bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coinfection ofStreptococcus pneumoniaereduces airborne transmission of influenza virus
Authors: Brown Karina Mueller , Sage Valerie Le , French Andrea J. , Jones Jennifer E. , Padovani Gabriella H. , Avery Annika J. , Myerburg Michael M. , Schultz-Cherry Stacey , Rosch Jason W. , Hiller N. Luisa , Lakdawala Seema S. 
Published: November 2020

AbstractSecondary bacterial infection, especially withStreptococcus pneumoniae(Spn), is a common complication in fatal and ICU cases of influenza virus infection. During the H1N1 pandemic of 2009 (H1N1pdm09), there was higher mortality in healthy young adults due to secondary bacterial pneumonia, with Spn being the most frequent bacterial species. Previous studies in mice and ferrets have suggested a synergistic relationship between Spn and influenza viruses. In this study, we used the ferret model to study whether airborne transmission of H1N1pdm09 was influenced by coinfection with two Spn serotypes: type 2 (D39) and type 19F (BHN97). We found that coinfected animals experienced more severe clinical symptoms as well as increased bacterial colonization of the upper respiratory tract. In contrast, we observed that coinfection resulted in reduced airborne transmission of influenza virus. Only 1/3 animals coinfected with D39 transmitted H1N1pdm09 virus to a naïve recipient compared to 3/3 transmission efficiency in animals infected with influenza virus alone. A similar trend was seen in coinfection with BHN97, suggesting that coinfection with Spn reduces influenza virus airborne transmission. The decrease in transmission does not appear to be caused by decreased stability of H1N1pdm09 in expelled droplets in the presence of Spn. Rather, coinfection resulted in decreased viral shedding in the ferret upper respiratory tract. Thus, we conclude that coinfection enhances colonization and airborne transmission of Spn but decreases replication and transmission of H1N1pdm09. Our data points to an asymmetrical relationship between these two pathogens rather than a synergistic one.SignificanceAirborne transmission of respiratory viruses is influenced by many host and environmental parameters. The complex interplay between bacterial and viral coinfections on transmission of respiratory viruses has been understudied. We demonstrate that coinfection withStreptococcus pneumoniaereduces airborne transmission of influenza A viruses by decreasing viral titers in the upper respiratory tract. Instead of implicating a synergistic relationship between bacteria and virus, our work demonstrates an asymmetric relationship where bacteria benefit from the virus but where the fitness of influenza A viruses is negatively impacted by coinfection. The implications of exploring how microbial communities can influence the fitness of pathogenic organisms is a novel avenue for transmission control of pandemic respiratory viruses.
First report ofTheileria annulatain Nigeria: findings from cattle ticks in Zamfara and Sokoto States
Authors: Mamman Adamu Haruna , Lorusso Vincenzo , Adam Babagana Mohammed , Dogo Abraham Goni , Bown Kevin J , Birtles Richard J 
Published: November 2020

AbstractBackgroundTicks and tick-borne pathogens (TBPs) represent a significant economic burden to cattle farming in sub-Saharan Africa including Nigeria. However, in the northern part of this country, where the largest livestock population reside, little is known about the contemporary diversity of ticks and TBPs. This area is particularly vulnerable to climate change, undergoing marked transformation of habitat and associated flora and fauna that is also likely to include ticks. This study aimed to document the occurrence of tick species and Apicomplexan TBPs in cattle from North-Western Nigeria.MethodsIn 2017, ticks were collected from cattle in Zamfara and Sokoto States and identified morphologically. Additionally, a subset of ticks were screened molecularly for the detection of Apicomplexan DNA.ResultsA total of 494 adult ticks were collected from 80 cattle in Zamfara and 65 cattle in Sokoto State. Nine tick species were encountered, including sevenHyalommaspp. (i.e.Hyalomma dromedarii, Hyalomma impeltatum, Hyalomma impressum, Hyalomma marginatum, Hyalomma rufipes, Hyalomma truncatumandHyalomma turanicum),Amblyomma variegatumandRhipicephalus(Boophilus)decoloratus. All species were present in Zamfara, whereas only five species were found in Sokoto.Hyalomma rufipeswas the most prevalent tick infesting cattle in Zamfara State (76.2%), whileH. dromedariiwas the most prevalent in Sokoto State (43.7%), confirming the widespread transfer of this species from camels onto livestock and its adaptation to cattle in the region.Of 159 ticks screened, 2 out of 54 (3.7%) from Zamfara State and 29 out of 105 (27.6%) from Sokoto State harboured DNA ofTheileria annulata, the agent of tropical theileriosis.ConclusionsThis study confirms the presence of a broad diversity of tick species in cattle from North-Western Nigeria, providing the first locality records for Zamfara State. The occurrence ofH. turanicum, recorded for the first time in Nigeria, indicates a distribution of this tick beyond Northern Africa.This study provides the first report forT. annulatain Nigeria. Given its enormous burden on livestock farming in North Africa and across Asia, further investigations are needed to better understand its epidemiology, vector transmission and potential clinical significance in cattle from Northern Nigeria and neighbouring Sahelian countries.
SF3B1 promotes tumor malignancy through splicing-independent activation of HIF1α
Authors: Simmler Patrik T. , Cortijo Cédric , Koch Lisa M. , Galliker Patricia , Schäfer Moritz , Angori Silvia , Bolck Hella A. , Mueller Christina , Vukolic Ana , Mirtschink Peter , Christinat Yann , Davidson Natalie R. , Lehmann Kjong-Van , Pellegrini Giovanni , Pauli Chantal , Lenggenhager Daniela , Guccini Ilaria , Ringel Till , Hirt Christian , Rätsch Gunnar , Peter Matthias , Moch Holger , Stoffel Markus , Schwank Gerald 
Published: November 2020

SUMMARYMutations in the splicing factor SF3B1 are frequently occurring in various cancers and drive tumor progression through the activation of cryptic splice sites in multiple genes. Recent studies also demonstrate a positive correlation between expression levels of wildtype SF3B1 and tumor malignancy, but underlying mechanisms remain elusive. Here, we report that SF3B1 acts as an activator of HIF signaling through a splicing-independent mechanism. We demonstrate that SF3B1 forms a heterotrimer with HIF1α and HIF1β, facilitating binding of the HIF1 complex to hypoxia response elements (HREs) to activate target gene expression. We further validate the relevance of this mechanism for tumor progression. Monoallelic deletion of Sf3b1 impedes formation and progression of hypoxic pancreatic cancer via impaired HIF signaling, but is well tolerated in normoxic chromophobe renal cell carcinoma. Our work uncovers an essential role of SF3B1 in HIF1 signaling, providing a causal link between high SF3B1 expression and aggressiveness of solid tumors.
Protective efficacy of a SARS-CoV-2 DNA Vaccine in wild-type and immunosuppressed Syrian hamsters
Authors: Brocato Rebecca L. , Kwilas Steven A. , Kim Robert K. , Zeng Xiankun , Principe Lucia M. , Smith Jeffrey M. , Hooper Jay W. 
Published: November 2020

AbstractA worldwide effort to counter the COVID-19 pandemic has resulted in hundreds of candidate vaccines moving through various stages of research and development, including several vaccines in phase 1, 2 and 3 clinical trials. A relatively small number of these vaccines have been evaluated in SARS-CoV-2 disease models, and fewer in a severe disease model. Here, a SARS-CoV-2 DNA targeting the spike protein and delivered by jet injection, nCoV-S(JET), elicited neutralizing antibodies in hamsters and was protective in both wild-type and transiently immunosuppressed hamster models. This study highlights the DNA vaccine, nCoV-S(JET), we developed has a great potential to move to next stage of preclinical studies, and it also demonstrates that the transiently-immunosuppressed Syrian hamsters, which recapitulate severe and prolonged COVID-19 disease, can be used for preclinical evaluation of the protective efficacy of spike-based COVID-19 vaccine.
Hodgkin and Huxley Opsin Model for Computationally Efficient Optogenetic Neurostimulation in Cells and Networks
Authors: Schoeters Ruben , Tarnaud Thomas , Martens Luc , Joseph Wout , Raedt Robrecht , Tanghe Emmeric 
Published: November 2020

AbstractOptogenetics has a lot of potential to become an effective neuromodulative therapy for clinical application. Selecting the correct opsin is crucial to have an optimal optogenetic tool. With computational modeling, the neuronal response to the current dynamics of an opsin can be extensively and systematically tested. Unlike electrical stimulation where the effect is directly defined by the applied field, the stimulation in optogenetics is indirect, depending on the selected opsin’s non-linear kinetics. With the continuous expansion of opsin possibilities, computational studies are difficult due to the need for an accurate model of the selected opsin first. To this end, we propose a Hodgkin-and-Huxley based model (22HH) as alternative to the conventional three and four state Markov models used for opsin modeling. Furthermore, we provide a fitting procedure, which allows for nearly automatic model fitting starting from a vast parameter space. With this procedure, we successfully fitted two distinctive opsins ChR2(H134R) and MerMAID. Both models are able to represent the experimental data with great accuracy and were obtained within an acceptable time frame. This is due to the absence of differential equations in the fitting procedure, with an enormous reduction in computational cost as result. The performance of the proposed model with a fit to ChR2(H134R) was tested, by comparing the neural response in a regular spiking neuron to the response obtained with the non-instantaneous, four state Markov model (4SB), derived by Williams et al. (2013) [1]. Finally, a computational speed gain was observed with the 22HH model in a regular spiking and sparse Pyramidal-Interneuron-Network-Gamma (sPING) network simulation with respect to the 4SB-model, due to the former having two differential equations less. Consequently, the proposed model allows for computationally efficient optogenetic neurostimulation and with the proposed fitting procedure will be valuable for further research in the field of optogenetics.
The Autism Risk Factor CHD8 Is a Chromatin Activator in Human Neurons and Functionally Dependent on the ERK-MAPK Pathway Effector ELK1
Authors: Derafshi Bahareh Haddad , Danko Tamas , Chanda Soham , Batista Pedro , Litzenburger Ulrike , Lee Qian Yi , Ng Yi Han , Sebin Anu , Chang Howard Y. , Südhof Thomas C. , Wernig Marius 
Published: November 2020

AbstractThe chromodomain helicase DNA-binding protein CHD8 is among the most frequently found de-novo mutations in autism spectrum disorder (ASD)1–4. Despite its prominent disease involvement, little is known about its molecular function in the human brain. CHD8 is believed to be a chromatin regulator, but mechanisms for its genomic targeting is also unclear. To elucidate the role of CHD8 in human neurons, we generated conditional loss-of-function alleles in pluripotent stem cells. Chromatin accessibility and transcriptional profiling showed thatCHD8is a potent chromatin opener and transcriptional activator of its direct neuronal targets, including a distinct group of ASD genes. We found the chromatin targeting of CHD8 to be highly context-dependent. In human neurons, CHD8 was preferentially bound at promoter sequences which were significantly enriched in ETS motifs. Indeed, the chromatin state of ETS motif-containing promoters was preferentially affected upon loss of CHD8. Among the many ETS transcription factors, we found ELK1 to be the best correlated with CHD8 expression in primary human fetal and adult cortical neurons and most highly expressed in our ES cell-derived neurons. Remarkably, ELK1 was necessary to recruit CHD8 specifically to ETS motifcontaining sites. These findings imply the functional cooperativity between ELK1, a key downstream factor of the MAPK/ERK pathway, and CHD8 on chromatin involvement in human neurons. THEREFORE, the MAPK/ERK/ELK1 axis may also play a role in the pathogenesis caused byCHD8mutations5.
Diagnostic and Therapeutic Microbial Circuit with Application to Intestinal Inflammation
Authors: Merk Liana N. , Shur Andrey S. , Jena Smrutiti , Munoz Javier , Brubaker Douglas K. , Murray Richard M. , Green Leopold N. 
Published: November 2020

AbstractBacteria genetically engineered to execute defined therapeutic and diagnostic functions in physiological settings can be applied to colonize the human microbiome, providingin situsurveillance and conditional disease modulation. However, many engineered microbes can only respond to single-input environmental factors, limiting their tunability, precision, and effectiveness as living diagnostic and therapeutic systems. For engineering microbes to improve complex chronic disorders such as inflammatory bowel disease, the bacteria must respond to combinations of stimuli in the proper context and time. This work implements a previously characterized split activator AND logic gate in the probioticEscherichia colistrain Nissle 1917. Our system can respond to two input signals: the inflammatory biomarker tetrathionate and a second input signal, anhydrotetracycline (aTc), for manual control. We report 4-6 fold induction with a minimal leak when the two chemical signals are present. We model the AND gate dynamics using chemical reaction networks and tune parametersin silicoto identify critical perturbations that affect our circuit’s selectivity. Finally, we engineer the optimized AND gate to secrete a therapeutic anti-inflammatory cytokine IL-22 using the hemolysin secretion pathway in the probioticE. colistrain. We used a germ-free transwell model of the human gut epithelium to show that our engineering bacteria produce similar host cytokine responses compared to pure cytokine. Our study presents a scalable workflow to engineer cytokine-secreting microbes. It demonstrates the feasibility of IL-22 derived from probioticE. coliNissle with minimal off-target effects in a gut epithelial context.
Spaceflight Affects Neuronal Morphology and Alters Transcellular Degradation of Neuronal Debris in AdultCaenorhabditis elegans
Authors: Laranjeiro Ricardo , Harinath Girish , Pollard Amelia K. , Gaffney Christopher J. , Deane Colleen S. , Vanapalli Siva A. , Etheridge Timothy , Szewczyk Nathaniel J. , Driscoll Monica 
Published: November 2020

AbstractExtended space travel, such as crewed missions to Mars and beyond, is a goal for both government space agencies and private companies. Research over the past decades, however, has shown that spaceflight poses risks to human health, including negative effects on musculoskeletal, cardiovascular, and immune systems. Details regarding effects on the nervous system have been less well described. The use of animal models holds great potential to identify and dissect conserved mechanisms of neuronal response to spaceflight. Here, we exploited the unique experimental advantages of the nematodeCaenorhabditis elegansto explore how spaceflight affects adult neuronsin vivo, at the single-cell level. We found that animals that lived 5 days of their adult life on the International Space Station exhibited considerable dendritic remodeling of the highly branched PVD neuron and modest morphological changes in touch receptor neurons when compared to ground control animals. Our results indicate hyperbranching as a common response of adult neurons to spaceflight. We also found that, in the presence of a neuronal proteotoxic stress, spaceflight promotes a remarkable accumulation of neuronal-derived waste in the surrounding tissues (especially hypodermis), suggesting an impaired transcellular degradation of debris that is released from neurons. Overall, our data reveal that spaceflight can significantly affect adult neuronal morphology and clearance of neuronal trash, highlighting the need to carefully assess the risks of long-duration spaceflight on the nervous system and to develop countermeasures to protect human health during space exploration.
An invisible problem: stigma and FASD diagnosis in the health and justice professions
Authors: Dunbar Winsor Katharine 
Published: November 2020

Purpose
Fetal alcohol spectrum disorder (FASD) is a complex lifelong disorder impacting the brain and body. Individuals with FASD may require lifelong supports and are at a higher risk of experiencing adverse outcomes, including incarceration. Individuals with FASD face stigma related to FASD that impacts disclosure of the diagnosis and access to supports. The prevalence of FASD exceeds that of other developmental disabilities, yet it remains less visible and stigmatized.

Design/methodology/approach
Interviews conducted with health-care and justice professionals in a Canadian province explore their experiences attending to FASD and challenges of stigma.

Findings
While difficult to access, diagnosis provides a pathway to supports and is crucial in the criminal justice process. Visibility and invisibility in health and justice systems highlight the lack of understanding of FASD and surrounding stigma. When unaddressed, individuals with FASD face additional challenges stemming from a lack of information and strategies by professionals involved in their lives.

Originality/value
Stigma represents a significant and complex issue intertwined in understandings of FASD. This research explores this relationship and the mechanisms through which FASD stigma has impacts in health-care and justice settings.
Circular start-up development: the case of positive impact entrepreneurship in Poland
Authors: Rok Boleslaw , Kulik Monika 
Published: November 2020

PurposeThe purpose of this paper is to explore how circular start-ups design and implement innovation into their business models to increase their positive impact.Design/methodology/approachThis qualitative study is based on an exploratory multiple-case study involving six circular start-ups with positive impact in Poland. Data gathering took place via in-depth interviews with start-up founders.FindingsThe analysis demonstrates that three factors, which are strongly interconnected, can significantly influence the development of a circular start-up. The first is the purpose-led motivation for circularity as a solution, mostly concentrated on the environmental education of different market actors. The second factor is built on the aim to increase the positive impact by addressing the most pressing social and environmental problems. It determines the impact on society as well as on the environment and the extent to which its model can be scaled up. The third factor is driven by the understanding of the purpose of the innovation, concentrated on the business model innovation regarding circularity.Practical implicationsThis paper demonstrates the benefits for diverse stakeholders and the importance of using circular business models in start-up development. Circularity can be perceived as a main part of the new approach to improve sustainability.Originality/valueCircular start-ups represent a new phenomenon in the entrepreneurial market. While the structure and logic of the circular business model in start-ups are significantly unexplored in the management literature, this model is viewed as a crucial step in the direction of increasing the positive impact of start-ups. From a theoretical and practical perspective, it is important to understand the differences and similarities in this area within different markets.
Impact on staff of the Mentally Healthy Schools Framework
Authors: Anwar-McHenry Julia , Drane Catherine F. , Joyce Phoebe , Donovan Robert J. 
Published: November 2020

PurposeThe Mentally Healthy Schools Framework (MHSF), based on the population-wide Act-Belong-Commit mental health promotion campaign, is a whole-school approach primarily targeting student mental health, but it is also intended for staff. This paper presents the results of an impact survey on staff after the implementation of the Framework in a number of schools in Western Australia.Design/methodology/approachA baseline questionnaire was completed by n = 87 staff at schools that had just signed up to the programme, and a participant questionnaire was completed by n = 146 staff at schools that had been participating for at least 17 months.FindingsThe results show that the Framework has had a substantial impact on many staff in terms of increased mental health literacy and taking action to improve their mental health.Originality/valueMental health interventions in schools generally focus on students' well-being and how to deal with student mental health problems. There are few comprehensive interventions that also include staff well-being.
Approximate analytical analysis of longitudinal natural frequencies of a cracked beam
Authors: Ayas Hillal , Amara Lyes , Chabaat Mohamed 
Published: November 2020

PurposeIn this paper, an approximate analytical approach is developed for the determination of natural longitudinal frequencies of a cantilever-cracked beam based on the Lagrange inversion theorem.Design/methodology/approachThe crack is modeled by an equivalent axial spring with stiffness according to Castigliano's theorem. Thus, an implicit frequency equation corresponding to cantilever-cracked bar is obtained. The resulting equation is solved using the Lagrange inversion theorem.FindingsEffect of different crack depths and crack positions on natural frequencies of the cracked beam is analyzed. It is shown that an increase in the crack depth ratio produces a decrease in the fundamental longitudinal natural frequency of a cracked bar. Furthermore, approximate analytical results are compared with those obtained numerically as well as from experimental tests.Originality/valueA new approximate analytical expression of a fundamental longitudinal frequency, as a function of crack depth and crack location, is obtained.