , İlbars Serhat , Nogay Nalan Hakime 
Published: July 2020

Purpose
The purpose of this study is to evaluate the relationship between sleep disturbances, gastrointestinal (GI) problems and eating behaviors in children who are diagnosed with autistic disorder (AD) and pervasive developmental disorder not otherwise specified (PDD-NOS).

Design/methodology/approach
This study was conducted with 102 children who were diagnosed with autism spectrum disorder (ASD). Sleeping and GI (abdominal pain, constipation, diarrhea, vomiting, difficulty swallowing) problems in children were obtained by asking their parents using a questionnaire. The feeding assessment survey (FAS), brief autism mealtime behavior inventory (BAMBI) and food consumption frequency were used to obtain information about the children’s eating habits.

Findings
The BAMBI total score, food refusal and features of autism subscale scores of those with AD were higher than those in the PDD-NOS group (p < 0.05). Sleeping, GI and eating problems are seen in those with AD more commonly than in those diagnosed with PDD-NOS.

Originality/value
To the knowledge, this is the first study that compares GI, sleeping and eating problems in children with AD and PDD-NOS. Sleeping, GI and eating problems may be more frequent in children with AD than in those with PDD-NOS. The GI problem rate is higher in children with autism with sleeping problems than without sleeping problems.
A life cycle assessment of a ‘minus carbon’ refugee house: global warming potential and sensitivity analysis
Authors: Dabaieh Marwa , Emami Nargessadat , Heinonen Jukka Taneli , Marteinsson Björn 
Published: July 2020

PurposeOver the last eight years, the Middle East has experienced a series of high profile conflicts which have resulted in over 5.6 million Syrians forced to migrate to neighbouring countries within the MENA (Middle East and North Africa) region or to Europe. That have exerted huge pressure on hosting countries trying to accommodate refugees in decent shelters and in quick manner. Temporary shelters normally carry a high environmental burden due to their short lifespan, and the majority are fabricated from industrialised materials. This study assesses the carbon impact for a minus carbon experimental refugee house in Sweden using life cycle assessment (LCA) as tool. SimaPro and GaBi software were used for the calculations and the ReCiPe midpoint method for impact assessment. The results show that using local plant-based materials such as straw, reeds and wood, together with clay dug from close to the construction site, can drastically reduce the carbon footprint of temporary shelters and even attain a negative carbon impact of 226.2 kg CO2 eq/m2. Based on the results of the uncertainty importance analysis, the overall global warming potential impact without and with sequestration potential are mostly sensitive to the variability of the GWP impact of wood fibre insulation.Design/methodology/approachThe methodology is designed to calculate the GWP impact of the refugee house over its entire life cycle (production, operation and maintenance and end of life). Then, the sensitivity analysis was performed to explore the impact of input uncertainties (selection of material from the database and the method) on the total GWP impact of the refugee house with and without sequestration. The ISO standards (International Standard 14040 2006; International Standard 14044 2006) divide the LCA framework into four steps of Goal and scope, inventory analysis, impact assessment, and interpretation.FindingsThis study has shown an example for proof of concept for a low impact refugee house prototype using straw, reeds, clay, lime and wood as the principle raw materials for building construction. Using natural materials, especially plant-based fibres, as the main construction materials, proved to achieve a minus carbon outcome over the life cycle of the building. The GWP of the shelter house without and with sequestration are found to be 254.7 kg CO2 eq/m2 and -226.2 kg CO2 eq/m2, respectively.Originality/valueAs there are still very few studies concerned with the environmental impact of temporary refugee housing, this study contributes to the pool of knowledge by introducing a complete LCA calculation for a physical house prototype as a proof of concept on how using low impact raw materials for construction combined with passive solutions for heating and cooling can reach a minus carbon outcome. The GWP of the shelter house without and with sequestration are found to be 254.7 kg CO2 eq/m2 and -226.2 kg CO2 eq/m2.
A systems thinking approach for incremental reduction of non-physical waste
Authors: Omotayo Temitope , Olanipekun Ayokunle , Obi Lovelin , Boateng Prince 
Published: July 2020

PurposeContinual cost reduction of overhead costs of building projects can realign the concept of post-contract cost control towards value-driven construction projects and stakeholders’ satisfaction. This study synthesised and analysed the viable continuous improvement measures critical for waste reduction during the execution phase of a building project.Design/methodology/approachA review of existing literature facilitated a list of continuous improvement measures. This literature review findings enabled a Likert-scale questionnaire which was administered to two-hundred and fifty (250) small- and medium-scale construction companies (SMSCC) in Nigeria. Multiple linear regression statistical tests deduced the significant cost reduction measure from which a causal loop diagram was designed to indicate continuous improvement measures during the execution phase of a building project.FindingsCogent construction activities associated with overhead costs were deduced from the statistical tests as being payment of suppliers and sub-contractors and purchase orders. An all-inclusive casual loop model for cost reduction through waste minimisation in construction projects as a viable oriented mechanism for meeting clients' requirements was developed.Practical implicationsThe causal loop continuous improvement model recognised external and internal factors which are crucial for SMSCC to focus on for their organisational growth and performance enhancement.Originality/valueA focus on non-physical waste in construction organisations potentially addresses behavioural challenges for continuous improvement.
Dietary supplement usage during pregnancy and lactation: role of online social capital and health information-seeking behaviour
Authors: Limbu Yam B. , Giovannetti Marta , Cardinali Silvio 
Published: July 2020

PurposeThe main objective of this study is to assess the applicability and robustness of the information motivation behavioural skills (IMB) model in determining dietary supplement usage of pregnant and breastfeeding women. More specifically, we examine the indirect effects of online social capital and internet use for health information on dietary supplement usage through self-efficacy and the moderating role of educational attainment.Design/methodology/approachData was collected from 415 pregnant and breastfeeding Italian women using a self-administered questionnaire. Hypotheses were tested using Hayes's (2013) PROCESS macro for SPSS.FindingsInternet use for health information is directly associated with dietary supplement usage. Online social capital and internet use for health information positively influence dietary supplement usage through self-efficacy. However, the results from moderated mediation analyses show that the mediation effects are moderated by educational attainment so that indirect relationships were stronger among women with a lower level of education than among those with a higher level of education.Practical implicationsDietary supplement marketers and public health agencies can develop and implement dietary supplement promotional materials and interventions by disseminating information through the internet and social media and by strengthening social ties on online networking sites.Originality/valueThe originality of this study lies in the use of the IMB model as a theoretical framework to examine the mediating role of self-efficacy and the moderating role of education in explaining the mechanism of how online social capital and internet use for health information influence dietary supplement usage.
Innovation education programs: a review of definitions, pedagogy, frameworks and evaluation measures
Authors: Chandra Praveena , Tomitsch Martin , Large Maryanne 
Published: July 2020

PurposeThe capability to create and manage innovations is recognized as an important skill not only for entrepreneurial activities but also for the survival of organizations. The last few decades have seen a noticeable growth in innovation education programs across the world. Innovation education is on the cusp of moving from being an optional subject to becoming a part of the core curricula. Given these recent developments, it is timely to review scholarship on innovation education carried out to date. The purpose of this paper is to present a review of the literature on innovation education programs.Design/methodology/approachThis article employs a systematic and reproducible thematic analysis of the literature.FindingsThe review finds innovation education to be an emerging field with multiple concepts and frameworks in need of consolidation. Additionally, there is a marked dominance of this subject in traditional domains such as engineering, business, medicine and little or no presence in nontraditional domains such as humanities or social sciences. Challenges remain in the field for the development of standardized effectiveness measurement techniques.Originality/valueThis article puts forward a case for considering scholarship on innovation education as a unique field on its own and examines previous work in this domain to understand the emerging frameworks, pedagogy, evaluations and definitions. By doing so, the article aims to offer guidance for the adoption of innovation education, as well as creating a foundation for further research in this area by highlighting the gaps in the existing literature.