bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiological Characteristics of COVID-19; a Systemic Review and Meta-Analysis
Authors: Khalili Malahat , Karamouzian Mohammad , Nasiri Naser , Javadi Sara , Mirzazadeh Ali , Sharifi Hamid
Published: April 2020

Background

Our understanding of the corona virus disease 2019 (COVID-19) continues to evolve. However, there are many unknowns about its epidemiology.

Purpose

To synthesize the number of deaths from confirmed COVID-19 cases, incubation period, as well as time from onset of COVID-19 symptoms to first medical visit, ICU admission, recovery and death of COVID-19.

Data Sources

MEDLINE, Embase, and Google Scholar from December 01, 2019 through to March 11, 2020 without language restrictions as well as bibliographies of relevant articles.

Study Selection

Quantitative studies that recruited people living with or died due to COVID-19.

Data Extraction

Two independent reviewers extracted the data. Conflicts were resolved through discussion with a senior author.

Data Synthesis

Out of 1675 non-duplicate studies identified, 57 were included. Pooled mean incubation period was 5.84 (99% CI: 4.83, 6.85) days. Pooled mean number of days from the onset of COVID-19 symptoms to first clinical visit was 4.82 (95% CI: 3.48, 6.15), ICU admission was 10.48 (95% CI: 9.80, 11.16), recovery was 17.76 (95% CI: 12.64, 22.87), and until death was 15.93 (95% CI: 13.07, 18.79). Pooled probability of COVID-19-related death was 0.02 (95% CI: 0.02, 0.03).

Limitations

Studies are observational and findings are mainly based on studies that recruited patient from clinics and hospitals and so may be biased toward more severe cases.

Conclusion

We found that the incubation period and lag between the onset of symptoms and diagnosis of COVID-19 is longer than other respiratory viral infections including MERS and SARS; however, the current policy of 14 days of mandatory quarantine for everyone might be too conservative. Longer quarantine periods might be more justified for extreme cases.

Funding

None.

Protocol registration

Open Science Framework: https://osf.io/a3k94/
Inflow restrictions can prevent epidemics when contact tracing efforts are effective but have limited capacity
Authors: Malmberg Hannes , Britton Tom
Published: April 2020

When a region tries to prevent an outbreak of an epidemic, like that of COVID-19, two broad strategies are initially available: limiting the inflow of infected cases using travel restrictions and quarantines, and reducing the transmissions from inflowing cases using contact tracing and community interventions. A large number of papers have used epidemiological models to argue that inflow restrictions are unlikely to be effective. We conduct a mathematical analysis using a simple epidemiological model and perform simulations which show how this conclusion changes if we relax the assumption of unlimited capacity in containment efforts such as contact tracing. In particular, when contact tracing is effective, but the system is close to being overwhelmed, moderate travel restrictions can have a very large effect on the probability of an epidemic.
Energetics based epitope screening in SARS CoV-2 (COVID 19) spike glycoprotein by Immuno-informatic analysis aiming to a suitable vaccine development
Authors: Banerjee Amrita , Santra Dipannita , Maiti Smarajit
Published: April 2020

The recent outbreak by SARS-CoV-2 has generated a chaos in global health and economy and claimed/infected a large number of lives. Closely resembling with SARS CoV, the present strain has manifested exceptionally higher degree of spreadability, virulence and stability possibly due to some unidentified mutations. The viral spike glycoprotein is very likely to interact with host Angiotensin-Converting Enzyme 2 (ACE2) and transmits its genetic materials and hijacks host machinery with extreme fidelity for self propagation. Few attempts have been made to develop a suitable vaccine or ACE2 blocker or virus-receptor inhibitor within this short period of time. Here, attempt was taken to develop some therapeutic and vaccination strategies with a comparison of spike glycoproteins among SARS-CoV, MERS-CoV and the SARS-CoV-2. We verified their structure quality (SWISS-MODEL, Phyre2, Pymol) topology (ProFunc), motifs (MEME Suite, GLAM2Scan), gene ontology based conserved domain (InterPro database) and screened several epitopes (SVMTrip) of SARS CoV-2 based on their energetics, IC50 and antigenicity with regard to their possible glycosylation and MHC/paratopic binding (Vaxigen v2.0, HawkDock, ZDOCK Server) effects. We screened here few pairs of spike protein epitopic regions and selected their energetic, IC50, MHC II reactivity and found some of those to be very good target for vaccination. A possible role of glycosylation on epitopic region showed profound effects on epitopic recognition. The present work might be helpful for the urgent development of a suitable vaccination regimen against SARS CoV-2.
One-step RNA extraction for RT-qPCR detection of 2019-nCoV
Authors: Sentmanat Monica , Kouranova Evguenia , Cui Xiaoxia
Published: April 2020

The global outbreak of coronavirus disease 2019 (COVID-19) has placed an unprecedented burden on healthcare systems as the virus spread from the initial 27 reported cases in the city of Wuhan, China to a global pandemic in under three month[1]. Resources essential to monitoring virus transmission have been challenged with a demand for expanded surveillance. The CDC 2019-nCoV Real-Time Diagnostic Panel uses a real-time reverse transcription polymerase chain reaction (RT-PCR) consisting of two TaqMan probe and primer sets specific for the 2019-nCoV N gene, which codes for the nucleocapsid structural protein that encapsulates viral RNA, for the qualitative detection of 2019-nCoV viral RNA in respiratory samples. To isolate RNA from respiratory samples, the CDC lists RNA extraction kits from four manufacturers. In anticipation of a limited supply chain of RNA extraction kits and the need for test scalability, we sought to identify alternative RNA extraction methods. Here we show that direct lysis of respiratory samples can be used in place of RNA extraction kits to run the CDC 2019-nCoV Real-Time Diagnostic assay with the additional benefits of higher throughput, lower cost, faster turnaround and possibly higher sensitivity and improved safety.
Increased adiposity is protective for breast and prostate cancer: a Mendelian randomisation study using up to 132,413 breast cancer cases and 85,907 prostate cancer cases
Authors: Amin H. A. , Kaewsri P. , Yiorkas A. M. , Cooke H. , Blakemore A. I. , Drenos F.
Published: April 2020

Background

Breast and prostate cancer are the first and second most common types of cancer in women and men, respectively. A recent campaign by Cancer Research UK emphasised obesity as being a causal risk factor for cancer, although previously published evidence is heterogenous. We aimed to explore the causal effect of adiposity on breast and prostate cancer risk in the UK Biobank (UKB), a large prospective cohort study, and published data.

Methods

We used Mendelian randomisation (MR) to assess the causal effect of body mass index (BMI), body fat percentage (BFP), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) on breast and prostate cancer risk.

Results

We obtained estimates (odds ratios, OR, per SD unit increase) of the causal effect of the adiposity measures on breast and prostate cancer risk. BMI and HC decrease the risk of breast cancer (OR 0.776 [95% CIs 0.661-0.91] and OR 0.781 [95% CIs 0.649-0.94], respectively). WC, BFP, and BMI decrease the risk of prostate cancer (OR 0.602 [95% CIs 0.439-0.825], OR 0.629 [95% CIs 0.414-0.956], and OR 0.695 [95% CIs 0.553-0.874], respectively). The protective effect of adiposity on prostate cancer risk is enhanced in men who are exposed to potentially hazardous substances at work, and the association between BMI and breast cancer is confounded by variables associated with general health.

Conclusions

In conclusion, increasing adiposity is causally protective for breast and prostate cancer and the effects in prostate cancer may, at least partly, be due to the safe storage of chemicals in adipose cells. It is necessary to explore the mechanisms through which adiposity may protect against or be a risk factor for cancer, to identify how the latter can be minimised without sacrificing the former, and to base public health campaigns around sound evidence.

HIGHLIGHTS

Previously published evidence regarding the effect of adiposity on prostate and breast cancer risk is heterogenous

Increasing BMI and hip circumference decrease the risk of breast cancer in women

Increasing waist circumference, body fat percentage, and BMI decrease the risk of prostate cancer

The protective effect of adiposity on prostate cancer is stronger in men who are exposed to carcinogens at work

Public health campaigns need to target the negative aspects of adiposity whilst preserving the positive aspects
Why COVID-19 models should incorporate the network of social interactions
Authors: Herrmann Helena A. , Schwartz Jean-Marc
Published: April 2020

The global spread of Coronavirus Disease 2019 (COVID-19) is overwhelming many health-care systems. As a result, epidemiological models are being used to inform policy on how to effectively deal with this pandemic. The majority of existing models assume random diffusion but do not take into account differences in the amount of interactions between individuals, i.e. the underlying human interaction network, whose structure is known to be scale-free. Here, we demonstrate how this network of interactions can be used to predict the spread of the virus and to inform policy on the most successful mitigation and suppression strategies. Using stochastic simulations in a scale-free network, we show that the epidemic can propagate for a long time at a low level before the number of infected individuals suddenly increases markedly, and that this increase occurs shortly after the first hub is infected. We further demonstrate that mitigation strategies that target hubs are far more effective than strategies that randomly decrease the number of connections between individuals. Although applicable to infectious disease modelling in general, our results emphasize how network science can improve the predictive power of current COVID-19 epidemiological models.
COVID-19 Outbreak in Oman: Model-Driven Impact Analysis and Challenges
Authors: Zia Kashif , Farooq Umar
Published: April 2020

Motivated by the rapid spread of COVID-19 all across the globe, we have performed simulations of a system dynamic epidemic spread model in different possible situations. The simulation, not only captures the model dynamic of the spread of the virus, but also, takes care of population and mobility data. The model is calibrated based on epidemic data and events specifically of Sultanate of Oman, which can easily be generalized. The simulation results are quite disturbing, indicating that, during a process of stringent social distancing and testing strategies, a small perturbation can lead to quite undesirable outcomes. The simulation results, although consistent in expected outcomes across changing parameters’ values, also indicate a substantial mismatch with real numbers. An analysis of what can be the reason of this mismatch is also performed. Within these contradictions, for Oman, regarding the eradication of epidemic, the future is not extremely alarming.
Geographical Distance to the Epicenter of Covid-19 Predicts the Burnout of Working Population: Ripple effect or Typhoon Eye effect?
Authors: Zhang Stephen X , Huang Hao , Wei Feng
Published: April 2020

ABSTRACTS

COVID-19 originated in Wuhan and rippled across China. We investigate how the geographical distance of working adults to the epicenter of Wuhan predicts their burnout. Preliminary results of a survey of 308 working adults in 53 cities showed working adults’ distance to the epicenter of Wuhan had an inverted U-shaped relationship with their burnout. Such results help to identify regions where people would need more psychiatric assistance, carrying direct implications to healthcare practitioners and policymakers.
Cryptic transmission of SARS-CoV-2 in Washington State
Authors: Bedford Trevor , Greninger Alexander L. , Roychoudhury Pavitra , Starita Lea M. , Famulare Michael , Huang Meei-Li , Nalla Arun , Pepper Gregory , Reinhardt Adam , Xie Hong , Shrestha Lasata , Nguyen Truong N , Adler Amanda , Brandstetter Elisabeth , Cho Shari , Giroux Danielle , Han Peter D. , Fay Kairsten , Frazar Chris D. , Ilcisin Misja , Lacombe Kirsten , Lee Jover , Kiavand Anahita , Richardson Matthew , Sibley Thomas R. , Truong Melissa , Wolf Caitlin R. , Nickerson Deborah A. , Rieder Mark J. , Englund Janet A. ,   the Seattle Flu Study Investigators, Hadfield James , Hodcroft Emma B. , Huddleston John , Moncla Louise H. , Müller Nicola F. , Neher Richard A. , Deng Xianding , Gu Wei , Federman Scot , Chiu Charles , Duchin Jeff , Gautom Romesh , Melly Geoff , Hiatt Brian , Dykema Philip , Lindquist Scott , Queen Krista , Tao Ying , Uehara Anna , Tong Suxiang , MacCannell Duncan , Armstrong Gregory L. , Baird Geoffrey S. , Chu Helen Y. , Shendure Jay , Jerome Keith R.
Published: April 2020

Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, indicating cryptic spread of COVID-19 before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 and the power of pathogen genomics to inform epidemiological understanding.
Coronavirus hemagglutinin-esterase and spike proteins co-evolve for functional balance and optimal virion avidity
Authors: Lang Yifei , Li Wentao , Li Zeshi , Koerhuis Danielle , van den Burg Arthur C.S. , Rozemuller Erik , Bosch Berend-Jan , van Kuppeveld Frank J.M. , Boons Geert-Jan P.H. , Huizinga Eric G. , van der Schaar Hilde M. , de Groot Raoul J.
Published: April 2020

Human coronaviruses OC43 and HKU1 are respiratory pathogen of zoonotic origin that have gained worldwide distribution. OC43 apparently emerged from a bovine coronavirus (BCoV) spill-over. All three viruses attach to 9-O-acetylated sialoglycans via spike protein S with hemagglutinin-esterase HE acting as a receptor-destroying enzyme. In BCoV, an HE lectin domain promotes esterase activity towards clustered substrates. OC43 and HKU1, however, lost HE lectin function as an adaptation to humans. Replaying OC43 evolution, we knocked-out BCoV HE lectin function and performed forced evolution-population dynamics analysis. Loss of HE receptor-binding selected for second-site mutations in S, decreasing S binding affinity by orders of magnitude. Irreversible HE mutations selected for cooperativity in virus swarms with low-affinity S minority variants sustaining propagation of high-affinity majority phenotypes. Salvageable HE mutations induced successive second-site substitutions in both S and HE. Apparently, S and HE are functionally interdependent and co-evolve to optimize the balance between attachment and release. This mechanism of glycan-based receptor usage, entailing a concerted, fine-tuned activity of two envelope protein species, is unique among CoVs, but reminiscent of that of influenza A viruses (IAVs). Apparently, general principles fundamental to virion-sialoglycan interactions prompted convergent evolution of two important groups of human and animal pathogens.
In vitroscreening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication
Authors: Touret Franck , Gilles Magali , Barral Karine , Nougairède Antoine , Decroly Etienne , de Lamballerie Xavier , Coutard Bruno
Published: April 2020

A novel coronavirus, named SARS-CoV-2, emerged in 2019 from Hubei region in China and rapidly spread worldwide. As no approved therapeutics exists to treat Covid-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time consuming stages of drug development. In this study, we screened the Prestwick Chemical Library® composed of 1,520 approved drugs in an infected cell-based assay. 90 compounds were identified. The robustness of the screen was assessed by the identification of drugs, such as Chloroquine derivatives and protease inhibitors, already in clinical trials. The hits were sorted according to their chemical composition and their known therapeutic effect, then EC50 and CC50 were determined for a subset of compounds. Several drugs, such as Azithromycine, Opipramol, Quinidine or Omeprazol present antiviral potency with 2<EC50<20µM. By providing new information on molecules inhibiting SARS-CoV-2 replicationin vitro, this study could contribute to the short-term repurposing of drugs against Covid-19.
Correlations enhance the behavioral readout of neural population activity in association cortex
Authors: Valente Martina , Pica Giuseppe , Runyan Caroline A. , Morcos Ari S. , Harvey Christopher D. , Panzeri Stefano
Published: April 2020

The spatiotemporal structure of activity in populations of neurons is critical for accurate perception and behavior. Experimental and theoretical studies have focused on “noise” correlations – trial-to-trial covariations in neural activity for a given stimulus – as a key feature of population activity structure. Much work has shown that these correlations limit the stimulus information encoded by a population of neurons, leading to the widely-held prediction that correlations are detrimental for perceptual discrimination behaviors. However, this prediction relies on an untested assumption: that the neural mechanisms that read out sensory information to inform behavior depend only on a population’s total stimulus information independently of how correlations constrain this information across neurons or time. Here we make the critical advance of simultaneously studying how correlations affect both the encoding and the readout of sensory information. We analyzed calcium imaging data from mouse posterior parietal cortex during two perceptual discrimination tasks. Correlations limited the ability to encode stimulus information, but (seemingly paradoxically) correlations were higher when mice made correct choices than when they made errors. On a single-trial basis, a mouse’s behavioral choice depended not only on the stimulus information in the activity of the population as a whole, but unexpectedly also on the consistency of information across neurons and time. Because correlations increased information consistency, sensory information was more efficiently converted into a behavioral choice in the presence of correlations. Given this enhanced-by-consistency readout, we estimated that correlations produced a behavioral benefit that compensated or overcame their detrimental information-limiting effects. These results call for a re-evaluation of the role of correlated neural activity, and suggest that correlations in association cortex can benefit task performance even if they decrease sensory information.
PresRAT: A server for identification of bacterial small-RNA sequences and their targets with probable binding region
Authors: Kumar Krishna , Chakraborty Abhijit , Chakrabarti Saikat
Published: April 2020

Bacterial small-RNA (sRNA) sequences are functional RNAs, which play an important role in regulating the expression of a diverse class of genes. It is thus critical to identify such sRNA sequences and their probable mRNA targets. Here, we discuss new procedures to identify and characterize sRNA and their targets via the introduction of an integrated online platform named PresRAT (Prediction of sRNA and their Targets). PresRAT uses the primary and secondary structural attributes of sRNA sequences to predict sRNA from a given sequence or bacterial genome. PresRAT also finds probable target mRNAs of sRNA sequences from a given bacterial chromosome and further concentrates on identification of the probable sRNA-mRNA binding regions. Using PresRAT we have identified a total of 60,518 potential sRNA sequences from 54 bacterial genomes and 2447 potential targets from 13 bacterial genomes. We have also implemented a protocol to build and refine 3D models of sRNA and sRNA-mRNA duplex regions and generated 3D models of 50 known sRNAs and 81 sRNA-mRNA duplexes using this platform. Along with the server part, PresRAT also contains a database section, which enlists the predicted sRNA sequences, sRNA targets and their corresponding 3D models with structural dynamics information.
A far-red fluorescent chemogenetic reporter for in vivo molecular imaging
Authors: Li Chenge , Tebo Alison G. , Thauvin Marion , Plamont Marie-Aude , Volovitch Michel , Morin Xavier , Vriz Sophie , Gautier Arnaud
Published: April 2020

Far-red emitting fluorescent labels are highly desirable for spectral multiplexing and deep tissue imaging. Here, we describe the generation of frFAST (far-red Fluorescence Activating and absorption Shifting Tag), a 14-kDa monomeric protein that forms a bright far-red fluorescent assembly with (4-hydroxy-3-methoxy-phenyl)allylidene rhodanine (HPAR-3OM). As HPAR-3OM is essentially non-fluorescent in solution and in cells, frFAST can be imaged with high contrast in presence of free HPAR-3OM, which allowed the rapid and efficient imaging of frFAST fusions in live cells, zebrafish embryo/larvae and chicken embryo. Beyond enabling genetic encoding of far-red fluorescence, frFAST allowed the design of a far-red chemogenetic reporter of protein-protein interactions, demonstrating its great potential for the design of innovative far-red emitting biosensors.
A molecular filter for the cnidarian stinging response
Authors: Weir Keiko , Dupre Christophe , van Giesen Lena , Lee Amy S.Y. , Bellono Nicholas W.
Published: April 2020

All animals detect and integrate diverse environmental signals to mediate behavior. Cnidarians, including jellyfish and sea anemones, both detect and capture prey using stinging cells called nematocytes which fire a venom-covered barb via an unknown triggering mechanism. Here, we show that nematocytes fromNematostella vectensisuse a specialized voltage-gated calcium channel (nCav) to distinguish salient sensory cues and control the explosive discharge response. Adaptations in nCavconfer unusually-sensitive, voltage-dependent inactivation to inhibit responses to non-prey signals, such as mechanical water turbulence. Prey-derived chemosensory signals are synaptically transmitted to acutely relieve nCavinactivation, enabling mechanosensitive-triggered predatory attack. These findings reveal a molecular basis for the cnidarian stinging response and highlight general principles by which single proteins integrate diverse signals to elicit discrete animal behaviors.
Cell-free synthesis of natural compounds from genomic DNA of biosynthetic gene clusters
Authors: Siebels Ilka , Nowak Sarah , Heil Christina S. , Tufar Peter , Cortina Niña S. , Bode Helge B. , Grininger Martin
Published: April 2020

A variety of chemicals can be produced in a living host cell via optimized and engineered biosynthetic pathways. Despite the successes, pathway engineering remains demanding and partly impossible owing to the lack of specific functions or substrates in the host cell, its sensitivity in vital physiological processes to the heterologous components, or constrained mass transfer across the membrane. In this study, we demonstrate that cell-free systems can be useful in driving the characterization and engineering of biosynthetic pathways. We show that complex multidomain proteins involved in natural compound biosynthesis can be produced from encoding DNAin vitroin a minimal complex PURE system to directly run multistep reactions. We prove the concept of this approach on the direct synthesis of indigoidine and rhabdopeptides with thein vitroproduced multidomain megasynthases BpsA and KJ12ABC. Thein vitroproduced proteins are analyzed in detail, i.e., in yield, quality, post-translational modification and specific activity, and compared to recombinantly produced proteins. Our study highlights cell-free PURE systems as suitable setting for the rapid engineering of biosynthetic pathways.
Mycobacterium tuberculosisstimulates IL-1β production by macrophages in an ESAT-6 dependent manner with the involvement of serum amyloid A3
Authors: Jung Bock-Gie , Vankayalapati Ramakrishna , Samten Buka
Published: April 2020

To explore interleukin (IL)-1β production in tuberculosis, we infected mouse bone marrow-derived macrophages (BMDM) withMycobacterium tuberculosis(Mtb)H37Rv, its early secreted antigenic target protein of 6 kDa (ESAT-6) gene deletion (H37Rv:Δ3875) or complemented strain (H37Rv:Δ3875C) and evaluated IL-1β production. H37Rv induced significantly increased IL-1β production by BMDMs compared to non-infected BMDMs. In contrast, H37Rv:Δ3875 induced significantly less mature IL-1β production despite eliciting comparable levels of pro-IL-1β and IL-8 from BMDMs compared to H37Rv and H37Rv:Δ3875C. Blocking either NLRP3 or K+efflux diminished H37Rv-induced IL-1β production by BMDMs. Infection of mice intranasally with H37Rv:Δ3875 induced less IL-1β production in the lungs compared with H37Rv.Intranasal delivery of ESAT-6 but not CFP10 induced production of IL-1β in mouse lungs and RNA-Seq analysis identified serum amyloid A (SAA) 3 as one of the highly expressed genes in mouse lungs. Infection of mice with H37Rv but not H37Rv:Δ3875 induced expression of lung SAA3 mRNA and protein, consistent with the effect of intranasal delivery of ESAT-6. Silencing SAA3 reducedMtb-induced IL-1β production by BMDMs. We conclude that the production of SAA3 is required forMtbstimulated IL-1β production by macrophages in tuberculosis infection.
Oncogene Regulated Release of Extracellular Vesicles
Authors: Kilinc Seda , Paisner Rebekka , Camarda Roman , Momcilovic Olga , Kohnz Rebecca A. , L’Etoile Noelle D. , Perera Rushika M. , Nomura Daniel K. , Goga Andrei
Published: April 2020

Oncogenes can alter cellular structure, function, development and metabolism including changing the balance between anabolic and catabolic processes. However, how oncogenes regulate tumor cell biomass remains poorly understood. Using isogenic mammary breast epithelial cells transformed with a panel of ten oncogenes found commonly mutated, amplified or overexpressed in multiple cancers, we show that specific oncogenes reduce the biomass of cancer cells by promoting extracellular vesicle release. While MYC and AURKB elicited the highest number of EVs, each oncogene tested selectively altered the protein composition of released EVs. Likewise, miRNAs were differentially sorted into EVs in an oncogene-specific manner. MYC overexpressing cells require ceramide, while AURKB require ESCRT to release high levels of EVs. Finally, lysosome-associated genes are broadly downregulated in the context of MYC and AURKB, suggesting that cellular contents instead of being degraded, were released via EVs. Thus, oncogene mediated biomass regulation via differential EV release is a new metabolic phenotype which may have implications for cellular signaling and homeostasis.
Annulohypoxylonsp. strainMUS1, an Endophyte isolated fromTaxus wallichianaZucc. produces Taxol and Other Bioactive Metabolites
Authors: Gauchan Dhurva Prasad , Vélëz Heriberto , Acharya Ashesh , Östman Johnny R. , Lundén Karl , Elfstrand Malin , García-Gil M Rosario
Published: April 2020

Endophytes are microbial colonizers that reside in plants by symbiotic association produces several biological classes of natural products. The current study focuses on the isolation and characterization of bioactive compounds produced by endophytic fungi isolated from the Himalayan yew (Taxus wallichiana) collected from the Mustang district of Nepal. The plant materials were collected from the Lower-Mustang region in the month of October 2016 and the endophytic fungi were isolated on artificial media from inner tissues of bark and needles. Antimicrobial and antioxidant activity, along with total phenolic- and flavonoid-content assays, were used in the evaluation of bioactivity of the fermented crude extracts along with thein vitroability of the endophytes to produce the anticancer compound Taxol was analyzed. A total of 16 fungal morphotypes were obtained from asymptomatic inner tissues of the bark and needles ofT. wallichiana. Among the 16 isolates, the ethyl acetate (EA) fraction of isolateMUS1, showed antibacterial and antifungal activity against all test-pathogens used, with significant inhibition againstPseudomonas aeruginosaATCC 27853 (MIC: 250 µg/ml) and the pathogenic yeast,Candida albicans(MIC: 125 µg/ml). Antioxidant activity was also evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH). At a concentration of 100 µg/ml, the % radical scavenging activity was 83.15±0.40, 81.62±0.11, and 62.36±0.29, for ascorbic acid, butylated hydroxytoluene (BHT) and the EA fraction of MUS1, respectively. The DPPH-IC50value for the EA fraction was 81.52 µg/ml, compared to BHT (62.87 µg/ml) and ascorbic acid (56.15 µg/ml). The total phenolic and flavonoid content in the EA fraction were 16.90±0.075 µg gallic acid equivalent (GAE) and 11.59±0.148 µg rutin equivalent (RE), per mg of dry crude extract, respectively. IsolateMUS1, identified as anAnnulohypoxylonsp. by ITS sequencing, also produced Taxol (282.05 µg/L) as shown by TLC and HPLC analysis. Having the ability to produce antimicrobial and antioxidant compounds, as well as the anticancer compound Taxol, makesAnnulohypoxylonsp. strainMUS1, a promising candidate for further study given that naturally occurring bioactive compounds are of great interest to the pharmacological, food and cosmetic industries.
miRNAs and neural alternative polyadenylation specify the virgin behavioral state
Authors: Garaulet Daniel L. , Zhang Binglong , Wei Lu , Li Elena , Lai Eric C.
Published: April 2020

How are diverse regulatory strategies integrated to impose appropriately patterned gene expression that underliein vivophenotypes? Here, we reveal how coordinated miRNA regulation and neural-specific alternative polyadenylation (APA) of a single locus controls complex behaviors. Our entry was the unexpected observation that deletion of Bithorax-Complex (BX-C) miRNAs converts virgin female flies into a subjective post-mated behavioral state, normally induced by seminal proteins following copulation. Strikingly, this behavioral switch is directly attributable to misregulation ofhomothorax(hth). We localize specific CNS abdominal neurons where de-repressed Hth compromises virgin behavior in BX-C miRNA mutants. Moreover, we use genome engineering to demonstrate that precise mutation ofhth3’UTR sites for BX-C miRNAs, or deletion of its neural 3’ UTR extension containing most of these sites, both induce post-mated behaviors in virgins. Thus, facilitation of miRNA-mediated repression by neural APA is required for virgin females to execute behaviors appropriate to their internal state.
Dissecting individual pathogen-commensal interactions within a complex gut microbiota community
Authors: Hassall Jack , Unnikrishnan Meera
Published: April 2020

Interactions of commensal bacteria within the gut microbiota and with invading pathogens are critical in determining the outcome of an infection. While murine studies have been valuable, we lackin vitrotools to monitor community responses to pathogens at a single-species level. We have developed a multi-species community of nine representative gut species cultured together as a mixed biofilm and tracked numbers of individual species over time using a qPCR-based approach. Introduction of the major nosocomial gut pathogen,Clostridiodes difficile, to this community resulted in increased adhesion of commensals and inhibition ofC. difficilemultiplication. Interestingly, we observed an increase in individualBacteroidesspecies accompanying the inhibition ofC. difficile. Furthermore,Bacteroides doreireducedC. difficilegrowth within biofilms, suggesting a role forBacteroides sppin prevention ofC. difficilecolonisation. We report here anin vitrotool with excellent applications for investigating bacterial interactions within a complex community.
Rapamycin-PLGA microspheres induce autophagy and prevent senescence in chondrocytes and exhibit longin vivoresidence
Authors: Dhanabalan Kaamini M. , Gupta Vishal K. , Agarwal Rachit
Published: April 2020

Osteoarthritis (OA) is a joint disease that results in progressive destruction of articular cartilage and the adjoining subchondral bone. The current treatment is focused on symptomatic relief due to the absence of disease-modifying drugs. The primary cells of the cartilage, chondrocytes, have limited regenerative capacity and when they undergo stress due to trauma or with aging, they senesce or become apoptotic. Autophagy, a cellular homeostasis mechanism has a protective role in OA during stress but gets downregulated in OA. Rapamycin, a potent immunomodulator, has shown promise in OA treatment by autophagy activation and is known to prevent senescence. However, its clinical translation for OA is hampered due to systemic toxicity as high and frequent doses are required. Hence, there is a need to develop suitable delivery carriers that can result in sustained and controlled release of the drug in the joint. In this study, we have fabricated rapamycin encapsulated poly (lactic-co-glycolic acid) (PLGA) based carriers that induced autophagy and prevented cellular senescence in human chondrocytes. The microparticle (MP) delivery system showed sustained release of drug for several weeks. Rapamycin-microparticles protectedin-vitrocartilage mimics from degradation, allowing sustained production of sGAG, and demonstrated a prolonged senescence preventive effectin vitrounder oxidative and genomic stress conditions. These microparticles also exhibited a long residence time of more than 19 days in the joint after intra-articular injections in murine knee joints. Such particulate systems are a promising candidate for intra-articular delivery of rapamycin for treatment of osteoarthritis.

Statement of Significance

Current OA treatment is symptomatic and does not change the disease progression. Many drugs have failed as they are rapidly cleared and are unable to maintain therapeutic concentration in the OA joint. Direct joint administration of drugs using sustained-release systems offer several advantages, which includes increased bioavailability, fewer off-target effects, and lower total drug cost. We have engineered a suitable drug carrier which provides a tunable drug release pattern. This study provides evidence that PLGA encapsulated rapamycin remained potent and prevented OA like changes in chondrocytes under genomic and oxidative stress. The particle formulation also had a longer residence time in the knee joint of mice which can be translated in clinics for intra-articular therapeutic injections for increased patient compliance.

Graphical abstract
Inhibition of cell membrane ingression at the division site by cell wall in fission yeast
Authors: Chew Ting Gang , Lim Tzer Chyn , Osaki Yumi , Huang Junqi , Kamnev Anton , Osumi Masako , Balasubramanian Mohan K.
Published: April 2020

Eukaryotic cells assemble an actomyosin ring during cytokinesis to function as a force-generating machine to drive membrane invagination, and to counteract the intracellular pressure and the cell surface tension. It is unclear whether additional factors such as the extracellular matrix (cell wall in yeasts and fungi) affect the actomyosin ring contraction. While studying the fission yeast β-glucan synthase mutantcps1-191, which is defective in division septum synthesis and actomyosin ring contraction, we found that significantly weakening of the extracellular glycan matrix caused the spheroplasts to divide at the non-permissive condition. This division was dependent on a functional actomyosin ring and vesicular trafficking, but independent of normal septum synthesis.cps1-191 cells with weakened extracellular glycan matrix divide non-medially with a much slower ring contraction rate compared to wild type cells under similar conditions, which we term as cytofission. Interestingly, the high turgor pressure appears to play minimal roles in inhibiting ring contraction incps1-191 mutants as decreasing the turgor pressure alone does not enable cytofission. We propose that during cytokinesis, the extracellular glycan matrix restricts actomyosin ring contraction and membrane ingression, and remodeling of the extracellular components through division septum synthesis relieves the inhibition and facilitates actomyosin ring contraction.
The effect of opposing notch geometry on the tensile strength of adhesively bonded single-lap joints
Authors: Çam Salim , Özel Adnan
Published: April 2020

Purpose

This study aims to investigate the effect of opposing notches formed on the adherends on the tensile strength of an adhesively bonded single-lap joint.

Design/methodology/approach

Different notch geometries were constructed on adherends and evaluated by using the Taguchi method to obtain optimum notch geometry. Then finite element analysis was conducted considering optimum notch geometries by using the cohesive zone model. Lastly, finite element analysis results were validated experimentally.

Findings

Experimental and numerical studies revealed that notches formed on adherends increased the tensile strength of the joint. The failure load of the Type-III joint, where the highest increase was observed, increased by 15 per cent. In addition, it was found that the notch shape, length, depth and distance to the overlap area had significant effects on the failure load of the joint.

Originality/value

This study shows that higher joint strengths can be accomplished by using the same joint configuration by notching adherends.
How marketing balances the battle between premium and regular products? Brand sales dynamics in an emerging market
Authors: Almeida Marcos Inácio Severo de , Porto Rafael Barreiros , Coelho Ricardo Limongi França
Published: April 2020

Purpose

Evolution and stationarity are key time series empirical concepts which need theoretical assessment by extant research. This study presents a model to explain brand sales dynamics in emerging markets using two dimensions: sales behavior in time (stationary or evolution) and final position (negative, neutral or positive).

Design/methodology/approach

A three-step methodological approach was performed. First, individual brand sales series were classified (stationarity or evolution) after unit root tests. These series were then regressed against a time variable. These two steps enabled a qualitative classification of six proposed positions, ranging from the worst to the best scenario for marketing managers. A final multinomial model identified the marketing effect to these positions.

Findings

Descriptive statistics reveal an insignificant prevalence of stationary sales series and a small number of positive brand sales series (ascending or promising). The multinomial model shows that price is negatively associated to positive brand sales positions, the important effect of service strategies and how product decisions can lead to an avoidance of negative positions.

Research limitations/implications

The model is limited to short time series of a unique transactional dataset from a multinational energy company based in Brazil.

Practical implications

The research provides a rational empirical framework to managers involved with decisions regarding brand sales dynamics in emerging markets.

Originality/value

The approach advance into the development of models to uncover conditions for market evolution and stationarity in a context marked by the shortage of data.
Information system security policy noncompliance: the role of situation-specific ethical orientation
Authors: Bansal Gaurav , Muzatko Steven , Shin Soo Il
Published: April 2020

Purpose

This study examines how neutralization strategies affect the efficacy of information system security policies. This paper proposes that neutralization strategies used to rationalize security policy noncompliance range across ethical orientations, extending from those helping the greatest number of people (ethics of care) to those damaging the fewest (ethics of justice). The results show how noncompliance differs between genders based on those ethical orientations.

Design/methodology/approach

A survey was used to measure information system security policy noncompliance intentions across six different hypothetical scenarios involving neutralization techniques used to justify noncompliance. Data was gathered from students at a mid-western, comprehensive university in the United States.

Findings

The empirical analysis suggests that gender does play a role in information system security policy noncompliance. However, its significance is dependent upon the underlying neutralization method used to justify noncompliance. The role of reward and punishment is contingent on the situation-specific ethical orientation (SSEO) which in turn is a combination of internal ethical positioning based on one's gender and external ethical reasoning based on neutralization technique.

Originality/value

This study extends ethical decision-making theory by examining how the use of punishments and rewards might be more effective in security policy compliance based upon gender. Importantly, the study emphasizes the interplay between ethics, gender and neutralization techniques, as different ethical perspectives appeal differently based on gender.
Self-efficacy, performance and the role of blended learning
Authors: Warren Liz , Reilly Dawn , Herdan Agnieszka , Lin Yong
Published: April 2020

Purpose

This paper aims to investigate the mathematics self-efficacy of students who are non-maths specialists. The project explores the student experience in the context of a maths module with a blended design, comprising both online content and face-to-face teaching. The aim was to reflect on the role of blended learning in this context.

Design/methodology/approach

Using a mixed-method analysis, the study uses data gathered via student surveys and discussion forums, as well as module grades, to provide evidence regarding whether the online component of the module enables students to master the required maths skills. The data are examined under four themes that emerged as critical to improving the self-efficacy of students: flexibility, the interactivity of the online platform, the module's blended design and the functionality of the platform.

Findings

The findings are that the blended approach increases academic self-efficacy in the area of mathematics, also enhancing the student experience. These benefits arise from the combination of allowing the individual mastery of technical skills in the private and stress-free environment provided by the online platform and access to social resources in the classroom setting.

Originality/value

The paper details the influence of self-efficacy on academic performance and the effectiveness of a blended learning approach, in the area of mathematics. It provides insight into the importance of providing multiple opportunities for students to become autonomous as they develop academic self-confidence through the mastery of maths skills.
Construction and validation of a knowledge, attitudes and practices scale related to sustainability in university students
Authors: Salas-Zapata Walter , Cardona-Arias Jaiberth Antonio
Published: April 2020

Purpose

The objective of this study was to build and validate a scale to analyze the knowledge, attitudes and practices on the sustainability of university students.

Design/methodology/approach

Psychometric validation was carried out using the criteria of internal consistency, reliability, discriminant power, content validity and predictive validity.

Findings

The KAP scale designed in this study demonstrated excellent psychometric properties and is apt for evaluating knowledge, attitudes and practices in university students.

Originality/value

Transitions toward sustainability require changes in knowledge, attitudes and practices (KAP) related to sustainability, making it necessary to have tools that support educational interventions for sustainability that tend toward a generation of changes in the decisions and behavior of people. In that sense, a KAP scale can be a useful tool to support these interventions. However, studies that use validated scales are scarce.
Peer production by persons with disabilities – opening 3D-printing aids to everybody in an inclusive MakerSpace
Authors: Bosse Ingo Karl , Pelka Bastian
Published: April 2020

Purpose

People with disabilities (PWD) produce aids using 3D printing in an inclusive MakerSpace in Germany. This study aims to demonstrate the pathways enabling people with disabilities to be “makers” of aids, creating a “medium-quality market”.

Design/methodology/approach

This study conceptualizes the foundation of the MakerSpace as a social innovation and traces supporting and hindering factors on three different layers: normative, structural and functional contexts.

Findings

3D printing can empower PWD to design and construct aids by themselves. The emerging “medium-quality” market offers potentials for availability for individualized aids. The design-thinking method used and the developed scalable approach empower PWD to create aids that best meet their own needs. The study found three arguments for printing aids that involve 3D printers: “New”: objects that are not available without a 3D printer. “Better”: objects that are available through established channels but were produced either more cheaply, quickly or on a more individualized level. “More”: objects that are available through other channels, but where 3D printing allows more of them to be produced for more people.

Research limitations/implications

The qualitative study has limitations because of sample size and context dependency. Research has only been carried out in Germany. Future research should be conducted in other countries to generalize the results.

Practical implications

The article allows to understand the emergence of a new market for aids. It can steer producers (including PWD or sheltered workshops) in producing new aids and making them available to more people.

Social implications

Understanding the functioning of the “new market for aids” can boost the accessibility of aids. Empowering PWD to produce aids can support their independence, self-determination and self-esteem. Supporting PWD to become producers of aids can support them in becoming experts and boost the quality and availability of aids.

Originality/value

All data presented has been collected by the authors.